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Filgotinib fares well in RA trial of inadequate methotrexate responders
MADRID – (cDMARD) in a phase 3 study.
The primary outcome results of the FINCH 1 study, which were presented at the European Congress of Rheumatology, showed that significantly more patients treated with filgotinib than placebo were able to achieve 20% improvement in American College of Rheumatology response criteria (ACR20).
At week 12, an ACR20 response was achieved by 69.8% of 480 patients treated with filgotinib 100 mg/day, 76.6% of 475 treated with filgotinib 200 mg/day, and 49.9% of 475 given a matching daily placebo (P less than .0001 for both comparisons). Adalimumab (Humira; 40 mg every 2 weeks) was used as an active comparator in the trial, and 70.8% of 325 patients treated with this biologic drug achieved an ACR20.
Similar patterns were seen for the ACR50 and ACR70 responses: more than 50% of patients treated with filgotinib or adalimumab achieved an ACR50 versus 33.3% of patients treated with placebo. The ACR70 response rate was more than 30% in patients treated with either biologic, compared against 14.9% with placebo.
The percentages of patients in the filgotinib 100-mg, filgotinib 200-mg, adalimumab, and placebo arms who achieved a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or less at 12 weeks were 38.8%, 49.9%, 43.4%, and 23.4%. At 24 weeks, the rates were 53.1%, 60.6%, 50.5%, and 33.7%.
At 12 weeks, analysis showed that filgotinib 200 mg was noninferior to adalimumab in achieving a DAS28-CRP of 3.2 or less.
These study data, together with the results of two other phase 3 studies – FINCH 2 and FINCH 3 – will be used to submit a new drug application to the Food and Drug Administration for the use of filgotinib in the treatment of RA later this year, the drug’s developer, Gilead Sciences, announced on July 1. Each of the trials has addressed a different population of RA patients; while FINCH 1 looked at inadequate responders to methotrexate, FINCH 2 looked at those with an inadequate response to biologic DMARDs, and FINCH 3 recruited RA patients who were naive to methotrexate therapy.
FINCH 1 was a 1-year study, said presenting study investigator Bernard Combe, MD, PhD, professor of rheumatology at Montpellier (France) University and head of the bone and joint diseases department at the university. A total of 1,759 patients were randomized and 1,755 received study treatment with filgotinib, adalimumab, or placebo in addition to methotrexate. Data for the first 24 weeks were presented.
Dr. Combe and coauthors used hierarchical statistical testing to first compare the 200-mg dose versus placebo for the primary endpoint, and then, if positive, the percentage of patients at 12 weeks achieving a DAS28-CRP score of 3.2 or less and the score at 12 weeks on the Health Assessment Questionnaire – Disability Index (HAQ-DI), and then the DAS28-CRP again at 24 weeks. This was repeated with the 100-mg dose until finally noninferiority of the 200-mg dose versus adalimumab in DAS28-CRP at 12 weeks was tested.
Other findings included a significant reduction in radiographic progression at week 24 with both doses of filgotinib versus placebo; improvements in HAQ-DI and Functional Assessment of Chronic Illness Therapy-Fatigue scores also were seen at 12 and 24 weeks.
“The selective JAK1 inhibitor filgotinib, at doses of 200 and 100 mg per day, led to significant improvement in symptoms of RA patients with inadequate response to methotrexate,” Dr. Combe concluded. It “prevented radiographic progression, and improved physical function compared to placebo.”
Importantly, the drug was “well tolerated” and “a low frequency of venous thrombotic events, serious infections, and other adverse events of interest was observed.”
Commenting on the study during the Q&A session that followed Dr. Combe’s presentation, Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas, noted that the choice of DAS28-CRP was “very unusual” as an endpoint after the ACR20 as it’s “almost always an ACR50 or 70.” There was also a “very high placebo response.”
Dr. Combe responded that he “wasn’t so surprised by the high placebo response. You know that this has been shown previously in some other trials.” As to why, he noted that there was an ongoing analysis but also proposed two reasons: First, the geographic region – with more than 1,700 patients from all over the world included in the trial, there could be variation in the placebo responses. Second, methotrexate might still be having a minor effect when the trial started.
The study was sponsored by Gilead Sciences in collaboration with Galapagos NV. Dr. Combe has received honoraria from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Sun Pharma Advanced Research, Boehringer Ingelheim, and Flexion. Dr. Combe is a shareholder in Novartis.
SOURCE: Combe B et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-8. Abstract LB0001, doi: 10.1136/annrheumdis-2019-eular.8676
MADRID – (cDMARD) in a phase 3 study.
The primary outcome results of the FINCH 1 study, which were presented at the European Congress of Rheumatology, showed that significantly more patients treated with filgotinib than placebo were able to achieve 20% improvement in American College of Rheumatology response criteria (ACR20).
At week 12, an ACR20 response was achieved by 69.8% of 480 patients treated with filgotinib 100 mg/day, 76.6% of 475 treated with filgotinib 200 mg/day, and 49.9% of 475 given a matching daily placebo (P less than .0001 for both comparisons). Adalimumab (Humira; 40 mg every 2 weeks) was used as an active comparator in the trial, and 70.8% of 325 patients treated with this biologic drug achieved an ACR20.
Similar patterns were seen for the ACR50 and ACR70 responses: more than 50% of patients treated with filgotinib or adalimumab achieved an ACR50 versus 33.3% of patients treated with placebo. The ACR70 response rate was more than 30% in patients treated with either biologic, compared against 14.9% with placebo.
The percentages of patients in the filgotinib 100-mg, filgotinib 200-mg, adalimumab, and placebo arms who achieved a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or less at 12 weeks were 38.8%, 49.9%, 43.4%, and 23.4%. At 24 weeks, the rates were 53.1%, 60.6%, 50.5%, and 33.7%.
At 12 weeks, analysis showed that filgotinib 200 mg was noninferior to adalimumab in achieving a DAS28-CRP of 3.2 or less.
These study data, together with the results of two other phase 3 studies – FINCH 2 and FINCH 3 – will be used to submit a new drug application to the Food and Drug Administration for the use of filgotinib in the treatment of RA later this year, the drug’s developer, Gilead Sciences, announced on July 1. Each of the trials has addressed a different population of RA patients; while FINCH 1 looked at inadequate responders to methotrexate, FINCH 2 looked at those with an inadequate response to biologic DMARDs, and FINCH 3 recruited RA patients who were naive to methotrexate therapy.
FINCH 1 was a 1-year study, said presenting study investigator Bernard Combe, MD, PhD, professor of rheumatology at Montpellier (France) University and head of the bone and joint diseases department at the university. A total of 1,759 patients were randomized and 1,755 received study treatment with filgotinib, adalimumab, or placebo in addition to methotrexate. Data for the first 24 weeks were presented.
Dr. Combe and coauthors used hierarchical statistical testing to first compare the 200-mg dose versus placebo for the primary endpoint, and then, if positive, the percentage of patients at 12 weeks achieving a DAS28-CRP score of 3.2 or less and the score at 12 weeks on the Health Assessment Questionnaire – Disability Index (HAQ-DI), and then the DAS28-CRP again at 24 weeks. This was repeated with the 100-mg dose until finally noninferiority of the 200-mg dose versus adalimumab in DAS28-CRP at 12 weeks was tested.
Other findings included a significant reduction in radiographic progression at week 24 with both doses of filgotinib versus placebo; improvements in HAQ-DI and Functional Assessment of Chronic Illness Therapy-Fatigue scores also were seen at 12 and 24 weeks.
“The selective JAK1 inhibitor filgotinib, at doses of 200 and 100 mg per day, led to significant improvement in symptoms of RA patients with inadequate response to methotrexate,” Dr. Combe concluded. It “prevented radiographic progression, and improved physical function compared to placebo.”
Importantly, the drug was “well tolerated” and “a low frequency of venous thrombotic events, serious infections, and other adverse events of interest was observed.”
Commenting on the study during the Q&A session that followed Dr. Combe’s presentation, Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas, noted that the choice of DAS28-CRP was “very unusual” as an endpoint after the ACR20 as it’s “almost always an ACR50 or 70.” There was also a “very high placebo response.”
Dr. Combe responded that he “wasn’t so surprised by the high placebo response. You know that this has been shown previously in some other trials.” As to why, he noted that there was an ongoing analysis but also proposed two reasons: First, the geographic region – with more than 1,700 patients from all over the world included in the trial, there could be variation in the placebo responses. Second, methotrexate might still be having a minor effect when the trial started.
The study was sponsored by Gilead Sciences in collaboration with Galapagos NV. Dr. Combe has received honoraria from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Sun Pharma Advanced Research, Boehringer Ingelheim, and Flexion. Dr. Combe is a shareholder in Novartis.
SOURCE: Combe B et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-8. Abstract LB0001, doi: 10.1136/annrheumdis-2019-eular.8676
MADRID – (cDMARD) in a phase 3 study.
The primary outcome results of the FINCH 1 study, which were presented at the European Congress of Rheumatology, showed that significantly more patients treated with filgotinib than placebo were able to achieve 20% improvement in American College of Rheumatology response criteria (ACR20).
At week 12, an ACR20 response was achieved by 69.8% of 480 patients treated with filgotinib 100 mg/day, 76.6% of 475 treated with filgotinib 200 mg/day, and 49.9% of 475 given a matching daily placebo (P less than .0001 for both comparisons). Adalimumab (Humira; 40 mg every 2 weeks) was used as an active comparator in the trial, and 70.8% of 325 patients treated with this biologic drug achieved an ACR20.
Similar patterns were seen for the ACR50 and ACR70 responses: more than 50% of patients treated with filgotinib or adalimumab achieved an ACR50 versus 33.3% of patients treated with placebo. The ACR70 response rate was more than 30% in patients treated with either biologic, compared against 14.9% with placebo.
The percentages of patients in the filgotinib 100-mg, filgotinib 200-mg, adalimumab, and placebo arms who achieved a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or less at 12 weeks were 38.8%, 49.9%, 43.4%, and 23.4%. At 24 weeks, the rates were 53.1%, 60.6%, 50.5%, and 33.7%.
At 12 weeks, analysis showed that filgotinib 200 mg was noninferior to adalimumab in achieving a DAS28-CRP of 3.2 or less.
These study data, together with the results of two other phase 3 studies – FINCH 2 and FINCH 3 – will be used to submit a new drug application to the Food and Drug Administration for the use of filgotinib in the treatment of RA later this year, the drug’s developer, Gilead Sciences, announced on July 1. Each of the trials has addressed a different population of RA patients; while FINCH 1 looked at inadequate responders to methotrexate, FINCH 2 looked at those with an inadequate response to biologic DMARDs, and FINCH 3 recruited RA patients who were naive to methotrexate therapy.
FINCH 1 was a 1-year study, said presenting study investigator Bernard Combe, MD, PhD, professor of rheumatology at Montpellier (France) University and head of the bone and joint diseases department at the university. A total of 1,759 patients were randomized and 1,755 received study treatment with filgotinib, adalimumab, or placebo in addition to methotrexate. Data for the first 24 weeks were presented.
Dr. Combe and coauthors used hierarchical statistical testing to first compare the 200-mg dose versus placebo for the primary endpoint, and then, if positive, the percentage of patients at 12 weeks achieving a DAS28-CRP score of 3.2 or less and the score at 12 weeks on the Health Assessment Questionnaire – Disability Index (HAQ-DI), and then the DAS28-CRP again at 24 weeks. This was repeated with the 100-mg dose until finally noninferiority of the 200-mg dose versus adalimumab in DAS28-CRP at 12 weeks was tested.
Other findings included a significant reduction in radiographic progression at week 24 with both doses of filgotinib versus placebo; improvements in HAQ-DI and Functional Assessment of Chronic Illness Therapy-Fatigue scores also were seen at 12 and 24 weeks.
“The selective JAK1 inhibitor filgotinib, at doses of 200 and 100 mg per day, led to significant improvement in symptoms of RA patients with inadequate response to methotrexate,” Dr. Combe concluded. It “prevented radiographic progression, and improved physical function compared to placebo.”
Importantly, the drug was “well tolerated” and “a low frequency of venous thrombotic events, serious infections, and other adverse events of interest was observed.”
Commenting on the study during the Q&A session that followed Dr. Combe’s presentation, Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas, noted that the choice of DAS28-CRP was “very unusual” as an endpoint after the ACR20 as it’s “almost always an ACR50 or 70.” There was also a “very high placebo response.”
Dr. Combe responded that he “wasn’t so surprised by the high placebo response. You know that this has been shown previously in some other trials.” As to why, he noted that there was an ongoing analysis but also proposed two reasons: First, the geographic region – with more than 1,700 patients from all over the world included in the trial, there could be variation in the placebo responses. Second, methotrexate might still be having a minor effect when the trial started.
The study was sponsored by Gilead Sciences in collaboration with Galapagos NV. Dr. Combe has received honoraria from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Sun Pharma Advanced Research, Boehringer Ingelheim, and Flexion. Dr. Combe is a shareholder in Novartis.
SOURCE: Combe B et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-8. Abstract LB0001, doi: 10.1136/annrheumdis-2019-eular.8676
REPORTING FROM EULAR 2019 CONGRESS
First adult APS recommendations released by European society
MADRID – Low-dose aspirin is recommended for the primary prevention of antiphospholipid syndrome (APS) in patients at high risk for developing the condition, according to new recommendations developed by the European League Against Rheumatism (EULAR).
Indeed, the NSAID should be given at a dose of between 75 mg and 100 mg per day, in patients with a “high risk” antiphospholipid (aPL) antibody profile, including asymptomatic aPL antibody carriers, patients with systemic lupus erythematosus (SLE) without APS, and in women who are not pregnant but who have a history of obstetric APS.
The recommendations aim to help guide practice and ultimately to improve the quality of care for patients and their outcomes following treatment, Maria G. Tektonidou, MD, PhD, said at the European Congress of Rheumatology.
The guidance is necessary as “clinical practice in APS remains highly variable,” said Dr. Tektonidou of the National and Kapodistrian University of Athens. This is perhaps because APS is a “rare disease and also because it’s a newly recognized disease – it’s only 35 years old – and knowledge about the clinical spectrum, classification, and management is continuously advancing.”
Dr. Tektonidou, who was the convener of the EULAR Task Force that wrote the recommendations, noted that they were now published in Annals of the Rheumatic Diseases and considered three main groups of patients: those with thrombotic APS, those with obstetric APS, and those with catastrophic APS (CAPS). There are three overarching principles, 12 recommendations, and 29 graded statements, she said.
The three overarching principles concerned risk stratification, general measures for managing patients who test positive for aPL antibodies, and patient education and counseling on various topics, such as treatment adherence, therapeutic drug monitoring, contraceptive use, and lifestyle interventions.
Dr. Tektonidou highlighted how risk stratification was important and that a high-risk aPL profile was defined as the presence of lupus anticoagulant (LA) on at least two occasions, measured 12 weeks apart according to International Society on Thrombosis and Haemostasis guidelines, or the presence of two or even three aPL antibodies, or persistently high aPL antibody titers. By contrast, a low-risk aPL profile was defined as the isolated presence of anticardiolipin (aCL) or anti–beta-2 glycoprotein I antibodies at low-medium titers, particularly if transiently positive.
“Risk stratification should include the determination of the high-risk aPL profile; a prior history of thrombotic or obstetric [APS]; the coexistence of other systemic autoimmune diseases, and the presence of traditional cardiovascular risk factors,” Dr. Tektonidou said.
Four of the recommendations focus on the secondary prevention of APS, giving guidance on anticoagulant treatment with definite APS, first provoked or unprovoked venous thrombosis, and how to manage recurrent venous thrombosis. There also is a recommendation for the management of patients with definite APS and a first arterial thrombosis, outlining the type and intensity of anticoagulant therapy that should be given. Another four of the recommendations focus on the management of obstetric APS, with a focus on how to manage the various types of complications seen in pregnant women. Then the final recommendation concerns CAPS, it’s prevention and first-line treatment, and how to manage refractory patients.
With regards to CAPS, Ricard Cervera, MD, PhD, of the Hospital Clinic of Barcelona, this is “terrible” but “thankfully rare” form of APS that was first described in the early 1990s.
Although fewer than 1% of the APS adult population have CAPS (Arthritis Rheum. 2002;46[4]:1019-27), it’s a condition in which several thrombotic events occur simultaneously, affecting multiple systems or organs and which can be life threatening if not treated quickly.
New treatment guidelines for catastrophic APS
During a separate clinical science session at the conference, Dr. Cervera discussed the development of treatment guidelines for CAPS, noting that this had been one of the focus points of the McMaster RARE-Bestpractices project group in 2016. The group selected CAPS for a pilot exercise in guideline development for a rare disease and published their recommendations in 2018 (J Thromb Haemost. 2018;16:1656-64). Ten recommendations were developed, most of which were conditional, Dr. Cervera said, due to the lack of, or very low certainty, of the evidence.
The new EULAR 2019 adult APS recommendations now include CAPS and recommendation number 12 is split into two parts. The first, part A, states that prompt treatment of infections is needed in all patients positive for aPL antibodies and that anticoagulation should have minimal interruption or be used at level to help prevent the development of CAPS.
The second, part B, states that the first-line treatment of CAPS should be a triple combination therapy of glucocorticoids, heparin, and plasma exchange, or intravenous immunoglobulins, rather than single-agent treatment. Plus, it says that any triggering factor should be treated accordingly.
“Finally,” Dr. Cervera said, “in patients with refractory CAPS, B-cell depletion with rituximab or complement inhibitors, for example eculizumab, may be considered.”
The adult APS recommendations project was funded by EULAR. Dr. Tektonidou and Dr. Cervera reported having no relevant conflicts of interest.
SOURCES: Tektonidou M. Ann Rheum Dis. Jun 2019;78(Suppl 2):59-60. Abstract SP0191, doi: 0.1136/annrheumdis-2019-eular.8601; and Cervera R et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):62. Abstract SP0201. doi: 10.1136/annrheumdis-2019-eular.8444.
MADRID – Low-dose aspirin is recommended for the primary prevention of antiphospholipid syndrome (APS) in patients at high risk for developing the condition, according to new recommendations developed by the European League Against Rheumatism (EULAR).
Indeed, the NSAID should be given at a dose of between 75 mg and 100 mg per day, in patients with a “high risk” antiphospholipid (aPL) antibody profile, including asymptomatic aPL antibody carriers, patients with systemic lupus erythematosus (SLE) without APS, and in women who are not pregnant but who have a history of obstetric APS.
The recommendations aim to help guide practice and ultimately to improve the quality of care for patients and their outcomes following treatment, Maria G. Tektonidou, MD, PhD, said at the European Congress of Rheumatology.
The guidance is necessary as “clinical practice in APS remains highly variable,” said Dr. Tektonidou of the National and Kapodistrian University of Athens. This is perhaps because APS is a “rare disease and also because it’s a newly recognized disease – it’s only 35 years old – and knowledge about the clinical spectrum, classification, and management is continuously advancing.”
Dr. Tektonidou, who was the convener of the EULAR Task Force that wrote the recommendations, noted that they were now published in Annals of the Rheumatic Diseases and considered three main groups of patients: those with thrombotic APS, those with obstetric APS, and those with catastrophic APS (CAPS). There are three overarching principles, 12 recommendations, and 29 graded statements, she said.
The three overarching principles concerned risk stratification, general measures for managing patients who test positive for aPL antibodies, and patient education and counseling on various topics, such as treatment adherence, therapeutic drug monitoring, contraceptive use, and lifestyle interventions.
Dr. Tektonidou highlighted how risk stratification was important and that a high-risk aPL profile was defined as the presence of lupus anticoagulant (LA) on at least two occasions, measured 12 weeks apart according to International Society on Thrombosis and Haemostasis guidelines, or the presence of two or even three aPL antibodies, or persistently high aPL antibody titers. By contrast, a low-risk aPL profile was defined as the isolated presence of anticardiolipin (aCL) or anti–beta-2 glycoprotein I antibodies at low-medium titers, particularly if transiently positive.
“Risk stratification should include the determination of the high-risk aPL profile; a prior history of thrombotic or obstetric [APS]; the coexistence of other systemic autoimmune diseases, and the presence of traditional cardiovascular risk factors,” Dr. Tektonidou said.
Four of the recommendations focus on the secondary prevention of APS, giving guidance on anticoagulant treatment with definite APS, first provoked or unprovoked venous thrombosis, and how to manage recurrent venous thrombosis. There also is a recommendation for the management of patients with definite APS and a first arterial thrombosis, outlining the type and intensity of anticoagulant therapy that should be given. Another four of the recommendations focus on the management of obstetric APS, with a focus on how to manage the various types of complications seen in pregnant women. Then the final recommendation concerns CAPS, it’s prevention and first-line treatment, and how to manage refractory patients.
With regards to CAPS, Ricard Cervera, MD, PhD, of the Hospital Clinic of Barcelona, this is “terrible” but “thankfully rare” form of APS that was first described in the early 1990s.
Although fewer than 1% of the APS adult population have CAPS (Arthritis Rheum. 2002;46[4]:1019-27), it’s a condition in which several thrombotic events occur simultaneously, affecting multiple systems or organs and which can be life threatening if not treated quickly.
New treatment guidelines for catastrophic APS
During a separate clinical science session at the conference, Dr. Cervera discussed the development of treatment guidelines for CAPS, noting that this had been one of the focus points of the McMaster RARE-Bestpractices project group in 2016. The group selected CAPS for a pilot exercise in guideline development for a rare disease and published their recommendations in 2018 (J Thromb Haemost. 2018;16:1656-64). Ten recommendations were developed, most of which were conditional, Dr. Cervera said, due to the lack of, or very low certainty, of the evidence.
The new EULAR 2019 adult APS recommendations now include CAPS and recommendation number 12 is split into two parts. The first, part A, states that prompt treatment of infections is needed in all patients positive for aPL antibodies and that anticoagulation should have minimal interruption or be used at level to help prevent the development of CAPS.
The second, part B, states that the first-line treatment of CAPS should be a triple combination therapy of glucocorticoids, heparin, and plasma exchange, or intravenous immunoglobulins, rather than single-agent treatment. Plus, it says that any triggering factor should be treated accordingly.
“Finally,” Dr. Cervera said, “in patients with refractory CAPS, B-cell depletion with rituximab or complement inhibitors, for example eculizumab, may be considered.”
The adult APS recommendations project was funded by EULAR. Dr. Tektonidou and Dr. Cervera reported having no relevant conflicts of interest.
SOURCES: Tektonidou M. Ann Rheum Dis. Jun 2019;78(Suppl 2):59-60. Abstract SP0191, doi: 0.1136/annrheumdis-2019-eular.8601; and Cervera R et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):62. Abstract SP0201. doi: 10.1136/annrheumdis-2019-eular.8444.
MADRID – Low-dose aspirin is recommended for the primary prevention of antiphospholipid syndrome (APS) in patients at high risk for developing the condition, according to new recommendations developed by the European League Against Rheumatism (EULAR).
Indeed, the NSAID should be given at a dose of between 75 mg and 100 mg per day, in patients with a “high risk” antiphospholipid (aPL) antibody profile, including asymptomatic aPL antibody carriers, patients with systemic lupus erythematosus (SLE) without APS, and in women who are not pregnant but who have a history of obstetric APS.
The recommendations aim to help guide practice and ultimately to improve the quality of care for patients and their outcomes following treatment, Maria G. Tektonidou, MD, PhD, said at the European Congress of Rheumatology.
The guidance is necessary as “clinical practice in APS remains highly variable,” said Dr. Tektonidou of the National and Kapodistrian University of Athens. This is perhaps because APS is a “rare disease and also because it’s a newly recognized disease – it’s only 35 years old – and knowledge about the clinical spectrum, classification, and management is continuously advancing.”
Dr. Tektonidou, who was the convener of the EULAR Task Force that wrote the recommendations, noted that they were now published in Annals of the Rheumatic Diseases and considered three main groups of patients: those with thrombotic APS, those with obstetric APS, and those with catastrophic APS (CAPS). There are three overarching principles, 12 recommendations, and 29 graded statements, she said.
The three overarching principles concerned risk stratification, general measures for managing patients who test positive for aPL antibodies, and patient education and counseling on various topics, such as treatment adherence, therapeutic drug monitoring, contraceptive use, and lifestyle interventions.
Dr. Tektonidou highlighted how risk stratification was important and that a high-risk aPL profile was defined as the presence of lupus anticoagulant (LA) on at least two occasions, measured 12 weeks apart according to International Society on Thrombosis and Haemostasis guidelines, or the presence of two or even three aPL antibodies, or persistently high aPL antibody titers. By contrast, a low-risk aPL profile was defined as the isolated presence of anticardiolipin (aCL) or anti–beta-2 glycoprotein I antibodies at low-medium titers, particularly if transiently positive.
“Risk stratification should include the determination of the high-risk aPL profile; a prior history of thrombotic or obstetric [APS]; the coexistence of other systemic autoimmune diseases, and the presence of traditional cardiovascular risk factors,” Dr. Tektonidou said.
Four of the recommendations focus on the secondary prevention of APS, giving guidance on anticoagulant treatment with definite APS, first provoked or unprovoked venous thrombosis, and how to manage recurrent venous thrombosis. There also is a recommendation for the management of patients with definite APS and a first arterial thrombosis, outlining the type and intensity of anticoagulant therapy that should be given. Another four of the recommendations focus on the management of obstetric APS, with a focus on how to manage the various types of complications seen in pregnant women. Then the final recommendation concerns CAPS, it’s prevention and first-line treatment, and how to manage refractory patients.
With regards to CAPS, Ricard Cervera, MD, PhD, of the Hospital Clinic of Barcelona, this is “terrible” but “thankfully rare” form of APS that was first described in the early 1990s.
Although fewer than 1% of the APS adult population have CAPS (Arthritis Rheum. 2002;46[4]:1019-27), it’s a condition in which several thrombotic events occur simultaneously, affecting multiple systems or organs and which can be life threatening if not treated quickly.
New treatment guidelines for catastrophic APS
During a separate clinical science session at the conference, Dr. Cervera discussed the development of treatment guidelines for CAPS, noting that this had been one of the focus points of the McMaster RARE-Bestpractices project group in 2016. The group selected CAPS for a pilot exercise in guideline development for a rare disease and published their recommendations in 2018 (J Thromb Haemost. 2018;16:1656-64). Ten recommendations were developed, most of which were conditional, Dr. Cervera said, due to the lack of, or very low certainty, of the evidence.
The new EULAR 2019 adult APS recommendations now include CAPS and recommendation number 12 is split into two parts. The first, part A, states that prompt treatment of infections is needed in all patients positive for aPL antibodies and that anticoagulation should have minimal interruption or be used at level to help prevent the development of CAPS.
The second, part B, states that the first-line treatment of CAPS should be a triple combination therapy of glucocorticoids, heparin, and plasma exchange, or intravenous immunoglobulins, rather than single-agent treatment. Plus, it says that any triggering factor should be treated accordingly.
“Finally,” Dr. Cervera said, “in patients with refractory CAPS, B-cell depletion with rituximab or complement inhibitors, for example eculizumab, may be considered.”
The adult APS recommendations project was funded by EULAR. Dr. Tektonidou and Dr. Cervera reported having no relevant conflicts of interest.
SOURCES: Tektonidou M. Ann Rheum Dis. Jun 2019;78(Suppl 2):59-60. Abstract SP0191, doi: 0.1136/annrheumdis-2019-eular.8601; and Cervera R et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):62. Abstract SP0201. doi: 10.1136/annrheumdis-2019-eular.8444.
REPORTING FROM THE EULAR 2019 Congress
Abatacept response in seropositive RA may be linked to HLA gene
MADRID – according to results from the “exploratory” Early AMPLE study.
Clinical responses seen in the study were higher in the abatacept (Orencia) versus adalimumab group, study investigator Vivian P. Bykerk, MD, reported at the European Congress of Rheumatology. Indeed, a 20% improvement in American College of Rheumatology response criteria (ACR20), as well as ACR50 and ACR70 responses, were achieved by 83%, 70%, and 48% of abatacept-treated patients and by 63%, 45%, and 30% of adalimumab-treated patients.
Numerically higher percentages of patients who were treated with abatacept and had the shared epitope in the human leukocyte antigen (HLA) DRB1 (HLA-DRB1) allele achieved ACR20-level improvement when compared against treatment with adalimumab, and the same was seen for ACR50 and ACR70 response rates.
“The results we saw were clearly driven by the presence of the shared epitope, and there may be a differential benefit by treating the shared epitope in early RA patients with abatacept, compared with adalimumab,” said Dr. Bykerk, who is director of the Inflammatory Arthritis Center of Excellence at the Hospital for Special Surgery in New York.
The investigators also observed numerically higher responses on the Simplified Disease Activity Index and Clinical Disease Activity Index as well as the 28-joint Disease Activity Score using C-reactive protein.
The shared epitope is a major histocompatibility complex (MHC) class II protein receptor encoded by some alleles of the HLA-DRB1 gene. It’s found in the majority (70%–80%) of RA patients who are seropositive for anti-citrullinated protein antibodies (ACPAs), and it’s linked to joint destruction.
Prior work has suggested that abatacept may be more effective in RA patients who have the shared epitope than in those who do not, Dr. Bykerk explained.
Early AMPLE (Abatacept versus adalimumab comparison in biologic naive RA subjects with background methotrexate) was a prospective, randomized, single-blind, controlled study that ran for 24 weeks. It’s aim was to look at changes in immune cells and proteins in response to treatment with abatacept and adalimumab, which were both given in combination with methotrexate, and in relation to the presence or absence of the shared epitope.
Since abatacept works directly on T-cell activation, the investigators hypothesized that it should have a greater effect than other agents that work further downstream, such as the tumor necrosis factor (TNF) inhibitor adalimumab.
A total of 80 patients who had RA for less than 1 year and had not previously been treated with a biologic were recruited; all were positive for ACPA, specifically anti–cyclic citrullinated protein 2 (anti-CCP2) antibodies, and 76% had the shared epitope.
“Of note, we observed higher ACPA levels in the shared epitope group, and this requires further observation and understanding,” Dr. Bykerk said. The mean level of anti-CCP2 antibodies in patients with and without the shared epitope were a respective 1,216 U/mL and 368 U/mL.
Patients had been randomized 1:1 to receive either abatacept (125 mg given subcutaneously every week) or adalimumab (40 mg given subcutaneously every 2 weeks) on top of continuing weekly treatment with oral methotrexate.
“For a long time, we’ve wanted to try to match a therapy’s mechanism of action to what’s going on with the patient,” Dr. Bykerk commented in an interview. “Clinical phenotyping is usually not good enough, and we are always guessing,” she added. Plus, she noted, RA treatments tend to be used in the order in which they were approved rather than there being a rationale for using one over another based on their suitability in a particular situation.
The Early AMPLE data “are a first step towards the rational choice of therapy that might be more likely to be sustainable in a patient for a longer period of time and actually continue to modify the disease,” Dr. Bykerk suggested.
TNF inhibitors “work across the board in early disease,” she observed. “The problem is that after a year or two that only 44% of people are left on their first TNF, and why is that?” Reasons for the loss of effect are not known. Using a drug that works in a different way might prove to be the answer, such as seen here with abatacept in seropositive patients with the shared episode, but further studies will be needed to validate the Early AMPLE findings.
Bristol-Myers Squibb sponsored the study. Dr. Bykerk disclosed receiving grant or research support paid to her institution from BMS, as well as Amgen and UCB. She also disclosed acting as a consultant to BMS and multiple other pharmaceutical companies. Several coauthors were employees and shareholders in BMS, or had acted as consultants to BMS.
SOURCE: Rigby W et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):263-4. Abstract LB0008 , doi: 10.1136/annrheumdis-2019-eular.8668.
MADRID – according to results from the “exploratory” Early AMPLE study.
Clinical responses seen in the study were higher in the abatacept (Orencia) versus adalimumab group, study investigator Vivian P. Bykerk, MD, reported at the European Congress of Rheumatology. Indeed, a 20% improvement in American College of Rheumatology response criteria (ACR20), as well as ACR50 and ACR70 responses, were achieved by 83%, 70%, and 48% of abatacept-treated patients and by 63%, 45%, and 30% of adalimumab-treated patients.
Numerically higher percentages of patients who were treated with abatacept and had the shared epitope in the human leukocyte antigen (HLA) DRB1 (HLA-DRB1) allele achieved ACR20-level improvement when compared against treatment with adalimumab, and the same was seen for ACR50 and ACR70 response rates.
“The results we saw were clearly driven by the presence of the shared epitope, and there may be a differential benefit by treating the shared epitope in early RA patients with abatacept, compared with adalimumab,” said Dr. Bykerk, who is director of the Inflammatory Arthritis Center of Excellence at the Hospital for Special Surgery in New York.
The investigators also observed numerically higher responses on the Simplified Disease Activity Index and Clinical Disease Activity Index as well as the 28-joint Disease Activity Score using C-reactive protein.
The shared epitope is a major histocompatibility complex (MHC) class II protein receptor encoded by some alleles of the HLA-DRB1 gene. It’s found in the majority (70%–80%) of RA patients who are seropositive for anti-citrullinated protein antibodies (ACPAs), and it’s linked to joint destruction.
Prior work has suggested that abatacept may be more effective in RA patients who have the shared epitope than in those who do not, Dr. Bykerk explained.
Early AMPLE (Abatacept versus adalimumab comparison in biologic naive RA subjects with background methotrexate) was a prospective, randomized, single-blind, controlled study that ran for 24 weeks. It’s aim was to look at changes in immune cells and proteins in response to treatment with abatacept and adalimumab, which were both given in combination with methotrexate, and in relation to the presence or absence of the shared epitope.
Since abatacept works directly on T-cell activation, the investigators hypothesized that it should have a greater effect than other agents that work further downstream, such as the tumor necrosis factor (TNF) inhibitor adalimumab.
A total of 80 patients who had RA for less than 1 year and had not previously been treated with a biologic were recruited; all were positive for ACPA, specifically anti–cyclic citrullinated protein 2 (anti-CCP2) antibodies, and 76% had the shared epitope.
“Of note, we observed higher ACPA levels in the shared epitope group, and this requires further observation and understanding,” Dr. Bykerk said. The mean level of anti-CCP2 antibodies in patients with and without the shared epitope were a respective 1,216 U/mL and 368 U/mL.
Patients had been randomized 1:1 to receive either abatacept (125 mg given subcutaneously every week) or adalimumab (40 mg given subcutaneously every 2 weeks) on top of continuing weekly treatment with oral methotrexate.
“For a long time, we’ve wanted to try to match a therapy’s mechanism of action to what’s going on with the patient,” Dr. Bykerk commented in an interview. “Clinical phenotyping is usually not good enough, and we are always guessing,” she added. Plus, she noted, RA treatments tend to be used in the order in which they were approved rather than there being a rationale for using one over another based on their suitability in a particular situation.
The Early AMPLE data “are a first step towards the rational choice of therapy that might be more likely to be sustainable in a patient for a longer period of time and actually continue to modify the disease,” Dr. Bykerk suggested.
TNF inhibitors “work across the board in early disease,” she observed. “The problem is that after a year or two that only 44% of people are left on their first TNF, and why is that?” Reasons for the loss of effect are not known. Using a drug that works in a different way might prove to be the answer, such as seen here with abatacept in seropositive patients with the shared episode, but further studies will be needed to validate the Early AMPLE findings.
Bristol-Myers Squibb sponsored the study. Dr. Bykerk disclosed receiving grant or research support paid to her institution from BMS, as well as Amgen and UCB. She also disclosed acting as a consultant to BMS and multiple other pharmaceutical companies. Several coauthors were employees and shareholders in BMS, or had acted as consultants to BMS.
SOURCE: Rigby W et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):263-4. Abstract LB0008 , doi: 10.1136/annrheumdis-2019-eular.8668.
MADRID – according to results from the “exploratory” Early AMPLE study.
Clinical responses seen in the study were higher in the abatacept (Orencia) versus adalimumab group, study investigator Vivian P. Bykerk, MD, reported at the European Congress of Rheumatology. Indeed, a 20% improvement in American College of Rheumatology response criteria (ACR20), as well as ACR50 and ACR70 responses, were achieved by 83%, 70%, and 48% of abatacept-treated patients and by 63%, 45%, and 30% of adalimumab-treated patients.
Numerically higher percentages of patients who were treated with abatacept and had the shared epitope in the human leukocyte antigen (HLA) DRB1 (HLA-DRB1) allele achieved ACR20-level improvement when compared against treatment with adalimumab, and the same was seen for ACR50 and ACR70 response rates.
“The results we saw were clearly driven by the presence of the shared epitope, and there may be a differential benefit by treating the shared epitope in early RA patients with abatacept, compared with adalimumab,” said Dr. Bykerk, who is director of the Inflammatory Arthritis Center of Excellence at the Hospital for Special Surgery in New York.
The investigators also observed numerically higher responses on the Simplified Disease Activity Index and Clinical Disease Activity Index as well as the 28-joint Disease Activity Score using C-reactive protein.
The shared epitope is a major histocompatibility complex (MHC) class II protein receptor encoded by some alleles of the HLA-DRB1 gene. It’s found in the majority (70%–80%) of RA patients who are seropositive for anti-citrullinated protein antibodies (ACPAs), and it’s linked to joint destruction.
Prior work has suggested that abatacept may be more effective in RA patients who have the shared epitope than in those who do not, Dr. Bykerk explained.
Early AMPLE (Abatacept versus adalimumab comparison in biologic naive RA subjects with background methotrexate) was a prospective, randomized, single-blind, controlled study that ran for 24 weeks. It’s aim was to look at changes in immune cells and proteins in response to treatment with abatacept and adalimumab, which were both given in combination with methotrexate, and in relation to the presence or absence of the shared epitope.
Since abatacept works directly on T-cell activation, the investigators hypothesized that it should have a greater effect than other agents that work further downstream, such as the tumor necrosis factor (TNF) inhibitor adalimumab.
A total of 80 patients who had RA for less than 1 year and had not previously been treated with a biologic were recruited; all were positive for ACPA, specifically anti–cyclic citrullinated protein 2 (anti-CCP2) antibodies, and 76% had the shared epitope.
“Of note, we observed higher ACPA levels in the shared epitope group, and this requires further observation and understanding,” Dr. Bykerk said. The mean level of anti-CCP2 antibodies in patients with and without the shared epitope were a respective 1,216 U/mL and 368 U/mL.
Patients had been randomized 1:1 to receive either abatacept (125 mg given subcutaneously every week) or adalimumab (40 mg given subcutaneously every 2 weeks) on top of continuing weekly treatment with oral methotrexate.
“For a long time, we’ve wanted to try to match a therapy’s mechanism of action to what’s going on with the patient,” Dr. Bykerk commented in an interview. “Clinical phenotyping is usually not good enough, and we are always guessing,” she added. Plus, she noted, RA treatments tend to be used in the order in which they were approved rather than there being a rationale for using one over another based on their suitability in a particular situation.
The Early AMPLE data “are a first step towards the rational choice of therapy that might be more likely to be sustainable in a patient for a longer period of time and actually continue to modify the disease,” Dr. Bykerk suggested.
TNF inhibitors “work across the board in early disease,” she observed. “The problem is that after a year or two that only 44% of people are left on their first TNF, and why is that?” Reasons for the loss of effect are not known. Using a drug that works in a different way might prove to be the answer, such as seen here with abatacept in seropositive patients with the shared episode, but further studies will be needed to validate the Early AMPLE findings.
Bristol-Myers Squibb sponsored the study. Dr. Bykerk disclosed receiving grant or research support paid to her institution from BMS, as well as Amgen and UCB. She also disclosed acting as a consultant to BMS and multiple other pharmaceutical companies. Several coauthors were employees and shareholders in BMS, or had acted as consultants to BMS.
SOURCE: Rigby W et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):263-4. Abstract LB0008 , doi: 10.1136/annrheumdis-2019-eular.8668.
REPORTING FROM THE EULAR 2019 Congress
Recognize and assess RA fatigue routinely, rheumatology experts urge
MADRID – Fatigue is one of the most frequent features of rheumatoid arthritis, and it needs to be assessed and addressed, several leading rheumatology experts urged at the European Congress of Rheumatology.
“Fatigue is an outcome of outstanding importance for patients with rheumatoid arthritis, and therefore it should be an outcome of outstanding importance for clinicians who take care of these patients,” said José António Pereira da Silva, MD, PhD, a professor of rheumatology at the University of Coimbra (Portugal) during a clinical science session dedicated to the topic.
“Fatigue is described as being significant by as many as 40%-80% of all patients with rheumatoid arthritis, and described as being severe by 41%-49% of these patients according to different studies,” Dr. da Silva said.
“The impact upon the quality of life from the patients’ perspective is quite varied but always rather important, if not ‘dramatic,’ ” Dr. da Silva said. Fatigue needs to be part of treatment targets alongside disease activity and thus regularly measured, he added.
The problem of fatigue
The problem, however, is that fatigue is such a complex construct, observed James Galloway, MBChB, PhD, of the Centre for Rheumatic Diseases at King’s College London. “It’s definitely multifactorial in origin; it’s a combination of inflammatory disease, psychosocial situations, and comorbidity.”
Moreover, said Dr. Galloway, “what people describe as fatigue is multidimensional; it’s not just how well you sleep, but how much energy you have, and it’s also how motivated you are.” The fatigue that accompanies RA is different from the fatigue that is experienced in daily life, he noted, and it has a huge impact on patients’ lives.
Determining the cause of fatigue can be challenging, said Wan-Fai Ng, MBChB, PhD, professor of rheumatology at the Institute of Cellular Medicine at Newcastle (England) University.
“Fatigue is a syndrome that often coexists with other symptoms, and there may be different type of fatigue,” Dr. Ng said. He noted that there were many potential underlying biological mechanisms, but the most studied so far is inflammation. Fatigue is probably driven, at least in part, by “sickness behavior” and there are frequent associations between fatigue and chronic inflammatory conditions such as RA and Sjögren’s syndrome.
“I think the role of conventional inflammatory mechanisms, at least in chronic fatigue in chronic conditions, remains unclear,” Dr. Ng added. “The biological systems, for example the vagus nerve, that regulate the immune system may play key roles in fatigue, especially in chronic inflammatory states.”
Whatever the underlying mechanism, it’s clear that there are multiple factors at play that need addressing if fatigue is to be properly addressed in the clinic. Dr. da Silva unveiled a new path analysis model that will be published in a future issue of Clinical and Experimental Rheumatology that showed how disease activity, pain, disability, sleep disturbance, and depression might all interlink to account for fatigue in patients with RA.
Young or old, fatigue is a prominent, persistent symptom
Fatigue is not just a problem in older adults with rheumatic and musculoskeletal diseases, as Ellen Dalen Arnstad, MD, pointed out in a separate session at the congress. Younger adults and adolescents are also often affected, as demonstrated by data she presented from an 18-year follow-up study of individuals with juvenile idiopathic arthritis (JIA).
An oft-used definition of fatigue, she said was “a persistent, overwhelming sense of tiredness, weakness, and exhaustion.” This results in “decreased capacity of physical function or mental work and is unrelieved by sleep or rests.”
Dr. Arnstad, a pediatric rheumatologist at the Hospital of Levanger in Norway and PhD student at the Norwegian University of Science and Technology in Trondheim, presented data from the Nordic JIA study of 377 subjects who were assessed for fatigue. These showed that there were higher levels of fatigue among participants with active disease, pain, and self-reported health problems. The mean Fatigue Severity Scale score was 3.2 overall, with a higher score in females (3.5) versus males (2.5).
“We found highest mean fatigue scores among those with bad physical and mental health,” Dr. Arnstad reported. Just over a quarter (26%) of patients had severe fatigue, which was defined as a score of 4 or more.
“Fatigue is a prominent symptom in JIA after 18 years of disease duration,” and it “should be measured in a long-term follow-up, both in clinical and research settings,” Dr. Arnstad said.
How should fatigue in RA be assessed?
“Fatigue is recognized by OMERACT [Outcome Measures in Rheumatology Clinical Trials group] as being one of the measured outcome factors in rheumatoid arthritis, one that we should all be taking care of,” Dr. da Silva said. It was added alongside the core set of measures that should be used in all trials “wherever possible.”
So how should fatigue be measured in practice? There are lots of instruments available. Indeed, Dr. da Silva and associates recently counted more than 12, but there is no consensus and no guidelines on which should be used.
“We propose to use a single-item instrument as a screening tool, like the BRAF NRS [Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale] or RAID-F [Rheumatoid Arthritis Impact of Disease–Fatigue domain], which would be supplemented by additional multidimensional assessments if significant levels of fatigue are identified,” he said in an interview. “This will be particularly useful when the aims are to explore causality of fatigue or the efficacy of an intervention.”
Dr. da Silva noted after his presentation that the RAID-F score is routinely used at his practice. “It’s an extremely useful instrument in trying to assess how the patient is dealing with rheumatoid arthritis,” he said. He emphasized that fatigue needed to be considered separately from disease activity and that “it should be part of treatment targets and it should be regularly measured in both research and clinical practice.”
How can fatigue in RA be treated?
When faced with a patient with RA who is experiencing fatigue, it’s important to take a full history and try to determine the cause or contributing factors, Dr. Galloway advised. “I think it’s really important to [take a history of this] specific symptom in the same way you take a history of articular pain.” Consider the onset of fatigue, for example. Is it sudden or linked to a particular stressor or life event, or has its development been more gradual? What’s been the clinical course, duration, and daily pattern? Are there any factors that might alleviate it or exacerbate it? What’s the impact on the patient’s daily life – both in terms of work and social participation?
Treating RA more effectively might help, “but that is unlikely to be sufficient,” Dr. Galloway said, observing that “leaving uncontrolled inflammation is bad, but, in 2019, more inflammation is probably not the solution to fatigue.” Instead, he suggested looking for and treating comorbidities that might be contributing to the fatigue, such as anemia, endocrine or cardiac disease, or perhaps sleep apnea or depression, among others.
“I would discourage the prescribing, for the large part, of drugs for fatigue; that’s because that’s where the evidence is probably the least strong,” Dr. Galloway said. However, there is much better evidence for the use of exercise training in RA and for combining exercise and psychosocial approaches. Improving sleep hygiene may also be beneficial for some patients.
The bottom line is that “fatigue matters” and should be “talked about more with our patients,” Dr. Galloway said.
Dr. da Silva and Dr. Arnstad had no financial conflicts of interest. Dr. Ng disclosed research collaborations with Resolve Therapeutics, electroCore, GlaxoSmithKline, and AbbVie. He also disclosed acting as a consultant for Novartis, GlaxoSmithKline, AbbVie, MedImmune, Pfizer, and Bristol-Myers Squibb. Dr. Galloway disclosed receiving honoraria for speaking at meetings, support for conference travel, or both from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer, and UCB.
SOURCES: da Silva J. Ann Rheum Dis. Jun 2019;78(Suppl 2):15. Abstract SP0052, doi: 10.1136/annrheumdis-2019-eular.8454; Galloway J. Ann Rheum Dis. Jun 2019;78(Suppl 2):15. Abstract SP0053, doi: 10.1136/annrheumdis-2019-eular.8483; Arnstad ED et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):176. Abstract OP201, doi: 10.1136/annrheumdis-2019-eular.4006
MADRID – Fatigue is one of the most frequent features of rheumatoid arthritis, and it needs to be assessed and addressed, several leading rheumatology experts urged at the European Congress of Rheumatology.
“Fatigue is an outcome of outstanding importance for patients with rheumatoid arthritis, and therefore it should be an outcome of outstanding importance for clinicians who take care of these patients,” said José António Pereira da Silva, MD, PhD, a professor of rheumatology at the University of Coimbra (Portugal) during a clinical science session dedicated to the topic.
“Fatigue is described as being significant by as many as 40%-80% of all patients with rheumatoid arthritis, and described as being severe by 41%-49% of these patients according to different studies,” Dr. da Silva said.
“The impact upon the quality of life from the patients’ perspective is quite varied but always rather important, if not ‘dramatic,’ ” Dr. da Silva said. Fatigue needs to be part of treatment targets alongside disease activity and thus regularly measured, he added.
The problem of fatigue
The problem, however, is that fatigue is such a complex construct, observed James Galloway, MBChB, PhD, of the Centre for Rheumatic Diseases at King’s College London. “It’s definitely multifactorial in origin; it’s a combination of inflammatory disease, psychosocial situations, and comorbidity.”
Moreover, said Dr. Galloway, “what people describe as fatigue is multidimensional; it’s not just how well you sleep, but how much energy you have, and it’s also how motivated you are.” The fatigue that accompanies RA is different from the fatigue that is experienced in daily life, he noted, and it has a huge impact on patients’ lives.
Determining the cause of fatigue can be challenging, said Wan-Fai Ng, MBChB, PhD, professor of rheumatology at the Institute of Cellular Medicine at Newcastle (England) University.
“Fatigue is a syndrome that often coexists with other symptoms, and there may be different type of fatigue,” Dr. Ng said. He noted that there were many potential underlying biological mechanisms, but the most studied so far is inflammation. Fatigue is probably driven, at least in part, by “sickness behavior” and there are frequent associations between fatigue and chronic inflammatory conditions such as RA and Sjögren’s syndrome.
“I think the role of conventional inflammatory mechanisms, at least in chronic fatigue in chronic conditions, remains unclear,” Dr. Ng added. “The biological systems, for example the vagus nerve, that regulate the immune system may play key roles in fatigue, especially in chronic inflammatory states.”
Whatever the underlying mechanism, it’s clear that there are multiple factors at play that need addressing if fatigue is to be properly addressed in the clinic. Dr. da Silva unveiled a new path analysis model that will be published in a future issue of Clinical and Experimental Rheumatology that showed how disease activity, pain, disability, sleep disturbance, and depression might all interlink to account for fatigue in patients with RA.
Young or old, fatigue is a prominent, persistent symptom
Fatigue is not just a problem in older adults with rheumatic and musculoskeletal diseases, as Ellen Dalen Arnstad, MD, pointed out in a separate session at the congress. Younger adults and adolescents are also often affected, as demonstrated by data she presented from an 18-year follow-up study of individuals with juvenile idiopathic arthritis (JIA).
An oft-used definition of fatigue, she said was “a persistent, overwhelming sense of tiredness, weakness, and exhaustion.” This results in “decreased capacity of physical function or mental work and is unrelieved by sleep or rests.”
Dr. Arnstad, a pediatric rheumatologist at the Hospital of Levanger in Norway and PhD student at the Norwegian University of Science and Technology in Trondheim, presented data from the Nordic JIA study of 377 subjects who were assessed for fatigue. These showed that there were higher levels of fatigue among participants with active disease, pain, and self-reported health problems. The mean Fatigue Severity Scale score was 3.2 overall, with a higher score in females (3.5) versus males (2.5).
“We found highest mean fatigue scores among those with bad physical and mental health,” Dr. Arnstad reported. Just over a quarter (26%) of patients had severe fatigue, which was defined as a score of 4 or more.
“Fatigue is a prominent symptom in JIA after 18 years of disease duration,” and it “should be measured in a long-term follow-up, both in clinical and research settings,” Dr. Arnstad said.
How should fatigue in RA be assessed?
“Fatigue is recognized by OMERACT [Outcome Measures in Rheumatology Clinical Trials group] as being one of the measured outcome factors in rheumatoid arthritis, one that we should all be taking care of,” Dr. da Silva said. It was added alongside the core set of measures that should be used in all trials “wherever possible.”
So how should fatigue be measured in practice? There are lots of instruments available. Indeed, Dr. da Silva and associates recently counted more than 12, but there is no consensus and no guidelines on which should be used.
“We propose to use a single-item instrument as a screening tool, like the BRAF NRS [Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale] or RAID-F [Rheumatoid Arthritis Impact of Disease–Fatigue domain], which would be supplemented by additional multidimensional assessments if significant levels of fatigue are identified,” he said in an interview. “This will be particularly useful when the aims are to explore causality of fatigue or the efficacy of an intervention.”
Dr. da Silva noted after his presentation that the RAID-F score is routinely used at his practice. “It’s an extremely useful instrument in trying to assess how the patient is dealing with rheumatoid arthritis,” he said. He emphasized that fatigue needed to be considered separately from disease activity and that “it should be part of treatment targets and it should be regularly measured in both research and clinical practice.”
How can fatigue in RA be treated?
When faced with a patient with RA who is experiencing fatigue, it’s important to take a full history and try to determine the cause or contributing factors, Dr. Galloway advised. “I think it’s really important to [take a history of this] specific symptom in the same way you take a history of articular pain.” Consider the onset of fatigue, for example. Is it sudden or linked to a particular stressor or life event, or has its development been more gradual? What’s been the clinical course, duration, and daily pattern? Are there any factors that might alleviate it or exacerbate it? What’s the impact on the patient’s daily life – both in terms of work and social participation?
Treating RA more effectively might help, “but that is unlikely to be sufficient,” Dr. Galloway said, observing that “leaving uncontrolled inflammation is bad, but, in 2019, more inflammation is probably not the solution to fatigue.” Instead, he suggested looking for and treating comorbidities that might be contributing to the fatigue, such as anemia, endocrine or cardiac disease, or perhaps sleep apnea or depression, among others.
“I would discourage the prescribing, for the large part, of drugs for fatigue; that’s because that’s where the evidence is probably the least strong,” Dr. Galloway said. However, there is much better evidence for the use of exercise training in RA and for combining exercise and psychosocial approaches. Improving sleep hygiene may also be beneficial for some patients.
The bottom line is that “fatigue matters” and should be “talked about more with our patients,” Dr. Galloway said.
Dr. da Silva and Dr. Arnstad had no financial conflicts of interest. Dr. Ng disclosed research collaborations with Resolve Therapeutics, electroCore, GlaxoSmithKline, and AbbVie. He also disclosed acting as a consultant for Novartis, GlaxoSmithKline, AbbVie, MedImmune, Pfizer, and Bristol-Myers Squibb. Dr. Galloway disclosed receiving honoraria for speaking at meetings, support for conference travel, or both from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer, and UCB.
SOURCES: da Silva J. Ann Rheum Dis. Jun 2019;78(Suppl 2):15. Abstract SP0052, doi: 10.1136/annrheumdis-2019-eular.8454; Galloway J. Ann Rheum Dis. Jun 2019;78(Suppl 2):15. Abstract SP0053, doi: 10.1136/annrheumdis-2019-eular.8483; Arnstad ED et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):176. Abstract OP201, doi: 10.1136/annrheumdis-2019-eular.4006
MADRID – Fatigue is one of the most frequent features of rheumatoid arthritis, and it needs to be assessed and addressed, several leading rheumatology experts urged at the European Congress of Rheumatology.
“Fatigue is an outcome of outstanding importance for patients with rheumatoid arthritis, and therefore it should be an outcome of outstanding importance for clinicians who take care of these patients,” said José António Pereira da Silva, MD, PhD, a professor of rheumatology at the University of Coimbra (Portugal) during a clinical science session dedicated to the topic.
“Fatigue is described as being significant by as many as 40%-80% of all patients with rheumatoid arthritis, and described as being severe by 41%-49% of these patients according to different studies,” Dr. da Silva said.
“The impact upon the quality of life from the patients’ perspective is quite varied but always rather important, if not ‘dramatic,’ ” Dr. da Silva said. Fatigue needs to be part of treatment targets alongside disease activity and thus regularly measured, he added.
The problem of fatigue
The problem, however, is that fatigue is such a complex construct, observed James Galloway, MBChB, PhD, of the Centre for Rheumatic Diseases at King’s College London. “It’s definitely multifactorial in origin; it’s a combination of inflammatory disease, psychosocial situations, and comorbidity.”
Moreover, said Dr. Galloway, “what people describe as fatigue is multidimensional; it’s not just how well you sleep, but how much energy you have, and it’s also how motivated you are.” The fatigue that accompanies RA is different from the fatigue that is experienced in daily life, he noted, and it has a huge impact on patients’ lives.
Determining the cause of fatigue can be challenging, said Wan-Fai Ng, MBChB, PhD, professor of rheumatology at the Institute of Cellular Medicine at Newcastle (England) University.
“Fatigue is a syndrome that often coexists with other symptoms, and there may be different type of fatigue,” Dr. Ng said. He noted that there were many potential underlying biological mechanisms, but the most studied so far is inflammation. Fatigue is probably driven, at least in part, by “sickness behavior” and there are frequent associations between fatigue and chronic inflammatory conditions such as RA and Sjögren’s syndrome.
“I think the role of conventional inflammatory mechanisms, at least in chronic fatigue in chronic conditions, remains unclear,” Dr. Ng added. “The biological systems, for example the vagus nerve, that regulate the immune system may play key roles in fatigue, especially in chronic inflammatory states.”
Whatever the underlying mechanism, it’s clear that there are multiple factors at play that need addressing if fatigue is to be properly addressed in the clinic. Dr. da Silva unveiled a new path analysis model that will be published in a future issue of Clinical and Experimental Rheumatology that showed how disease activity, pain, disability, sleep disturbance, and depression might all interlink to account for fatigue in patients with RA.
Young or old, fatigue is a prominent, persistent symptom
Fatigue is not just a problem in older adults with rheumatic and musculoskeletal diseases, as Ellen Dalen Arnstad, MD, pointed out in a separate session at the congress. Younger adults and adolescents are also often affected, as demonstrated by data she presented from an 18-year follow-up study of individuals with juvenile idiopathic arthritis (JIA).
An oft-used definition of fatigue, she said was “a persistent, overwhelming sense of tiredness, weakness, and exhaustion.” This results in “decreased capacity of physical function or mental work and is unrelieved by sleep or rests.”
Dr. Arnstad, a pediatric rheumatologist at the Hospital of Levanger in Norway and PhD student at the Norwegian University of Science and Technology in Trondheim, presented data from the Nordic JIA study of 377 subjects who were assessed for fatigue. These showed that there were higher levels of fatigue among participants with active disease, pain, and self-reported health problems. The mean Fatigue Severity Scale score was 3.2 overall, with a higher score in females (3.5) versus males (2.5).
“We found highest mean fatigue scores among those with bad physical and mental health,” Dr. Arnstad reported. Just over a quarter (26%) of patients had severe fatigue, which was defined as a score of 4 or more.
“Fatigue is a prominent symptom in JIA after 18 years of disease duration,” and it “should be measured in a long-term follow-up, both in clinical and research settings,” Dr. Arnstad said.
How should fatigue in RA be assessed?
“Fatigue is recognized by OMERACT [Outcome Measures in Rheumatology Clinical Trials group] as being one of the measured outcome factors in rheumatoid arthritis, one that we should all be taking care of,” Dr. da Silva said. It was added alongside the core set of measures that should be used in all trials “wherever possible.”
So how should fatigue be measured in practice? There are lots of instruments available. Indeed, Dr. da Silva and associates recently counted more than 12, but there is no consensus and no guidelines on which should be used.
“We propose to use a single-item instrument as a screening tool, like the BRAF NRS [Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale] or RAID-F [Rheumatoid Arthritis Impact of Disease–Fatigue domain], which would be supplemented by additional multidimensional assessments if significant levels of fatigue are identified,” he said in an interview. “This will be particularly useful when the aims are to explore causality of fatigue or the efficacy of an intervention.”
Dr. da Silva noted after his presentation that the RAID-F score is routinely used at his practice. “It’s an extremely useful instrument in trying to assess how the patient is dealing with rheumatoid arthritis,” he said. He emphasized that fatigue needed to be considered separately from disease activity and that “it should be part of treatment targets and it should be regularly measured in both research and clinical practice.”
How can fatigue in RA be treated?
When faced with a patient with RA who is experiencing fatigue, it’s important to take a full history and try to determine the cause or contributing factors, Dr. Galloway advised. “I think it’s really important to [take a history of this] specific symptom in the same way you take a history of articular pain.” Consider the onset of fatigue, for example. Is it sudden or linked to a particular stressor or life event, or has its development been more gradual? What’s been the clinical course, duration, and daily pattern? Are there any factors that might alleviate it or exacerbate it? What’s the impact on the patient’s daily life – both in terms of work and social participation?
Treating RA more effectively might help, “but that is unlikely to be sufficient,” Dr. Galloway said, observing that “leaving uncontrolled inflammation is bad, but, in 2019, more inflammation is probably not the solution to fatigue.” Instead, he suggested looking for and treating comorbidities that might be contributing to the fatigue, such as anemia, endocrine or cardiac disease, or perhaps sleep apnea or depression, among others.
“I would discourage the prescribing, for the large part, of drugs for fatigue; that’s because that’s where the evidence is probably the least strong,” Dr. Galloway said. However, there is much better evidence for the use of exercise training in RA and for combining exercise and psychosocial approaches. Improving sleep hygiene may also be beneficial for some patients.
The bottom line is that “fatigue matters” and should be “talked about more with our patients,” Dr. Galloway said.
Dr. da Silva and Dr. Arnstad had no financial conflicts of interest. Dr. Ng disclosed research collaborations with Resolve Therapeutics, electroCore, GlaxoSmithKline, and AbbVie. He also disclosed acting as a consultant for Novartis, GlaxoSmithKline, AbbVie, MedImmune, Pfizer, and Bristol-Myers Squibb. Dr. Galloway disclosed receiving honoraria for speaking at meetings, support for conference travel, or both from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer, and UCB.
SOURCES: da Silva J. Ann Rheum Dis. Jun 2019;78(Suppl 2):15. Abstract SP0052, doi: 10.1136/annrheumdis-2019-eular.8454; Galloway J. Ann Rheum Dis. Jun 2019;78(Suppl 2):15. Abstract SP0053, doi: 10.1136/annrheumdis-2019-eular.8483; Arnstad ED et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):176. Abstract OP201, doi: 10.1136/annrheumdis-2019-eular.4006
REPORTING FROM EULAR 2019 CONGRESS
Mechanism does not matter for second-line biologic choice in JIA
MADRID – When biologic treatment is indicated after initial tumor necrosis factor (TNF) inhibitor therapy for juvenile idiopathic arthritis (JIA) has failed, the mechanism of action of the second biologic does not appear to matter, according to data presented at the European Congress of Rheumatology.
“There appears to be no difference in effectiveness outcomes or drug survival in patients starting a second TNF inhibitor versus an alternative class of biologic,” said Lianne Kearsley-Fleet, an epidemiologist at the Centre for Epidemiology Versus Arthritis at the University of Manchester (England).
Indeed, at 6 months, there were no significant differences among patients who had switched from a TNF inhibitor to another TNF inhibitor or to a biologic with an alternative mechanism of action in terms of:
- The change in Juvenile Arthritis Disease Activity Score (JADAS)-71 from baseline (mean score change, 7.3 with second TNF inhibitor vs. 8.5 with an alternative biologic class).
- The percentage of patients achieving an American College of Rheumatology Pediatric 90% response (22% vs. 15%).
- The proportion of patients achieving minimal disease activity (30% vs. 23%).
- The percentage reaching a minimal clinically important difference (MCID; 44% vs. 43%).
There was also no difference between switching to a TNF inhibitor or alternative biologic in terms of the duration of time patients remained treated with the second-line agent.
“After 1 year, 62% of patients remained on their biologic therapy, and when we looked at drug survival over the course of that year, there was no difference between the two cohorts,” Mrs. Kearsley-Fleet reported. There was no difference also in the reasons for stopping the second biologic.
“We now have a wide range of biologic therapies available; however, there is no evidence regarding which biologic should be prescribed [in JIA], and if patients switch, which order this should be,” Mrs. Kearsley-Fleet stated. Current NHS England guidelines recommend that most patients with JIA should start a TNF inhibitor (unless they are rheumatoid factor positive, in which case they should be treated with rituximab [Rituxan]), and if the first fails, to switch to a second TNF inhibitor rather than to change class. The evidence for this is limited, she noted, adding that adult guidelines for rheumatoid arthritis now recommended a change of class if not contraindicated.
Using data from two pediatric biologics registers – the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN) and Biologics for Children with Rheumatic Diseases (BCRD) – Mrs. Kearsley-Fleet and her associates looked at data on 241 children and adolescents with polyarticular JIA (or oligoarticular-extended JIA) starting a second biologic. The aim was to compare the effectiveness of starting a second TNF inhibitor versus switching to an alternative class of agent, such as a B-cell depleting agent such as rituximab, in routine clinical practice.
A majority (n = 188; 78%) of patients had etanercept (Enbrel) as their starting TNF inhibitor and those switching to a second TNF inhibitor (n = 196) were most likely to be given adalimumab (Humira; 58%). Patients starting a biologic with another mode of action (n = 45) were most likely to be given the interleukin-6 inhibitor tocilizumab (73%), followed by rituximab in 13%, and abatacept (Orencia) in 11%. The main reasons for switching to another biologic – TNF inhibitor or otherwise – were ineffectiveness (60% with a second TNF inhibitor vs. 62% with another biologic drug class) or adverse events or intolerance (19% vs. 13%, respectively).
The strength of these data are that they come from a very large cohort of children and adolescents starting biologics for JIA, with systematic follow-up and robust statistical methods, Mrs. Kearsley-Fleet said. However, she noted that JIA was rare and that only one-fifth of patients would start a biologic, and just 30% of those patients would then switch to a second biologic.
“We don’t see any reason that the guidelines should be changed,” Mrs. Kearsley-Fleet observed. “However, repeat analysis with a larger sample size is required to reinforce whether there is any advantage of switching or not.”
Versus Arthritis (formerly Arthritis Research UK) and The British Society for Rheumatology provided funding support. Mrs. Kearsley-Fleet had no financial conflicts of interest to disclose.
SOURCE: Kearsley-Fleet L et al. Ann Rheum Dis, Jun 2019;8(Suppl 2):74-5. Abstract OP0016. doi: 10.1136/annrheumdis-2019-eular.415.
MADRID – When biologic treatment is indicated after initial tumor necrosis factor (TNF) inhibitor therapy for juvenile idiopathic arthritis (JIA) has failed, the mechanism of action of the second biologic does not appear to matter, according to data presented at the European Congress of Rheumatology.
“There appears to be no difference in effectiveness outcomes or drug survival in patients starting a second TNF inhibitor versus an alternative class of biologic,” said Lianne Kearsley-Fleet, an epidemiologist at the Centre for Epidemiology Versus Arthritis at the University of Manchester (England).
Indeed, at 6 months, there were no significant differences among patients who had switched from a TNF inhibitor to another TNF inhibitor or to a biologic with an alternative mechanism of action in terms of:
- The change in Juvenile Arthritis Disease Activity Score (JADAS)-71 from baseline (mean score change, 7.3 with second TNF inhibitor vs. 8.5 with an alternative biologic class).
- The percentage of patients achieving an American College of Rheumatology Pediatric 90% response (22% vs. 15%).
- The proportion of patients achieving minimal disease activity (30% vs. 23%).
- The percentage reaching a minimal clinically important difference (MCID; 44% vs. 43%).
There was also no difference between switching to a TNF inhibitor or alternative biologic in terms of the duration of time patients remained treated with the second-line agent.
“After 1 year, 62% of patients remained on their biologic therapy, and when we looked at drug survival over the course of that year, there was no difference between the two cohorts,” Mrs. Kearsley-Fleet reported. There was no difference also in the reasons for stopping the second biologic.
“We now have a wide range of biologic therapies available; however, there is no evidence regarding which biologic should be prescribed [in JIA], and if patients switch, which order this should be,” Mrs. Kearsley-Fleet stated. Current NHS England guidelines recommend that most patients with JIA should start a TNF inhibitor (unless they are rheumatoid factor positive, in which case they should be treated with rituximab [Rituxan]), and if the first fails, to switch to a second TNF inhibitor rather than to change class. The evidence for this is limited, she noted, adding that adult guidelines for rheumatoid arthritis now recommended a change of class if not contraindicated.
Using data from two pediatric biologics registers – the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN) and Biologics for Children with Rheumatic Diseases (BCRD) – Mrs. Kearsley-Fleet and her associates looked at data on 241 children and adolescents with polyarticular JIA (or oligoarticular-extended JIA) starting a second biologic. The aim was to compare the effectiveness of starting a second TNF inhibitor versus switching to an alternative class of agent, such as a B-cell depleting agent such as rituximab, in routine clinical practice.
A majority (n = 188; 78%) of patients had etanercept (Enbrel) as their starting TNF inhibitor and those switching to a second TNF inhibitor (n = 196) were most likely to be given adalimumab (Humira; 58%). Patients starting a biologic with another mode of action (n = 45) were most likely to be given the interleukin-6 inhibitor tocilizumab (73%), followed by rituximab in 13%, and abatacept (Orencia) in 11%. The main reasons for switching to another biologic – TNF inhibitor or otherwise – were ineffectiveness (60% with a second TNF inhibitor vs. 62% with another biologic drug class) or adverse events or intolerance (19% vs. 13%, respectively).
The strength of these data are that they come from a very large cohort of children and adolescents starting biologics for JIA, with systematic follow-up and robust statistical methods, Mrs. Kearsley-Fleet said. However, she noted that JIA was rare and that only one-fifth of patients would start a biologic, and just 30% of those patients would then switch to a second biologic.
“We don’t see any reason that the guidelines should be changed,” Mrs. Kearsley-Fleet observed. “However, repeat analysis with a larger sample size is required to reinforce whether there is any advantage of switching or not.”
Versus Arthritis (formerly Arthritis Research UK) and The British Society for Rheumatology provided funding support. Mrs. Kearsley-Fleet had no financial conflicts of interest to disclose.
SOURCE: Kearsley-Fleet L et al. Ann Rheum Dis, Jun 2019;8(Suppl 2):74-5. Abstract OP0016. doi: 10.1136/annrheumdis-2019-eular.415.
MADRID – When biologic treatment is indicated after initial tumor necrosis factor (TNF) inhibitor therapy for juvenile idiopathic arthritis (JIA) has failed, the mechanism of action of the second biologic does not appear to matter, according to data presented at the European Congress of Rheumatology.
“There appears to be no difference in effectiveness outcomes or drug survival in patients starting a second TNF inhibitor versus an alternative class of biologic,” said Lianne Kearsley-Fleet, an epidemiologist at the Centre for Epidemiology Versus Arthritis at the University of Manchester (England).
Indeed, at 6 months, there were no significant differences among patients who had switched from a TNF inhibitor to another TNF inhibitor or to a biologic with an alternative mechanism of action in terms of:
- The change in Juvenile Arthritis Disease Activity Score (JADAS)-71 from baseline (mean score change, 7.3 with second TNF inhibitor vs. 8.5 with an alternative biologic class).
- The percentage of patients achieving an American College of Rheumatology Pediatric 90% response (22% vs. 15%).
- The proportion of patients achieving minimal disease activity (30% vs. 23%).
- The percentage reaching a minimal clinically important difference (MCID; 44% vs. 43%).
There was also no difference between switching to a TNF inhibitor or alternative biologic in terms of the duration of time patients remained treated with the second-line agent.
“After 1 year, 62% of patients remained on their biologic therapy, and when we looked at drug survival over the course of that year, there was no difference between the two cohorts,” Mrs. Kearsley-Fleet reported. There was no difference also in the reasons for stopping the second biologic.
“We now have a wide range of biologic therapies available; however, there is no evidence regarding which biologic should be prescribed [in JIA], and if patients switch, which order this should be,” Mrs. Kearsley-Fleet stated. Current NHS England guidelines recommend that most patients with JIA should start a TNF inhibitor (unless they are rheumatoid factor positive, in which case they should be treated with rituximab [Rituxan]), and if the first fails, to switch to a second TNF inhibitor rather than to change class. The evidence for this is limited, she noted, adding that adult guidelines for rheumatoid arthritis now recommended a change of class if not contraindicated.
Using data from two pediatric biologics registers – the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN) and Biologics for Children with Rheumatic Diseases (BCRD) – Mrs. Kearsley-Fleet and her associates looked at data on 241 children and adolescents with polyarticular JIA (or oligoarticular-extended JIA) starting a second biologic. The aim was to compare the effectiveness of starting a second TNF inhibitor versus switching to an alternative class of agent, such as a B-cell depleting agent such as rituximab, in routine clinical practice.
A majority (n = 188; 78%) of patients had etanercept (Enbrel) as their starting TNF inhibitor and those switching to a second TNF inhibitor (n = 196) were most likely to be given adalimumab (Humira; 58%). Patients starting a biologic with another mode of action (n = 45) were most likely to be given the interleukin-6 inhibitor tocilizumab (73%), followed by rituximab in 13%, and abatacept (Orencia) in 11%. The main reasons for switching to another biologic – TNF inhibitor or otherwise – were ineffectiveness (60% with a second TNF inhibitor vs. 62% with another biologic drug class) or adverse events or intolerance (19% vs. 13%, respectively).
The strength of these data are that they come from a very large cohort of children and adolescents starting biologics for JIA, with systematic follow-up and robust statistical methods, Mrs. Kearsley-Fleet said. However, she noted that JIA was rare and that only one-fifth of patients would start a biologic, and just 30% of those patients would then switch to a second biologic.
“We don’t see any reason that the guidelines should be changed,” Mrs. Kearsley-Fleet observed. “However, repeat analysis with a larger sample size is required to reinforce whether there is any advantage of switching or not.”
Versus Arthritis (formerly Arthritis Research UK) and The British Society for Rheumatology provided funding support. Mrs. Kearsley-Fleet had no financial conflicts of interest to disclose.
SOURCE: Kearsley-Fleet L et al. Ann Rheum Dis, Jun 2019;8(Suppl 2):74-5. Abstract OP0016. doi: 10.1136/annrheumdis-2019-eular.415.
REPORTING FROM EULAR 2019 Congress
Tildrakizumab shows positive effects in active psoriatic arthritis
MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.
“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.
Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.
The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).
In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”
The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.
The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.
The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”
An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.
“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.
Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”
As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.
“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.
In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.
The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.
SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669
MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.
“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.
Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.
The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).
In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”
The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.
The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.
The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”
An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.
“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.
Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”
As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.
“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.
In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.
The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.
SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669
MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.
“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.
Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.
The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).
In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”
The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.
The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.
The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”
An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.
“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.
Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”
As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.
“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.
In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.
The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.
SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669
REPORTING FROM EULAR 2019 CONGRESS
Key clinical point: Tildrakizumab (Ilumya) significantly improved joint and skin manifestations in patients with psoriatic arthritis.
Major finding: At 24 weeks, more than 70% of patients treated with tildrakizumab versus 50% of those given placebo achieved an American College of Rheumatology (ACR) 20 response.
Study details: Randomized, double-blind, placebo-controlled, multiple-dose, phase 2b study to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis.
Disclosures: The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, speaker fees, or all, from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Gilead, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, UCB, and Sun Pharmaceutical Industries.
Source: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669
Repeated ANA testing after negative result of little diagnostic value
MADRID – Repeated antinuclear antibody testing after a negative result has limited use for the diagnosis of ANA-associated rheumatologic conditions, according to data from a multicenter, retrospective analysis that considered a 7-year period.
Considering more than 7,875 repeated ANA tests in 4,887 patients, “the vast majority of results didn’t change,” Ai Li Yeo, MBBS, a PhD candidate, rheumatologist, and infectious disease fellow at Monash University, Melbourne, reported at the European Congress of Rheumatology.
ANA tests were repeated between 2 and as many as 45 times in individual patients, she reported, but the results of 79% of these tests remained unchanged – 45% of tests were persistently negative and 34% persistently positive using a cutoff titer of 1:160.
“Our study showed that there was a very low yield in repeating an ANA test for the diagnosis of ANA-associated rheumatological conditions unless there was evidence of evolving multisystem clinical features,” Dr. Yeo said.
Indeed, the positive predictive value was just 0.01. “So for a hundred patients staring off with a negative ANA results that on repeat testing became positive, the probability is that one patient will have a new ANA-associated rheumatological condition diagnosis,” Dr. Yeo said.
“ANA testing is frequently performed and is part of the classification criteria for autoimmune conditions such as lupus and scleroderma,” she observed. However, the test provides no information on the severity or activity of the disease, and the value of serial monitoring for such conditions is unclear.
“Minimizing unnecessary tests is a global health economic priority,” Dr. Yeo said. She noted that there are multiple initiatives in place to try to open a dialog about using health care resources most effectively, such as ‘Choosing Wisely’ set up by the American Board of Internal Medicine (ABIM) Foundation.
The aim of the present analysis was to calculate the cost of repeated ANA testing and to see if any change in the ANA result was associated with new diagnoses of ANA-associated rheumatological conditions.
The analysis considered more than 36,700 tests that were performed on samples from more than 28,800 patients within the Monash Health tertiary health network between 2011 and 2018. Of these, 22,657 (62%) had given a negative result and 14,058 (38%) had given a positive result.
“Not surprisingly, the age of those who tested positive was significantly higher than those who tested negative,” Dr. Yeo said (52.6 vs. 48.9 years; P less than .001). There was also a higher number of women than men tested, and women more often tested positive.
Around one-fifth of tests performed were repeat tests, of which 511 (6.5%) changed from being negative to positive over a median of 1.71 years.
“A small percentage of people alternated between results,” Dr. Yeo acknowledged, with 9.4% of people going from a positive to a negative result; 10.5% moving from a negative to a positive result, and 1.9% going from positive to negative to positive.
With repeated tests, just five new diagnoses of ANA-associated rheumatologic conditions were made: two cases of systemic lupus erythematosus (SLE), one case of scleroderma, and two cases of undifferentiated connective tissue disease. There was a range of ANA titers and patterns and evolving clinical features of a multisystem disease.
Based on the direct costs of ANA testing in her health care system, not performing repeated tests could yield significant savings, Dr. Yeo said, a 21.4% reduction, in fact, based on this analysis. The cost of an ANA test in Australia ranges from 15 to 46 euros, making the cost of all tests in this analysis 564,745 euros. Taking away the cost of all the single ANA tests performed (443,209 euros) gives a potential cost saving of more than 121,000 euros, she said.
“We now have an opportunity to prevent unnecessary ANA testing, Dr. Yeo said. “Ultimately, our aim is to change behavior at the start of the ordering cycle by educating medical students and doctors about inappropriate test ordering.”
The majority of repeated tests had been ordered by nonrheumatologists (82% of cases), and Dr. Yeo said that rheumatologists ordered repeat tests in 11% of cases. However, there was little information available in this retrospective analysis as to why the tests had been repeated.
The research was picked as one of the six best clinical abstracts at the meeting, out of a total of almost 5,000 submitted abstracts.
Dr. Yeo reported having no conflicts of interest.
SOURCE: Yeo AL et al. Ann Rheum Dis. Jun 2019;78(suppl 2):76-7, Abstract OP0020. doi: 10.1136/annrheumdis-2019-eular.4517.
MADRID – Repeated antinuclear antibody testing after a negative result has limited use for the diagnosis of ANA-associated rheumatologic conditions, according to data from a multicenter, retrospective analysis that considered a 7-year period.
Considering more than 7,875 repeated ANA tests in 4,887 patients, “the vast majority of results didn’t change,” Ai Li Yeo, MBBS, a PhD candidate, rheumatologist, and infectious disease fellow at Monash University, Melbourne, reported at the European Congress of Rheumatology.
ANA tests were repeated between 2 and as many as 45 times in individual patients, she reported, but the results of 79% of these tests remained unchanged – 45% of tests were persistently negative and 34% persistently positive using a cutoff titer of 1:160.
“Our study showed that there was a very low yield in repeating an ANA test for the diagnosis of ANA-associated rheumatological conditions unless there was evidence of evolving multisystem clinical features,” Dr. Yeo said.
Indeed, the positive predictive value was just 0.01. “So for a hundred patients staring off with a negative ANA results that on repeat testing became positive, the probability is that one patient will have a new ANA-associated rheumatological condition diagnosis,” Dr. Yeo said.
“ANA testing is frequently performed and is part of the classification criteria for autoimmune conditions such as lupus and scleroderma,” she observed. However, the test provides no information on the severity or activity of the disease, and the value of serial monitoring for such conditions is unclear.
“Minimizing unnecessary tests is a global health economic priority,” Dr. Yeo said. She noted that there are multiple initiatives in place to try to open a dialog about using health care resources most effectively, such as ‘Choosing Wisely’ set up by the American Board of Internal Medicine (ABIM) Foundation.
The aim of the present analysis was to calculate the cost of repeated ANA testing and to see if any change in the ANA result was associated with new diagnoses of ANA-associated rheumatological conditions.
The analysis considered more than 36,700 tests that were performed on samples from more than 28,800 patients within the Monash Health tertiary health network between 2011 and 2018. Of these, 22,657 (62%) had given a negative result and 14,058 (38%) had given a positive result.
“Not surprisingly, the age of those who tested positive was significantly higher than those who tested negative,” Dr. Yeo said (52.6 vs. 48.9 years; P less than .001). There was also a higher number of women than men tested, and women more often tested positive.
Around one-fifth of tests performed were repeat tests, of which 511 (6.5%) changed from being negative to positive over a median of 1.71 years.
“A small percentage of people alternated between results,” Dr. Yeo acknowledged, with 9.4% of people going from a positive to a negative result; 10.5% moving from a negative to a positive result, and 1.9% going from positive to negative to positive.
With repeated tests, just five new diagnoses of ANA-associated rheumatologic conditions were made: two cases of systemic lupus erythematosus (SLE), one case of scleroderma, and two cases of undifferentiated connective tissue disease. There was a range of ANA titers and patterns and evolving clinical features of a multisystem disease.
Based on the direct costs of ANA testing in her health care system, not performing repeated tests could yield significant savings, Dr. Yeo said, a 21.4% reduction, in fact, based on this analysis. The cost of an ANA test in Australia ranges from 15 to 46 euros, making the cost of all tests in this analysis 564,745 euros. Taking away the cost of all the single ANA tests performed (443,209 euros) gives a potential cost saving of more than 121,000 euros, she said.
“We now have an opportunity to prevent unnecessary ANA testing, Dr. Yeo said. “Ultimately, our aim is to change behavior at the start of the ordering cycle by educating medical students and doctors about inappropriate test ordering.”
The majority of repeated tests had been ordered by nonrheumatologists (82% of cases), and Dr. Yeo said that rheumatologists ordered repeat tests in 11% of cases. However, there was little information available in this retrospective analysis as to why the tests had been repeated.
The research was picked as one of the six best clinical abstracts at the meeting, out of a total of almost 5,000 submitted abstracts.
Dr. Yeo reported having no conflicts of interest.
SOURCE: Yeo AL et al. Ann Rheum Dis. Jun 2019;78(suppl 2):76-7, Abstract OP0020. doi: 10.1136/annrheumdis-2019-eular.4517.
MADRID – Repeated antinuclear antibody testing after a negative result has limited use for the diagnosis of ANA-associated rheumatologic conditions, according to data from a multicenter, retrospective analysis that considered a 7-year period.
Considering more than 7,875 repeated ANA tests in 4,887 patients, “the vast majority of results didn’t change,” Ai Li Yeo, MBBS, a PhD candidate, rheumatologist, and infectious disease fellow at Monash University, Melbourne, reported at the European Congress of Rheumatology.
ANA tests were repeated between 2 and as many as 45 times in individual patients, she reported, but the results of 79% of these tests remained unchanged – 45% of tests were persistently negative and 34% persistently positive using a cutoff titer of 1:160.
“Our study showed that there was a very low yield in repeating an ANA test for the diagnosis of ANA-associated rheumatological conditions unless there was evidence of evolving multisystem clinical features,” Dr. Yeo said.
Indeed, the positive predictive value was just 0.01. “So for a hundred patients staring off with a negative ANA results that on repeat testing became positive, the probability is that one patient will have a new ANA-associated rheumatological condition diagnosis,” Dr. Yeo said.
“ANA testing is frequently performed and is part of the classification criteria for autoimmune conditions such as lupus and scleroderma,” she observed. However, the test provides no information on the severity or activity of the disease, and the value of serial monitoring for such conditions is unclear.
“Minimizing unnecessary tests is a global health economic priority,” Dr. Yeo said. She noted that there are multiple initiatives in place to try to open a dialog about using health care resources most effectively, such as ‘Choosing Wisely’ set up by the American Board of Internal Medicine (ABIM) Foundation.
The aim of the present analysis was to calculate the cost of repeated ANA testing and to see if any change in the ANA result was associated with new diagnoses of ANA-associated rheumatological conditions.
The analysis considered more than 36,700 tests that were performed on samples from more than 28,800 patients within the Monash Health tertiary health network between 2011 and 2018. Of these, 22,657 (62%) had given a negative result and 14,058 (38%) had given a positive result.
“Not surprisingly, the age of those who tested positive was significantly higher than those who tested negative,” Dr. Yeo said (52.6 vs. 48.9 years; P less than .001). There was also a higher number of women than men tested, and women more often tested positive.
Around one-fifth of tests performed were repeat tests, of which 511 (6.5%) changed from being negative to positive over a median of 1.71 years.
“A small percentage of people alternated between results,” Dr. Yeo acknowledged, with 9.4% of people going from a positive to a negative result; 10.5% moving from a negative to a positive result, and 1.9% going from positive to negative to positive.
With repeated tests, just five new diagnoses of ANA-associated rheumatologic conditions were made: two cases of systemic lupus erythematosus (SLE), one case of scleroderma, and two cases of undifferentiated connective tissue disease. There was a range of ANA titers and patterns and evolving clinical features of a multisystem disease.
Based on the direct costs of ANA testing in her health care system, not performing repeated tests could yield significant savings, Dr. Yeo said, a 21.4% reduction, in fact, based on this analysis. The cost of an ANA test in Australia ranges from 15 to 46 euros, making the cost of all tests in this analysis 564,745 euros. Taking away the cost of all the single ANA tests performed (443,209 euros) gives a potential cost saving of more than 121,000 euros, she said.
“We now have an opportunity to prevent unnecessary ANA testing, Dr. Yeo said. “Ultimately, our aim is to change behavior at the start of the ordering cycle by educating medical students and doctors about inappropriate test ordering.”
The majority of repeated tests had been ordered by nonrheumatologists (82% of cases), and Dr. Yeo said that rheumatologists ordered repeat tests in 11% of cases. However, there was little information available in this retrospective analysis as to why the tests had been repeated.
The research was picked as one of the six best clinical abstracts at the meeting, out of a total of almost 5,000 submitted abstracts.
Dr. Yeo reported having no conflicts of interest.
SOURCE: Yeo AL et al. Ann Rheum Dis. Jun 2019;78(suppl 2):76-7, Abstract OP0020. doi: 10.1136/annrheumdis-2019-eular.4517.
REPORTING FROM EULAR 2019 CONGRESS
RNase drug shows promise for Sjögren’s fatigue
MADRID – RSLV-132, a novel drug that eliminates circulating nucleic acids, improved the symptoms of mental fatigue in patients with primary Sjögren’s syndrome (pSS) in a phase 2, double-blind, randomized, placebo-controlled “proof-of-concept” study.
The mental component of fatigue on the Profile of Fatigue (PRO-F) scale improved by 1.53 points among the patients given RSLV-132, while there was a worsening of 0.06 points in the placebo group (P = .046). Scores range from 0 to 7 on the PRO-F.
There were also improvements in some patient-reported outcomes, namely the EULAR pSS Patient Reported Index (ESSPRI) and the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (FACIT-F), and improvement of neuropsychological measures of cognitive function, but none were statistically significant. All of these outcomes, including fatigue, were secondary outcomes of the study.
“Fatigue is a major issue for patients with Sjögren’s syndrome,” Wan-Fai Ng, MBChB, PhD, said in an interview at the European Congress of Rheumatology. Indeed, fatigue can be disabling in the majority of individuals, he added.
Currently, the best way to manage fatigue is to first ask about it, said Dr. Ng, who is professor of rheumatology at the Institute of Cellular Medicine at Newcastle University, Newcastle-upon-Tyne, England. He then checks for any underlying problem that could be better managed – sleep problems or anemia, for example – and optimizes treatment for any underlying disease. “I think many people would at least feel satisfied that people take the symptoms seriously.”
Dr. Ng and his coauthors investigated the effects of RSLV-132, a first-in-class human RNase fused to the human Fc domain of human immunoglobulin (Ig) G1, in the RESOLVE 132-04 study. This novel drug been designed to increase serum RNase activity to digest RNA-associated immune complexes, Dr. Ng and associates observed in their abstract. As a consequence of this, they say, activation of toll-like receptors and the production of interferon (IFN) is affected, as is B-cell proliferation and the production of autoantibodies – all mechanisms that are “key to pSS pathogenesis.”
The IFN pathway has been implicated in fatigue, Dr. Ng observed when he presented the RESOLVE 132-04 study’s findings, which involved 30 patients with pSS who had been treated for 3 months. Inclusion criteria were pSS as defined by the American-European Consensus Group 2002 criteria, anti-Ro antibody positivity, and increased expression of three IFN-regulated genes: HERC5, EPSTI1, and CMPK2. Exclusion criteria were the use of hydroxychloroquine, prednisolone at daily doses above 10 mg, and the use of biologic disease-modifying antirheumatic drugs.
Patients were randomized in a 3:1 ratio to receive either 10 mg/kg of RSLV-132 (n = 20) or placebo (n = 8) at weeks 0, 1, 2, and then every fortnight until week 12. Dr. Ng noted that although 30 patients were randomized, two patients had dropped out in the placebo group before they could be “treated.”
The primary endpoint was the change in the blood cell gene expression or serum protein levels indicative of reduced inflammation. The results indicated reductions in noncoding RNA molecules in patients who received RSLV-132 versus placebo, “consistent with the mode of action of the molecule.” In addition, “the majority of inflammatory markers were reduced,” Dr. Ng said.
Another finding showed a nonsignificant trend for improvement of 0.8 units in the physical component in the RSLV-132 group, compared against 0.06 units with placebo (P = .142).
Patients who received RSLV-132 reduced the time needed to complete the Digital Symbol Substitution Test by 16.4 s, compared with an increase of 2.8 s for placebo (P = .024).
Similar trends were observed for ESSPRI and FACIT-F scores.
These are very early data and clearly a bigger study would be needed before any conclusions could be drawn, Dr. Ng said in an interview. What these data suggest is that “maybe there is some way that we could manage fatigue, and we just need to go and explore that.”
RSLV-132 has also been studied in patients with systemic lupus erythematosus (Lupus. 2017;26:825-34).
The trial was sponsored by Resolve Therapeutics. Dr. Ng was an investigator in the trial and disclosed other research collaborations with electroCore, GlaxoSmithKline, and AbbVie. He also disclosed acting as a consultant for Novartis, GlaxoSmithKline, AbbVie, MedImmune, Pfizer, and Bristol-Myers Squibb.
Source: Fisher B et al. Ann Rheum Dis. 2019 Jun;78(suppl 2):177, Abstract OP0202. doi: 10.1136/annrheumdis-2019-eular.3098.
MADRID – RSLV-132, a novel drug that eliminates circulating nucleic acids, improved the symptoms of mental fatigue in patients with primary Sjögren’s syndrome (pSS) in a phase 2, double-blind, randomized, placebo-controlled “proof-of-concept” study.
The mental component of fatigue on the Profile of Fatigue (PRO-F) scale improved by 1.53 points among the patients given RSLV-132, while there was a worsening of 0.06 points in the placebo group (P = .046). Scores range from 0 to 7 on the PRO-F.
There were also improvements in some patient-reported outcomes, namely the EULAR pSS Patient Reported Index (ESSPRI) and the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (FACIT-F), and improvement of neuropsychological measures of cognitive function, but none were statistically significant. All of these outcomes, including fatigue, were secondary outcomes of the study.
“Fatigue is a major issue for patients with Sjögren’s syndrome,” Wan-Fai Ng, MBChB, PhD, said in an interview at the European Congress of Rheumatology. Indeed, fatigue can be disabling in the majority of individuals, he added.
Currently, the best way to manage fatigue is to first ask about it, said Dr. Ng, who is professor of rheumatology at the Institute of Cellular Medicine at Newcastle University, Newcastle-upon-Tyne, England. He then checks for any underlying problem that could be better managed – sleep problems or anemia, for example – and optimizes treatment for any underlying disease. “I think many people would at least feel satisfied that people take the symptoms seriously.”
Dr. Ng and his coauthors investigated the effects of RSLV-132, a first-in-class human RNase fused to the human Fc domain of human immunoglobulin (Ig) G1, in the RESOLVE 132-04 study. This novel drug been designed to increase serum RNase activity to digest RNA-associated immune complexes, Dr. Ng and associates observed in their abstract. As a consequence of this, they say, activation of toll-like receptors and the production of interferon (IFN) is affected, as is B-cell proliferation and the production of autoantibodies – all mechanisms that are “key to pSS pathogenesis.”
The IFN pathway has been implicated in fatigue, Dr. Ng observed when he presented the RESOLVE 132-04 study’s findings, which involved 30 patients with pSS who had been treated for 3 months. Inclusion criteria were pSS as defined by the American-European Consensus Group 2002 criteria, anti-Ro antibody positivity, and increased expression of three IFN-regulated genes: HERC5, EPSTI1, and CMPK2. Exclusion criteria were the use of hydroxychloroquine, prednisolone at daily doses above 10 mg, and the use of biologic disease-modifying antirheumatic drugs.
Patients were randomized in a 3:1 ratio to receive either 10 mg/kg of RSLV-132 (n = 20) or placebo (n = 8) at weeks 0, 1, 2, and then every fortnight until week 12. Dr. Ng noted that although 30 patients were randomized, two patients had dropped out in the placebo group before they could be “treated.”
The primary endpoint was the change in the blood cell gene expression or serum protein levels indicative of reduced inflammation. The results indicated reductions in noncoding RNA molecules in patients who received RSLV-132 versus placebo, “consistent with the mode of action of the molecule.” In addition, “the majority of inflammatory markers were reduced,” Dr. Ng said.
Another finding showed a nonsignificant trend for improvement of 0.8 units in the physical component in the RSLV-132 group, compared against 0.06 units with placebo (P = .142).
Patients who received RSLV-132 reduced the time needed to complete the Digital Symbol Substitution Test by 16.4 s, compared with an increase of 2.8 s for placebo (P = .024).
Similar trends were observed for ESSPRI and FACIT-F scores.
These are very early data and clearly a bigger study would be needed before any conclusions could be drawn, Dr. Ng said in an interview. What these data suggest is that “maybe there is some way that we could manage fatigue, and we just need to go and explore that.”
RSLV-132 has also been studied in patients with systemic lupus erythematosus (Lupus. 2017;26:825-34).
The trial was sponsored by Resolve Therapeutics. Dr. Ng was an investigator in the trial and disclosed other research collaborations with electroCore, GlaxoSmithKline, and AbbVie. He also disclosed acting as a consultant for Novartis, GlaxoSmithKline, AbbVie, MedImmune, Pfizer, and Bristol-Myers Squibb.
Source: Fisher B et al. Ann Rheum Dis. 2019 Jun;78(suppl 2):177, Abstract OP0202. doi: 10.1136/annrheumdis-2019-eular.3098.
MADRID – RSLV-132, a novel drug that eliminates circulating nucleic acids, improved the symptoms of mental fatigue in patients with primary Sjögren’s syndrome (pSS) in a phase 2, double-blind, randomized, placebo-controlled “proof-of-concept” study.
The mental component of fatigue on the Profile of Fatigue (PRO-F) scale improved by 1.53 points among the patients given RSLV-132, while there was a worsening of 0.06 points in the placebo group (P = .046). Scores range from 0 to 7 on the PRO-F.
There were also improvements in some patient-reported outcomes, namely the EULAR pSS Patient Reported Index (ESSPRI) and the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (FACIT-F), and improvement of neuropsychological measures of cognitive function, but none were statistically significant. All of these outcomes, including fatigue, were secondary outcomes of the study.
“Fatigue is a major issue for patients with Sjögren’s syndrome,” Wan-Fai Ng, MBChB, PhD, said in an interview at the European Congress of Rheumatology. Indeed, fatigue can be disabling in the majority of individuals, he added.
Currently, the best way to manage fatigue is to first ask about it, said Dr. Ng, who is professor of rheumatology at the Institute of Cellular Medicine at Newcastle University, Newcastle-upon-Tyne, England. He then checks for any underlying problem that could be better managed – sleep problems or anemia, for example – and optimizes treatment for any underlying disease. “I think many people would at least feel satisfied that people take the symptoms seriously.”
Dr. Ng and his coauthors investigated the effects of RSLV-132, a first-in-class human RNase fused to the human Fc domain of human immunoglobulin (Ig) G1, in the RESOLVE 132-04 study. This novel drug been designed to increase serum RNase activity to digest RNA-associated immune complexes, Dr. Ng and associates observed in their abstract. As a consequence of this, they say, activation of toll-like receptors and the production of interferon (IFN) is affected, as is B-cell proliferation and the production of autoantibodies – all mechanisms that are “key to pSS pathogenesis.”
The IFN pathway has been implicated in fatigue, Dr. Ng observed when he presented the RESOLVE 132-04 study’s findings, which involved 30 patients with pSS who had been treated for 3 months. Inclusion criteria were pSS as defined by the American-European Consensus Group 2002 criteria, anti-Ro antibody positivity, and increased expression of three IFN-regulated genes: HERC5, EPSTI1, and CMPK2. Exclusion criteria were the use of hydroxychloroquine, prednisolone at daily doses above 10 mg, and the use of biologic disease-modifying antirheumatic drugs.
Patients were randomized in a 3:1 ratio to receive either 10 mg/kg of RSLV-132 (n = 20) or placebo (n = 8) at weeks 0, 1, 2, and then every fortnight until week 12. Dr. Ng noted that although 30 patients were randomized, two patients had dropped out in the placebo group before they could be “treated.”
The primary endpoint was the change in the blood cell gene expression or serum protein levels indicative of reduced inflammation. The results indicated reductions in noncoding RNA molecules in patients who received RSLV-132 versus placebo, “consistent with the mode of action of the molecule.” In addition, “the majority of inflammatory markers were reduced,” Dr. Ng said.
Another finding showed a nonsignificant trend for improvement of 0.8 units in the physical component in the RSLV-132 group, compared against 0.06 units with placebo (P = .142).
Patients who received RSLV-132 reduced the time needed to complete the Digital Symbol Substitution Test by 16.4 s, compared with an increase of 2.8 s for placebo (P = .024).
Similar trends were observed for ESSPRI and FACIT-F scores.
These are very early data and clearly a bigger study would be needed before any conclusions could be drawn, Dr. Ng said in an interview. What these data suggest is that “maybe there is some way that we could manage fatigue, and we just need to go and explore that.”
RSLV-132 has also been studied in patients with systemic lupus erythematosus (Lupus. 2017;26:825-34).
The trial was sponsored by Resolve Therapeutics. Dr. Ng was an investigator in the trial and disclosed other research collaborations with electroCore, GlaxoSmithKline, and AbbVie. He also disclosed acting as a consultant for Novartis, GlaxoSmithKline, AbbVie, MedImmune, Pfizer, and Bristol-Myers Squibb.
Source: Fisher B et al. Ann Rheum Dis. 2019 Jun;78(suppl 2):177, Abstract OP0202. doi: 10.1136/annrheumdis-2019-eular.3098.
REPORTING FROM EULAR 2019 CONGRESS
Quality standards aim to improve worldwide spondyloarthritis care
MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).
The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.
“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.
“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”
A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.
“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.
Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.
The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.
The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.
The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.
Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”
Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”
The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.
“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”
Dr. Kiltz had no relevant conflicts of interest.
SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.
MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).
The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.
“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.
“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”
A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.
“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.
Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.
The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.
The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.
The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.
Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”
Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”
The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.
“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”
Dr. Kiltz had no relevant conflicts of interest.
SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.
MADRID – Referral, treatment, and rapid access to care are three of nine new quality standards developed by a multidisciplinary task force of the Assessment of SpondyloArthritis international Society (ASAS) with the aim of improving the management of adults with axial spondyloarthritis (axSpA).
The other quality standards look at how to improve patient education and self-management and call for annual review, Uta Kiltz, MD, said at the European Congress of Rheumatology.
“Several unmet needs such as delayed diagnosis and restricted access to treatment have been described in patients with axSpA worldwide,” Dr. Kiltz observed in an interview. Results from the ASAS-COMOSPA study (Ann Rheum Dis. 2018;77[3]:405-11), for example, highlighted inequity in the prescription of biologic disease-modifying antirheumatic drugs across the globe.
“The variation in quality of care is noted across rheumatologic diseases,” said Dr. Kiltz, of Ruhr University Bochum and Rheumazentrum Ruhrgebiet in Herne, Germany. “Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care.”
A major goal of ASAS is to improve quality of care and health outcomes in patients with axSpA. To address the many gaps in current care, the society set out to develop quality standards to optimize patients’ access to care and their overall treatment.
“A quality standard consists of a quality statement accompanied by a measure. The measure can be used to assess the quality of care or service provision specified in the treatment,” Dr. Kiltz explained.
Quality standards are very different from recommendations or guidelines, she stressed. While the latter imply evidence-based actions that should be done to optimally diagnose and treat the disease, quality standards identify resources or processes that need to be optimized in high-priority areas for quality improvement.
The nine ASAS quality standards cover key areas for quality improvement relating to the care of adults with axSpA that need improvement worldwide. The statements were carefully phrased following a consensus, and the tools by which they could be measured agreed.
The first three standards concern the time to referral from primary to specialist care and state that people with a suspicion of axSpA are referred to a rheumatologist within 3 working days, assessed by a rheumatologist within 3 weeks after referral, and have their diagnostic work up completed within 2 months.
The next two quality standards concern pharmacologic management: Disease activity of people with axSpA is monitored under the supervision of a rheumatologist with validated composite scores at least twice a year, and in people with axSpA and active disease despite conventional therapy, treatment escalation to biologics is discussed.
Nonpharmacologic treatment is also covered, with the sixth quality standard stating: “People with axial SpA are informed about the benefits of regular exercise.”
Quality standard 7 states: “People with axSpA are offered education on the disease including self-management within 2 months of diagnosis,” Dr. Kiltz said. Rapid access to care is the focus of quality statement 8: “People with axSpA and disease flare or possible drug-related side effects receive advice within 2 working days of contacting the rheumatologist.”
The ninth and last quality standard states that people with axSpA should have a comprehensive annual review by a rheumatologist.
“These are the first quality standards applicable worldwide for the improvement of health care for adult patients with axSpA,” Dr. Kiltz said. “The ASAS quality standards are all measurable and achievable and are intended to minimize variation in quality of care.”
Dr. Kiltz had no relevant conflicts of interest.
SOURCE: Kiltz U. Ann Rheum Dis. Jun 2019;78(Suppl 2):1-2. Abstract SP0004, doi: 10.1136/annrheumdis-2019-eular.8514.
REPORTING FROM EULAR 2019 CONGRESS
Genetic variant could dictate rituximab response in lupus
MADRID – Response to rituximab in patients with systemic lupus erythematosus (SLE) might be dictated by the presence of a genetic variant that encodes the Fc gamma receptors (FcGRs), expressed on natural killer (NK) cells, according to findings from a single-center, longitudinal cohort study.
It is well known that not everyone with SLE will respond well to rituximab, but that some will, first author Md Yuzaiful Md Yusof, MBChB, PhD, explained in an interview at the European Congress of Rheumatology.
Although data from clinical trials with rituximab in this patient setting have been essentially negative, the methodology of those trials has since been disputed, he observed. Indeed, subsequent data (Ann Rheum Dis. 2017;76:1829-36) have suggested that as many as 80% of patients could achieve a response with rituximab, particularly if there is complete B-cell depletion.
Previous researchers (Ann Rheum Dis. 2012;71:875-7) have shown that a polymorphism (158V) in the Fc gamma receptor IIIA (FCGR3A) gene is associated with the response to rituximab-based therapy in patients with rheumatoid arthritis (RA). This gene is important for antibody-dependent cellular-mediated cytotoxicity (ADCC).
The objective of the current study – an observational, prospective, longitudinal cohort study conducted in Leeds (England) – was therefore to see if the FCGR3A-158V polymorphism might influence response in patients with SLE.
“We were trying to find pretreatment biomarkers that could predict response to rituximab in SLE,” Dr. Md Yusof explained.
For the study, 85 patients who were treated with rituximab were assessed. The cohort was predominantly female (96%), with a mean age of 40 years. All of the patients had antinuclear antibodies, with just over half having anti–double-stranded DNA antibodies, and two-thirds having extractable nuclear antigens. One-third had low complement (C3/C4) levels.
Complete B-cell depletion occurred in 63% of patients with the FCGR3A-158V allele, a significantly higher rate than the 40% observed among those with 158 FF genotype (odds ratio, 2.73; P = .041). A significantly higher percentage of patients with the FCGR3A-158V allele also achieved a major BILAG (British Isles Lupus Assessment Group) response when compared against patients with the 158 FF variant (48% vs. 23%), with an odds ratio of 3.06 (P = .033).
Rituximab’s effect on NK cell-mediated B-cell killing may have played a key role in treatment response. Carrying the FCGR3A-158V allele was associated with greater degranulation activity versus the 158 FF variant.
Lastly, patients were more likely to remain on treatment with rituximab over a 10-year period if they had the FCGR3A-158V allele, compared with the 158 FF variant.
“These data suggest one mechanism by which patients with SLE might become resistant to the effects of rituximab, and could be used to guide therapy in the future,” Dr. Md Yusof suggested.
“Once this finding is validated, the clinical implication is that this genetic testing could be done prior to rituximab to identify those who will respond to therapy,” he postulated. “People with SLE who have this genetic variant with high affinity for rituximab are the ones that are better suited for rituximab therapy,” he added, otherwise a different CD20-directed antibody or alternative B-cell blockade therapies should be used.
The U.K. National Institute for Health Research funded the study. Dr. Md Yusof had no conflicts of interest to disclose; some coauthors disclosed ties to Roche, GlaxoSmithKline, and AstraZeneca, among other companies.
SOURCE: Md Yusof MY et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):1069-70. Abstract SAT0009, doi: 10.1136/annrheumdis-2019-eular.6919.
MADRID – Response to rituximab in patients with systemic lupus erythematosus (SLE) might be dictated by the presence of a genetic variant that encodes the Fc gamma receptors (FcGRs), expressed on natural killer (NK) cells, according to findings from a single-center, longitudinal cohort study.
It is well known that not everyone with SLE will respond well to rituximab, but that some will, first author Md Yuzaiful Md Yusof, MBChB, PhD, explained in an interview at the European Congress of Rheumatology.
Although data from clinical trials with rituximab in this patient setting have been essentially negative, the methodology of those trials has since been disputed, he observed. Indeed, subsequent data (Ann Rheum Dis. 2017;76:1829-36) have suggested that as many as 80% of patients could achieve a response with rituximab, particularly if there is complete B-cell depletion.
Previous researchers (Ann Rheum Dis. 2012;71:875-7) have shown that a polymorphism (158V) in the Fc gamma receptor IIIA (FCGR3A) gene is associated with the response to rituximab-based therapy in patients with rheumatoid arthritis (RA). This gene is important for antibody-dependent cellular-mediated cytotoxicity (ADCC).
The objective of the current study – an observational, prospective, longitudinal cohort study conducted in Leeds (England) – was therefore to see if the FCGR3A-158V polymorphism might influence response in patients with SLE.
“We were trying to find pretreatment biomarkers that could predict response to rituximab in SLE,” Dr. Md Yusof explained.
For the study, 85 patients who were treated with rituximab were assessed. The cohort was predominantly female (96%), with a mean age of 40 years. All of the patients had antinuclear antibodies, with just over half having anti–double-stranded DNA antibodies, and two-thirds having extractable nuclear antigens. One-third had low complement (C3/C4) levels.
Complete B-cell depletion occurred in 63% of patients with the FCGR3A-158V allele, a significantly higher rate than the 40% observed among those with 158 FF genotype (odds ratio, 2.73; P = .041). A significantly higher percentage of patients with the FCGR3A-158V allele also achieved a major BILAG (British Isles Lupus Assessment Group) response when compared against patients with the 158 FF variant (48% vs. 23%), with an odds ratio of 3.06 (P = .033).
Rituximab’s effect on NK cell-mediated B-cell killing may have played a key role in treatment response. Carrying the FCGR3A-158V allele was associated with greater degranulation activity versus the 158 FF variant.
Lastly, patients were more likely to remain on treatment with rituximab over a 10-year period if they had the FCGR3A-158V allele, compared with the 158 FF variant.
“These data suggest one mechanism by which patients with SLE might become resistant to the effects of rituximab, and could be used to guide therapy in the future,” Dr. Md Yusof suggested.
“Once this finding is validated, the clinical implication is that this genetic testing could be done prior to rituximab to identify those who will respond to therapy,” he postulated. “People with SLE who have this genetic variant with high affinity for rituximab are the ones that are better suited for rituximab therapy,” he added, otherwise a different CD20-directed antibody or alternative B-cell blockade therapies should be used.
The U.K. National Institute for Health Research funded the study. Dr. Md Yusof had no conflicts of interest to disclose; some coauthors disclosed ties to Roche, GlaxoSmithKline, and AstraZeneca, among other companies.
SOURCE: Md Yusof MY et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):1069-70. Abstract SAT0009, doi: 10.1136/annrheumdis-2019-eular.6919.
MADRID – Response to rituximab in patients with systemic lupus erythematosus (SLE) might be dictated by the presence of a genetic variant that encodes the Fc gamma receptors (FcGRs), expressed on natural killer (NK) cells, according to findings from a single-center, longitudinal cohort study.
It is well known that not everyone with SLE will respond well to rituximab, but that some will, first author Md Yuzaiful Md Yusof, MBChB, PhD, explained in an interview at the European Congress of Rheumatology.
Although data from clinical trials with rituximab in this patient setting have been essentially negative, the methodology of those trials has since been disputed, he observed. Indeed, subsequent data (Ann Rheum Dis. 2017;76:1829-36) have suggested that as many as 80% of patients could achieve a response with rituximab, particularly if there is complete B-cell depletion.
Previous researchers (Ann Rheum Dis. 2012;71:875-7) have shown that a polymorphism (158V) in the Fc gamma receptor IIIA (FCGR3A) gene is associated with the response to rituximab-based therapy in patients with rheumatoid arthritis (RA). This gene is important for antibody-dependent cellular-mediated cytotoxicity (ADCC).
The objective of the current study – an observational, prospective, longitudinal cohort study conducted in Leeds (England) – was therefore to see if the FCGR3A-158V polymorphism might influence response in patients with SLE.
“We were trying to find pretreatment biomarkers that could predict response to rituximab in SLE,” Dr. Md Yusof explained.
For the study, 85 patients who were treated with rituximab were assessed. The cohort was predominantly female (96%), with a mean age of 40 years. All of the patients had antinuclear antibodies, with just over half having anti–double-stranded DNA antibodies, and two-thirds having extractable nuclear antigens. One-third had low complement (C3/C4) levels.
Complete B-cell depletion occurred in 63% of patients with the FCGR3A-158V allele, a significantly higher rate than the 40% observed among those with 158 FF genotype (odds ratio, 2.73; P = .041). A significantly higher percentage of patients with the FCGR3A-158V allele also achieved a major BILAG (British Isles Lupus Assessment Group) response when compared against patients with the 158 FF variant (48% vs. 23%), with an odds ratio of 3.06 (P = .033).
Rituximab’s effect on NK cell-mediated B-cell killing may have played a key role in treatment response. Carrying the FCGR3A-158V allele was associated with greater degranulation activity versus the 158 FF variant.
Lastly, patients were more likely to remain on treatment with rituximab over a 10-year period if they had the FCGR3A-158V allele, compared with the 158 FF variant.
“These data suggest one mechanism by which patients with SLE might become resistant to the effects of rituximab, and could be used to guide therapy in the future,” Dr. Md Yusof suggested.
“Once this finding is validated, the clinical implication is that this genetic testing could be done prior to rituximab to identify those who will respond to therapy,” he postulated. “People with SLE who have this genetic variant with high affinity for rituximab are the ones that are better suited for rituximab therapy,” he added, otherwise a different CD20-directed antibody or alternative B-cell blockade therapies should be used.
The U.K. National Institute for Health Research funded the study. Dr. Md Yusof had no conflicts of interest to disclose; some coauthors disclosed ties to Roche, GlaxoSmithKline, and AstraZeneca, among other companies.
SOURCE: Md Yusof MY et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):1069-70. Abstract SAT0009, doi: 10.1136/annrheumdis-2019-eular.6919.
REPORTING FROM EULAR 2019 CONGRESS
