Sara Freeman

ROME – Strategies that combine conventional synthetic disease-modifying antirheumatic drugs, such as methotrexate, sulfasalazine, or leflunomide, with a tapered glucocorticoid regimen to rapidly induce remission in early rheumatoid arthritis resulted in remission rates of 60% or higher after 1 year in a Belgian study.

“There is ample evidence that combination therapy for early rheumatoid arthritis (COBRA)-like remission-induction are both clinically and cost-effective, but unfortunately this type of therapy is not yet widely used in practice,” said lead study author Patrick Verschueren, a rheumatologist at the University Hospital in Leuven, Belgium, and professor at KU Leuven. The typical arguments that rheumatologists use against the strategy are that the dosages of prednisone used are unnecessarily high and that the combinations of disease-modifying antirheumatic drugs (DMARDs) are not ideal in terms of efficacy and safety, he said.

“We wanted to resolve the discussion about the ideal remission-induction regimen based on combinations of [conventional] synthetic DMARDs and glucocorticoids. We think this could lead to a wider use of COBRA-like strategies in daily practice.”

Dr. Verschueren presented some of the results of the CareRA [Care in early RA] study to support this view at the European Congress of Rheumatology. In this 2-year, prospective, multicenter, randomized, controlled trial, different intensive combination treatment strategies were compared over the course of 52 weeks in patients with previously untreated, early RA (<1 year).

Of 400 patients who were screened for entry into the trial, 379 were finally recruited and stratified into high- and low-risk groups based on the presence of the classic prognostic markers of joint erosions, rheumatoid factor, and anticitrullinated protein antibody status, and disease activity according to 28-joint disease activity score based on C-reactive protein (DAS28-CRP). In total, there were 289 patients classified as being at high risk and 90 patients classified as having low risk.

Dr. Verschueren reported on the 289 patients who were classified as being at high risk. These patients were randomized to one of three treatment strategies:

• COBRA Classic – methotrexate, sulfasalazine, and 60 mg of prednisone tapered weekly, starting at week 7, to 7.5 mg daily.

• COBRA Slim – methotrexate plus 30 mg of prednisone tapered, starting at week 6, to 5 mg daily.

• COBRA Avant-Garde – methotrexate, leflunomide, and 30 mg of prednisone tapered, starting at week 6, to 5 mg daily.

There were 98 patients in each of the first two treatment arms and 93 in the third. Glucocorticoids were tapered in all patients starting at week 28 and stopped at week 34. From week 40 onward, investigators aimed for DMARD monotherapy.

Remission rates, defined as achieving a DAS28-CRP score of less than 3.2, were 64.3%, 60.2%, and 62.8% of patients in the COBRA-Classic, Slim, and Avant-Garde groups, respectively (P = .840). Other efficacy outcomes, which included the percentage of patients achieving a good EULAR (European League Against Rheumatism) response and a clinically meaningful (score of zero) response using the Health Assessment Questionnaire, did not differ between groups. Changes in radiographic progression between the groups – measured using the Sharp van der Heijde (SvH) score – were also minimal. SvH scores were 1.3 ± 2.1, 1.3 ± 2.5, and 1.0 ± 1.4 at baseline, and these changed over 52 weeks by 0.3 ± 0.5, 0.4 ± 1.1, and 0.3 ± 0.6 in the Classic, Slim, and Avant-Garde groups (P = .581).

At the current time, the COBRA Slim regimen, which consists of methotrexate and tapered prednisone, could be regarded as the ideal remission-induction regimen for all early RA patients, regardless of their prognostic profile, Dr. Verschueren suggested. It had similar efficacy, but fewer adverse events, than did the more complex COBRA strategies, which used higher dosages of glucocorticoids and combinations of DMARDs and with clear advantages over the traditional step-up approach, he said.

There were similar percentages of patients in each of the three groups that experienced at least one adverse event, at 67.3% for the COBRA Classic strategy, 66.3% for the COBRA Slim regimen, and 76.3% for the COBRA Avant-Garde approach. “Certain patients might benefit from DMARD combinations plus step-down glucocorticoids if they can tolerate the treatment schedule and comply with it,” Dr. Verschueren proposed.

“We were surprised that the results of COBRA Slim were so good,” he said in an interview, adding that “there are certainly patients who would benefit more from the DMARD combination schemes, but unfortunately we have no biomarkers to identify these, and a ‘light’ version of the remission-induction scheme seems to have a better risk-benefit balance.”

Until better biomarkers are available, he said, “COBRA Slim seems an ideal one-size-fits-all option for initial treatment of all patients with early RA, provided they are tightly followed afterward and a treat-to-target approach is applied.”

Data on the 90 low-risk patients were presented separately in a poster at the meeting. Patients in this arm included 43 patients who were randomized to receive methotrexate following a tight “step-up” glucocorticoid regimen and 47 patients who were randomized to the COBRA Slim schedule. Results showed that high remission rates were achieved with both regimens, but that the remission-induction achieved with the COBRA Slim strategy was associated with more rapid and sustained disease control. The safety of the two regimens was again comparable.

Dr. Verschueren holds the Pfizer Chair for Early Rheumatoid Arthritis Management at the KU Leuven. The study was conducted in partnership with various rheumatology centers in Flanders (Belgium) and benefited from the support of a Flemish governmental grant provided by the IWT (Innovatie door Wetenschapen Technologie).

ROME – Strategies that combine conventional synthetic disease-modifying antirheumatic drugs, such as methotrexate, sulfasalazine, or leflunomide, with a tapered glucocorticoid regimen to rapidly induce remission in early rheumatoid arthritis resulted in remission rates of 60% or higher after 1 year in a Belgian study.

“There is ample evidence that combination therapy for early rheumatoid arthritis (COBRA)-like remission-induction are both clinically and cost-effective, but unfortunately this type of therapy is not yet widely used in practice,” said lead study author Patrick Verschueren, a rheumatologist at the University Hospital in Leuven, Belgium, and professor at KU Leuven. The typical arguments that rheumatologists use against the strategy are that the dosages of prednisone used are unnecessarily high and that the combinations of disease-modifying antirheumatic drugs (DMARDs) are not ideal in terms of efficacy and safety, he said.

“We wanted to resolve the discussion about the ideal remission-induction regimen based on combinations of [conventional] synthetic DMARDs and glucocorticoids. We think this could lead to a wider use of COBRA-like strategies in daily practice.”

Dr. Verschueren presented some of the results of the CareRA [Care in early RA] study to support this view at the European Congress of Rheumatology. In this 2-year, prospective, multicenter, randomized, controlled trial, different intensive combination treatment strategies were compared over the course of 52 weeks in patients with previously untreated, early RA (<1 year).

Of 400 patients who were screened for entry into the trial, 379 were finally recruited and stratified into high- and low-risk groups based on the presence of the classic prognostic markers of joint erosions, rheumatoid factor, and anticitrullinated protein antibody status, and disease activity according to 28-joint disease activity score based on C-reactive protein (DAS28-CRP). In total, there were 289 patients classified as being at high risk and 90 patients classified as having low risk.

Dr. Verschueren reported on the 289 patients who were classified as being at high risk. These patients were randomized to one of three treatment strategies:

• COBRA Classic – methotrexate, sulfasalazine, and 60 mg of prednisone tapered weekly, starting at week 7, to 7.5 mg daily.

• COBRA Slim – methotrexate plus 30 mg of prednisone tapered, starting at week 6, to 5 mg daily.

• COBRA Avant-Garde – methotrexate, leflunomide, and 30 mg of prednisone tapered, starting at week 6, to 5 mg daily.

There were 98 patients in each of the first two treatment arms and 93 in the third. Glucocorticoids were tapered in all patients starting at week 28 and stopped at week 34. From week 40 onward, investigators aimed for DMARD monotherapy.

Remission rates, defined as achieving a DAS28-CRP score of less than 3.2, were 64.3%, 60.2%, and 62.8% of patients in the COBRA-Classic, Slim, and Avant-Garde groups, respectively (P = .840). Other efficacy outcomes, which included the percentage of patients achieving a good EULAR (European League Against Rheumatism) response and a clinically meaningful (score of zero) response using the Health Assessment Questionnaire, did not differ between groups. Changes in radiographic progression between the groups – measured using the Sharp van der Heijde (SvH) score – were also minimal. SvH scores were 1.3 ± 2.1, 1.3 ± 2.5, and 1.0 ± 1.4 at baseline, and these changed over 52 weeks by 0.3 ± 0.5, 0.4 ± 1.1, and 0.3 ± 0.6 in the Classic, Slim, and Avant-Garde groups (P = .581).

At the current time, the COBRA Slim regimen, which consists of methotrexate and tapered prednisone, could be regarded as the ideal remission-induction regimen for all early RA patients, regardless of their prognostic profile, Dr. Verschueren suggested. It had similar efficacy, but fewer adverse events, than did the more complex COBRA strategies, which used higher dosages of glucocorticoids and combinations of DMARDs and with clear advantages over the traditional step-up approach, he said.

There were similar percentages of patients in each of the three groups that experienced at least one adverse event, at 67.3% for the COBRA Classic strategy, 66.3% for the COBRA Slim regimen, and 76.3% for the COBRA Avant-Garde approach. “Certain patients might benefit from DMARD combinations plus step-down glucocorticoids if they can tolerate the treatment schedule and comply with it,” Dr. Verschueren proposed.

“We were surprised that the results of COBRA Slim were so good,” he said in an interview, adding that “there are certainly patients who would benefit more from the DMARD combination schemes, but unfortunately we have no biomarkers to identify these, and a ‘light’ version of the remission-induction scheme seems to have a better risk-benefit balance.”

Until better biomarkers are available, he said, “COBRA Slim seems an ideal one-size-fits-all option for initial treatment of all patients with early RA, provided they are tightly followed afterward and a treat-to-target approach is applied.”

Data on the 90 low-risk patients were presented separately in a poster at the meeting. Patients in this arm included 43 patients who were randomized to receive methotrexate following a tight “step-up” glucocorticoid regimen and 47 patients who were randomized to the COBRA Slim schedule. Results showed that high remission rates were achieved with both regimens, but that the remission-induction achieved with the COBRA Slim strategy was associated with more rapid and sustained disease control. The safety of the two regimens was again comparable.

Dr. Verschueren holds the Pfizer Chair for Early Rheumatoid Arthritis Management at the KU Leuven. The study was conducted in partnership with various rheumatology centers in Flanders (Belgium) and benefited from the support of a Flemish governmental grant provided by the IWT (Innovatie door Wetenschapen Technologie).

ROME – Strategies that combine conventional synthetic disease-modifying antirheumatic drugs, such as methotrexate, sulfasalazine, or leflunomide, with a tapered glucocorticoid regimen to rapidly induce remission in early rheumatoid arthritis resulted in remission rates of 60% or higher after 1 year in a Belgian study.

“There is ample evidence that combination therapy for early rheumatoid arthritis (COBRA)-like remission-induction are both clinically and cost-effective, but unfortunately this type of therapy is not yet widely used in practice,” said lead study author Patrick Verschueren, a rheumatologist at the University Hospital in Leuven, Belgium, and professor at KU Leuven. The typical arguments that rheumatologists use against the strategy are that the dosages of prednisone used are unnecessarily high and that the combinations of disease-modifying antirheumatic drugs (DMARDs) are not ideal in terms of efficacy and safety, he said.

“We wanted to resolve the discussion about the ideal remission-induction regimen based on combinations of [conventional] synthetic DMARDs and glucocorticoids. We think this could lead to a wider use of COBRA-like strategies in daily practice.”

Dr. Verschueren presented some of the results of the CareRA [Care in early RA] study to support this view at the European Congress of Rheumatology. In this 2-year, prospective, multicenter, randomized, controlled trial, different intensive combination treatment strategies were compared over the course of 52 weeks in patients with previously untreated, early RA (<1 year).

Of 400 patients who were screened for entry into the trial, 379 were finally recruited and stratified into high- and low-risk groups based on the presence of the classic prognostic markers of joint erosions, rheumatoid factor, and anticitrullinated protein antibody status, and disease activity according to 28-joint disease activity score based on C-reactive protein (DAS28-CRP). In total, there were 289 patients classified as being at high risk and 90 patients classified as having low risk.

Dr. Verschueren reported on the 289 patients who were classified as being at high risk. These patients were randomized to one of three treatment strategies:

• COBRA Classic – methotrexate, sulfasalazine, and 60 mg of prednisone tapered weekly, starting at week 7, to 7.5 mg daily.

• COBRA Slim – methotrexate plus 30 mg of prednisone tapered, starting at week 6, to 5 mg daily.

• COBRA Avant-Garde – methotrexate, leflunomide, and 30 mg of prednisone tapered, starting at week 6, to 5 mg daily.

There were 98 patients in each of the first two treatment arms and 93 in the third. Glucocorticoids were tapered in all patients starting at week 28 and stopped at week 34. From week 40 onward, investigators aimed for DMARD monotherapy.

Remission rates, defined as achieving a DAS28-CRP score of less than 3.2, were 64.3%, 60.2%, and 62.8% of patients in the COBRA-Classic, Slim, and Avant-Garde groups, respectively (P = .840). Other efficacy outcomes, which included the percentage of patients achieving a good EULAR (European League Against Rheumatism) response and a clinically meaningful (score of zero) response using the Health Assessment Questionnaire, did not differ between groups. Changes in radiographic progression between the groups – measured using the Sharp van der Heijde (SvH) score – were also minimal. SvH scores were 1.3 ± 2.1, 1.3 ± 2.5, and 1.0 ± 1.4 at baseline, and these changed over 52 weeks by 0.3 ± 0.5, 0.4 ± 1.1, and 0.3 ± 0.6 in the Classic, Slim, and Avant-Garde groups (P = .581).

At the current time, the COBRA Slim regimen, which consists of methotrexate and tapered prednisone, could be regarded as the ideal remission-induction regimen for all early RA patients, regardless of their prognostic profile, Dr. Verschueren suggested. It had similar efficacy, but fewer adverse events, than did the more complex COBRA strategies, which used higher dosages of glucocorticoids and combinations of DMARDs and with clear advantages over the traditional step-up approach, he said.

There were similar percentages of patients in each of the three groups that experienced at least one adverse event, at 67.3% for the COBRA Classic strategy, 66.3% for the COBRA Slim regimen, and 76.3% for the COBRA Avant-Garde approach. “Certain patients might benefit from DMARD combinations plus step-down glucocorticoids if they can tolerate the treatment schedule and comply with it,” Dr. Verschueren proposed.

“We were surprised that the results of COBRA Slim were so good,” he said in an interview, adding that “there are certainly patients who would benefit more from the DMARD combination schemes, but unfortunately we have no biomarkers to identify these, and a ‘light’ version of the remission-induction scheme seems to have a better risk-benefit balance.”

Until better biomarkers are available, he said, “COBRA Slim seems an ideal one-size-fits-all option for initial treatment of all patients with early RA, provided they are tightly followed afterward and a treat-to-target approach is applied.”

Data on the 90 low-risk patients were presented separately in a poster at the meeting. Patients in this arm included 43 patients who were randomized to receive methotrexate following a tight “step-up” glucocorticoid regimen and 47 patients who were randomized to the COBRA Slim schedule. Results showed that high remission rates were achieved with both regimens, but that the remission-induction achieved with the COBRA Slim strategy was associated with more rapid and sustained disease control. The safety of the two regimens was again comparable.

Dr. Verschueren holds the Pfizer Chair for Early Rheumatoid Arthritis Management at the KU Leuven. The study was conducted in partnership with various rheumatology centers in Flanders (Belgium) and benefited from the support of a Flemish governmental grant provided by the IWT (Innovatie door Wetenschapen Technologie).

ROME – Knee joint distraction – a method of relieving mechanical stress on the joint by temporarily pinning it – could help some patients with osteoarthritis avoid the need for a knee prosthesis, judging from preliminary findings from a randomized, controlled, comparative trial.

At 1-year follow-up, all subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Total KOOS score were significantly and progressively improved from baseline in patients who underwent knee distraction (P < .001). Overall the mean change in the Total KOOS score was not significantly different from that in the group of patients who underwent total knee replacement (TKR); although the KOOS subscale of quality of life did show greater improvement with the prosthesis than with distraction (P = .027), it was felt that this will “level out” when data on all 60 patients included in the trial are available. This research, performed at the UMC [University Medical Center] Utrecht and Sint Maartenskliniek in Woerden in the Netherlands, highlights how knee distraction may offer a valuable alternative to TKR, particularly in younger patients with OA, according to Simon Mastbergen, Ph.D., who studies tissue degeneration and regeneration in the department of rheumatology and clinical immunology at UMC Utrecht, and associates (Ann. Rheum. Dis. 2015;74:359-60).

“When you have a total knee prosthesis at a relatively young age, the outcome is not as successful as most people think,” Dr. Mastbergen said in an interview during a poster session at the European Congress of Rheumatology. Around 40% of TKRs are performed in people under the age of 65 years, he observed, and younger patients have a higher risk of revision failure because of mechanical failure as they tend to be more active than elderly patients with knee OA. Indeed, it’s been estimated that around 44% of younger patients who have TKR will need revision surgery at some point, and as secondary procedures are more difficult to perform and can be much more disabling “we need a joint-saving treatment.” Joint distraction is a surgical procedure that aims to gradually separate the two bony ends of a joint for a certain length of time. The method used by the Dutch team involved patients wearing an external frame bridging the knee that consisted of two long tubes with coiled springs inside with pins coming out that are inserted into the opposing soft tissue and bones and moved by about 5 mm each time. Patients wear the frame for 6-8 weeks and are encouraged to try to bear weight on the affected knee, with the aid of crutches if needed. The idea behind the method is that it will allow the joint to repair itself, and the team has already shown that cartilaginous tissue repair does indeed seem to occur (Cartilage 2013;21:1660-7).

Dr. Mastbergen noted that patients who underwent knee joint distraction in the study directly comparing it to TKR exhibited significant widening in the joint space, which is good because it indicates that cartilage has been regained. “We feel that knee joint distraction is an alternative for those [patients] who are ready for total knee prosthesis but are actually too young for [it],” he said.

Sara Freeman/Frontline Medical News

Other randomized controlled trial data from the team was presented during an oral abstract session at the meeting (Ann. Rheum. Dis. 2015;74:108) and showed that knee joint distraction is also as good as high tibial osteotomy, which is another method aimed at relieving mechanical stress on the knee joint. The senior author of the team Floris Lafeber, Ph.D., who presented data on behalf of colleague Dr. Jan Ton van der Woude, noted that there were several similarities between the two procedures in that they were both joint saving and could potentially postpone TKR and had been shown to improve bone turnover and cartilaginous tissue repair.

To compare the two methods, the researchers studied almost 70 patients aged 65 years or younger with medial compartment knee OA who were indicated for high tibial osteotomy. Patients were randomized 2:1 to the two procedures, with 45 undergoing osteotomy and 22 knee joint distraction. Significant improvements in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog pain, and quality of life (EQ-5D) scores were seen in both groups when compared with the preoperative values (P < .05). None of the parameters showed any statistically significant difference between the two procedures at 1-year follow-up. The data led to the conclusion that knee joint distraction had a clinical benefit that was comparable to osteotomy.

However, both the minimum and mean joint space width showed a steeper increase in patients randomized to the knee joint distraction group, suggesting that cartilaginous tissue repair might be better with the latter method.

Sara Freeman/Frontline Medical News

The potential clinical benefit of knee joint distraction was further highlighted in another poster from the team, presented by Dr. Natalia Kuchuk, which showed the effects of the procedure were maintained at 5-year follow-up. Importantly, 80% of the 20 patients studied in this open study still had their own knee joint. The mean age of patients at the time of distraction was 48.5 years. “In young patients, knee joint distraction effectively postpones total knee arthroplasty and is the only treatment which allows regeneration of cartilage,” she said in an interview.

Dr. Lafeber also commented in an interview on the practicalities of the procedure, which is still in its experimental phases. “It’s a rather an invasive procedure but if you compare it to a total knee replacement or high tibial osteotomy it’s less invasive,” he said.

“The surgical procedure takes about half an hour, we place a few pins through soft tissue and bone and the distraction tubes are placed mediolaterally to these pins, so in fact it’s less invasive than many of the other surgical techniques.” The distraction itself is not painful, he added, and actually alleviates OA pain but patients may need painkillers and perhaps antibiotics for short periods during the method.Next steps for the team are to follow up patients in the randomized trials for a longer period of time and refine the distraction device. “This is an off-the-shelf, ‘proof-of-concept’ device, and we are now developing a more patient-friendly, smaller, lighter frame device which is also easier to place by orthopedic surgeons,” Dr. Lafeber said. “Then we will do a comparison with the proof-of-concept device.”

Reumafonds (the Dutch Arthritis Foundation), ZonMw (The Netherlands Organization for Health Research and Development), UMC Utrecht, and Sint Maartinskliniek funded the research. Dr. Mastbergen, Dr. Lafeber, and Dr. Kuchuk had no disclosures to report.

ROME – Knee joint distraction – a method of relieving mechanical stress on the joint by temporarily pinning it – could help some patients with osteoarthritis avoid the need for a knee prosthesis, judging from preliminary findings from a randomized, controlled, comparative trial.

At 1-year follow-up, all subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Total KOOS score were significantly and progressively improved from baseline in patients who underwent knee distraction (P < .001). Overall the mean change in the Total KOOS score was not significantly different from that in the group of patients who underwent total knee replacement (TKR); although the KOOS subscale of quality of life did show greater improvement with the prosthesis than with distraction (P = .027), it was felt that this will “level out” when data on all 60 patients included in the trial are available. This research, performed at the UMC [University Medical Center] Utrecht and Sint Maartenskliniek in Woerden in the Netherlands, highlights how knee distraction may offer a valuable alternative to TKR, particularly in younger patients with OA, according to Simon Mastbergen, Ph.D., who studies tissue degeneration and regeneration in the department of rheumatology and clinical immunology at UMC Utrecht, and associates (Ann. Rheum. Dis. 2015;74:359-60).

“When you have a total knee prosthesis at a relatively young age, the outcome is not as successful as most people think,” Dr. Mastbergen said in an interview during a poster session at the European Congress of Rheumatology. Around 40% of TKRs are performed in people under the age of 65 years, he observed, and younger patients have a higher risk of revision failure because of mechanical failure as they tend to be more active than elderly patients with knee OA. Indeed, it’s been estimated that around 44% of younger patients who have TKR will need revision surgery at some point, and as secondary procedures are more difficult to perform and can be much more disabling “we need a joint-saving treatment.” Joint distraction is a surgical procedure that aims to gradually separate the two bony ends of a joint for a certain length of time. The method used by the Dutch team involved patients wearing an external frame bridging the knee that consisted of two long tubes with coiled springs inside with pins coming out that are inserted into the opposing soft tissue and bones and moved by about 5 mm each time. Patients wear the frame for 6-8 weeks and are encouraged to try to bear weight on the affected knee, with the aid of crutches if needed. The idea behind the method is that it will allow the joint to repair itself, and the team has already shown that cartilaginous tissue repair does indeed seem to occur (Cartilage 2013;21:1660-7).

Dr. Mastbergen noted that patients who underwent knee joint distraction in the study directly comparing it to TKR exhibited significant widening in the joint space, which is good because it indicates that cartilage has been regained. “We feel that knee joint distraction is an alternative for those [patients] who are ready for total knee prosthesis but are actually too young for [it],” he said.

Sara Freeman/Frontline Medical News

Other randomized controlled trial data from the team was presented during an oral abstract session at the meeting (Ann. Rheum. Dis. 2015;74:108) and showed that knee joint distraction is also as good as high tibial osteotomy, which is another method aimed at relieving mechanical stress on the knee joint. The senior author of the team Floris Lafeber, Ph.D., who presented data on behalf of colleague Dr. Jan Ton van der Woude, noted that there were several similarities between the two procedures in that they were both joint saving and could potentially postpone TKR and had been shown to improve bone turnover and cartilaginous tissue repair.

To compare the two methods, the researchers studied almost 70 patients aged 65 years or younger with medial compartment knee OA who were indicated for high tibial osteotomy. Patients were randomized 2:1 to the two procedures, with 45 undergoing osteotomy and 22 knee joint distraction. Significant improvements in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog pain, and quality of life (EQ-5D) scores were seen in both groups when compared with the preoperative values (P < .05). None of the parameters showed any statistically significant difference between the two procedures at 1-year follow-up. The data led to the conclusion that knee joint distraction had a clinical benefit that was comparable to osteotomy.

However, both the minimum and mean joint space width showed a steeper increase in patients randomized to the knee joint distraction group, suggesting that cartilaginous tissue repair might be better with the latter method.

Sara Freeman/Frontline Medical News

The potential clinical benefit of knee joint distraction was further highlighted in another poster from the team, presented by Dr. Natalia Kuchuk, which showed the effects of the procedure were maintained at 5-year follow-up. Importantly, 80% of the 20 patients studied in this open study still had their own knee joint. The mean age of patients at the time of distraction was 48.5 years. “In young patients, knee joint distraction effectively postpones total knee arthroplasty and is the only treatment which allows regeneration of cartilage,” she said in an interview.

Dr. Lafeber also commented in an interview on the practicalities of the procedure, which is still in its experimental phases. “It’s a rather an invasive procedure but if you compare it to a total knee replacement or high tibial osteotomy it’s less invasive,” he said.

“The surgical procedure takes about half an hour, we place a few pins through soft tissue and bone and the distraction tubes are placed mediolaterally to these pins, so in fact it’s less invasive than many of the other surgical techniques.” The distraction itself is not painful, he added, and actually alleviates OA pain but patients may need painkillers and perhaps antibiotics for short periods during the method.Next steps for the team are to follow up patients in the randomized trials for a longer period of time and refine the distraction device. “This is an off-the-shelf, ‘proof-of-concept’ device, and we are now developing a more patient-friendly, smaller, lighter frame device which is also easier to place by orthopedic surgeons,” Dr. Lafeber said. “Then we will do a comparison with the proof-of-concept device.”

Reumafonds (the Dutch Arthritis Foundation), ZonMw (The Netherlands Organization for Health Research and Development), UMC Utrecht, and Sint Maartinskliniek funded the research. Dr. Mastbergen, Dr. Lafeber, and Dr. Kuchuk had no disclosures to report.

ROME – Knee joint distraction – a method of relieving mechanical stress on the joint by temporarily pinning it – could help some patients with osteoarthritis avoid the need for a knee prosthesis, judging from preliminary findings from a randomized, controlled, comparative trial.

At 1-year follow-up, all subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Total KOOS score were significantly and progressively improved from baseline in patients who underwent knee distraction (P < .001). Overall the mean change in the Total KOOS score was not significantly different from that in the group of patients who underwent total knee replacement (TKR); although the KOOS subscale of quality of life did show greater improvement with the prosthesis than with distraction (P = .027), it was felt that this will “level out” when data on all 60 patients included in the trial are available. This research, performed at the UMC [University Medical Center] Utrecht and Sint Maartenskliniek in Woerden in the Netherlands, highlights how knee distraction may offer a valuable alternative to TKR, particularly in younger patients with OA, according to Simon Mastbergen, Ph.D., who studies tissue degeneration and regeneration in the department of rheumatology and clinical immunology at UMC Utrecht, and associates (Ann. Rheum. Dis. 2015;74:359-60).

“When you have a total knee prosthesis at a relatively young age, the outcome is not as successful as most people think,” Dr. Mastbergen said in an interview during a poster session at the European Congress of Rheumatology. Around 40% of TKRs are performed in people under the age of 65 years, he observed, and younger patients have a higher risk of revision failure because of mechanical failure as they tend to be more active than elderly patients with knee OA. Indeed, it’s been estimated that around 44% of younger patients who have TKR will need revision surgery at some point, and as secondary procedures are more difficult to perform and can be much more disabling “we need a joint-saving treatment.” Joint distraction is a surgical procedure that aims to gradually separate the two bony ends of a joint for a certain length of time. The method used by the Dutch team involved patients wearing an external frame bridging the knee that consisted of two long tubes with coiled springs inside with pins coming out that are inserted into the opposing soft tissue and bones and moved by about 5 mm each time. Patients wear the frame for 6-8 weeks and are encouraged to try to bear weight on the affected knee, with the aid of crutches if needed. The idea behind the method is that it will allow the joint to repair itself, and the team has already shown that cartilaginous tissue repair does indeed seem to occur (Cartilage 2013;21:1660-7).

Dr. Mastbergen noted that patients who underwent knee joint distraction in the study directly comparing it to TKR exhibited significant widening in the joint space, which is good because it indicates that cartilage has been regained. “We feel that knee joint distraction is an alternative for those [patients] who are ready for total knee prosthesis but are actually too young for [it],” he said.

Sara Freeman/Frontline Medical News

Other randomized controlled trial data from the team was presented during an oral abstract session at the meeting (Ann. Rheum. Dis. 2015;74:108) and showed that knee joint distraction is also as good as high tibial osteotomy, which is another method aimed at relieving mechanical stress on the knee joint. The senior author of the team Floris Lafeber, Ph.D., who presented data on behalf of colleague Dr. Jan Ton van der Woude, noted that there were several similarities between the two procedures in that they were both joint saving and could potentially postpone TKR and had been shown to improve bone turnover and cartilaginous tissue repair.

To compare the two methods, the researchers studied almost 70 patients aged 65 years or younger with medial compartment knee OA who were indicated for high tibial osteotomy. Patients were randomized 2:1 to the two procedures, with 45 undergoing osteotomy and 22 knee joint distraction. Significant improvements in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog pain, and quality of life (EQ-5D) scores were seen in both groups when compared with the preoperative values (P < .05). None of the parameters showed any statistically significant difference between the two procedures at 1-year follow-up. The data led to the conclusion that knee joint distraction had a clinical benefit that was comparable to osteotomy.

However, both the minimum and mean joint space width showed a steeper increase in patients randomized to the knee joint distraction group, suggesting that cartilaginous tissue repair might be better with the latter method.

Sara Freeman/Frontline Medical News

The potential clinical benefit of knee joint distraction was further highlighted in another poster from the team, presented by Dr. Natalia Kuchuk, which showed the effects of the procedure were maintained at 5-year follow-up. Importantly, 80% of the 20 patients studied in this open study still had their own knee joint. The mean age of patients at the time of distraction was 48.5 years. “In young patients, knee joint distraction effectively postpones total knee arthroplasty and is the only treatment which allows regeneration of cartilage,” she said in an interview.

Dr. Lafeber also commented in an interview on the practicalities of the procedure, which is still in its experimental phases. “It’s a rather an invasive procedure but if you compare it to a total knee replacement or high tibial osteotomy it’s less invasive,” he said.

“The surgical procedure takes about half an hour, we place a few pins through soft tissue and bone and the distraction tubes are placed mediolaterally to these pins, so in fact it’s less invasive than many of the other surgical techniques.” The distraction itself is not painful, he added, and actually alleviates OA pain but patients may need painkillers and perhaps antibiotics for short periods during the method.Next steps for the team are to follow up patients in the randomized trials for a longer period of time and refine the distraction device. “This is an off-the-shelf, ‘proof-of-concept’ device, and we are now developing a more patient-friendly, smaller, lighter frame device which is also easier to place by orthopedic surgeons,” Dr. Lafeber said. “Then we will do a comparison with the proof-of-concept device.”

Reumafonds (the Dutch Arthritis Foundation), ZonMw (The Netherlands Organization for Health Research and Development), UMC Utrecht, and Sint Maartinskliniek funded the research. Dr. Mastbergen, Dr. Lafeber, and Dr. Kuchuk had no disclosures to report.

ROME – New therapies introduced over the past 15 years have vastly improved the lives of patients with rheumatic diseases but are also creating complex treatment scenarios as more female patients consider starting a family or become pregnant while taking medication. At the European Congress of Rheumatology, experts discussed the importance of contraceptive counseling, pregnancy planning, and how to treat pregnant women with rheumatic diseases.

“Nowadays we have such better treatments for our patients that sexuality and contraception is becoming more and more important,” said Dr. Eliza Chakravarty of the Oklahoma Medical Research Foundation in Oklahoma City. Yet contraception is “quite underused in our patients,” she observed.

©Jupiterimages/thinkstockphotos.com

Indeed, in one study looking at the risk of unintended pregnancy in women with lupus, over half (55%) of the 212 women surveyed admitted that they had unprotected sex at least once, with almost a quarter (23%) saying that this was usually in the preceding 3 months (Arthritis Care Res. 2008;59:863-6).

This underuse of contraception is not unique to lupus patients, and there are many reasons why women with rheumatic diseases who are sexually active may not always use adequate contraception. One of these reasons was the lack of time during consultations, which tend to focus on disease management rather than issues such as contraceptive counseling. Other reasons may be misconceptions on fertility or a lack of understanding of the teratogenicity of medications or the effect that hormones may have on disease activity. Women also may be reluctant to take additional medicines or feel uncomfortable discussing the topic with their rheumatologists.

“Patients see their rheumatologist more frequently than any other [health care] provider,” Dr. Chakravarty said, adding that continual follow-up appointments over time provide an opportunity to discuss fertility and changing contraception needs. “Contraception is a component of effective disease management for young women,” she said.

There are many contraceptive methods available, each with pros and cons and varying efficacy, so women have multiple options to choose from to suit their personal preferences and lifestyles. Dr. Chakravarty suggested that, of all the available methods, long-acting reversible contraceptive methods, such as the subdermal implant or intrauterine device, were perhaps the best choice for many women with rheumatic diseases since they are associated with a low rate of accidental pregnancy and after insertion there is little or nothing to do or remember until the devices needed replacing after 3-10 years.

Dr. Monika Østensen of the Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases at St. Olavs Hospital-Trondheim University Hospital, echoed the need for repeated family-planning advice. Of course, pregnancies occur even with the best planning, she said, and the question then is how to manage the rheumatic disease.

The need for treatment will depending on the type of disease, she said, noting that the need generally decreased during pregnancy in women with rheumatoid arthritis (RA) but increased in those with ankylosing spondylitis, most notably in the first and second trimesters (Ann. Rheum. Dis. 2004;63:1212-7). The ideal situation would be to adjust disease-directed therapy if needed before conception, although methotrexate is the only drug with proven teratogenicity that is used for RA and ankylosing spondylitis and that should definitely be stopped, she said.

There is a lot of evidence that methotrexate needs to be stopped before pregnancy. One recent prospective study (Arthritis Rheumatol. 2014;66:1101-10) looked at pregnancy outcomes and methotrexate use and found a high rate of spontaneous abortions if it was used within 10 weeks of conception (14.4%) or in the first trimester (42.5%). The rate of major birth defects was 6.6% if methotrexate was used in early pregnancy, versus 2.9% for women without rheumatic disease or 3.5% in women with rheumatic disease who were not taking the disease-modifying antirheumatic drug (DMARD).

Dr. Østensen advised that, when stopping methotrexate, women should be counseled to wait for one menstrual cycle before attempting to conceive and not to stop therapy without perhaps checking for fertility or switching to another pregnancy-compatible drug. She also stressed that patients who want to become pregnant or who do become pregnant should not immediately stop taking their medication without consulting a rheumatologist. Such an action could result in disease flares, and the aim of therapy should always be to keep the patient in remission or low disease activity and continue drugs that support remission while trying to minimize any likely effects on the fetus.

Leflunomide (Arava), rituximab (Rituxan), abatacept (Orencia), and newer biologics such as tocilizumab (Actemra), ustekinumab (Stelara), and tofacitinb (Xeljanz) are contraindicated because of lack of data on whether they are safe for the fetus. If a woman did become pregnant while taking any of these drugs or even methotrexate, then taking a careful history and performing fetal ultrasound and amniocentesis may be the best approach to determine what action to take and if pregnancy termination should be considered.

Tumor necrosis factor-alpha inhibitors (TNFi), the best-studied biologic DMARDs, can be given before conception and during the first and early second trimester; however, use in late pregnancy requires different considerations because transplacental passage varies based on differences related to their structure. Some TNFis, such as certolizumab pegol (Cimzia), have small affinity to the fetal Fc receptor or no Fc part and show low transplacental passage to the fetus. TNFis that possess an Fc part of immunoglobulin G1, however, allow high amounts of transfer and should be avoided in the third trimester whenever possible, Dr. Østensen said.

Data are sparse on human pregnancy exposure and fetal side effects and outcomes for most other biologics, so decisions to use biologics targeting B-cells, T-cell activation, or cytokines like interleukin (IL)-6, IL-23, IL-17, or IL-1beta must be based on the severity of maternal disease and reserved for cases in which no other safe options are available, Dr. Østensen cautioned.

So how can acute arthritis be treated during pregnancy? Options in RA include NSAIDs, short-term oral prednisone with rapid tapering or intramuscular injection of triamcinolone. Intra-articular steroid injection also might be considered, and TNFi in patients with severe polyarthritis. Spondyloarthritis might be treated with NSAIDs, intramuscular triamcinolone, or intra-articular steroid injection, with TNFi in severe cases.

Newer approaches to managing arthritis during pregnancy are to perhaps prescribe a TNFi with a low propensity for transplacental passage or to use a flexible regimen of TNFi by reducing the dose or prolonging the interval between administrations.

Continuing medications such as hydroxychloroquine, sulfasalazine, or azathioprine might be in some patients’ best interests to support remission and keep disease activity low, Dr. Østensen suggested. She noted that prednisone should be used at a low (5-7.5 mg) dose during pregnancy and that the aim should be to try to slowly reduce the use of pregnancy-compatible medications that are not necessary for continued remission, keeping a close eye on patients’ disease activity to ensure that no flares occur.

Dr. Chakravarty had no financial disclosures. Dr. Østensen reported receiving speaker fees and honoraria from UCB, Roche, AbbVie, MSD, Pfizer, and New Bridge.

ROME – New therapies introduced over the past 15 years have vastly improved the lives of patients with rheumatic diseases but are also creating complex treatment scenarios as more female patients consider starting a family or become pregnant while taking medication. At the European Congress of Rheumatology, experts discussed the importance of contraceptive counseling, pregnancy planning, and how to treat pregnant women with rheumatic diseases.

“Nowadays we have such better treatments for our patients that sexuality and contraception is becoming more and more important,” said Dr. Eliza Chakravarty of the Oklahoma Medical Research Foundation in Oklahoma City. Yet contraception is “quite underused in our patients,” she observed.

©Jupiterimages/thinkstockphotos.com

Indeed, in one study looking at the risk of unintended pregnancy in women with lupus, over half (55%) of the 212 women surveyed admitted that they had unprotected sex at least once, with almost a quarter (23%) saying that this was usually in the preceding 3 months (Arthritis Care Res. 2008;59:863-6).

This underuse of contraception is not unique to lupus patients, and there are many reasons why women with rheumatic diseases who are sexually active may not always use adequate contraception. One of these reasons was the lack of time during consultations, which tend to focus on disease management rather than issues such as contraceptive counseling. Other reasons may be misconceptions on fertility or a lack of understanding of the teratogenicity of medications or the effect that hormones may have on disease activity. Women also may be reluctant to take additional medicines or feel uncomfortable discussing the topic with their rheumatologists.

“Patients see their rheumatologist more frequently than any other [health care] provider,” Dr. Chakravarty said, adding that continual follow-up appointments over time provide an opportunity to discuss fertility and changing contraception needs. “Contraception is a component of effective disease management for young women,” she said.

There are many contraceptive methods available, each with pros and cons and varying efficacy, so women have multiple options to choose from to suit their personal preferences and lifestyles. Dr. Chakravarty suggested that, of all the available methods, long-acting reversible contraceptive methods, such as the subdermal implant or intrauterine device, were perhaps the best choice for many women with rheumatic diseases since they are associated with a low rate of accidental pregnancy and after insertion there is little or nothing to do or remember until the devices needed replacing after 3-10 years.

Dr. Monika Østensen of the Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases at St. Olavs Hospital-Trondheim University Hospital, echoed the need for repeated family-planning advice. Of course, pregnancies occur even with the best planning, she said, and the question then is how to manage the rheumatic disease.

The need for treatment will depending on the type of disease, she said, noting that the need generally decreased during pregnancy in women with rheumatoid arthritis (RA) but increased in those with ankylosing spondylitis, most notably in the first and second trimesters (Ann. Rheum. Dis. 2004;63:1212-7). The ideal situation would be to adjust disease-directed therapy if needed before conception, although methotrexate is the only drug with proven teratogenicity that is used for RA and ankylosing spondylitis and that should definitely be stopped, she said.

There is a lot of evidence that methotrexate needs to be stopped before pregnancy. One recent prospective study (Arthritis Rheumatol. 2014;66:1101-10) looked at pregnancy outcomes and methotrexate use and found a high rate of spontaneous abortions if it was used within 10 weeks of conception (14.4%) or in the first trimester (42.5%). The rate of major birth defects was 6.6% if methotrexate was used in early pregnancy, versus 2.9% for women without rheumatic disease or 3.5% in women with rheumatic disease who were not taking the disease-modifying antirheumatic drug (DMARD).

Dr. Østensen advised that, when stopping methotrexate, women should be counseled to wait for one menstrual cycle before attempting to conceive and not to stop therapy without perhaps checking for fertility or switching to another pregnancy-compatible drug. She also stressed that patients who want to become pregnant or who do become pregnant should not immediately stop taking their medication without consulting a rheumatologist. Such an action could result in disease flares, and the aim of therapy should always be to keep the patient in remission or low disease activity and continue drugs that support remission while trying to minimize any likely effects on the fetus.

Leflunomide (Arava), rituximab (Rituxan), abatacept (Orencia), and newer biologics such as tocilizumab (Actemra), ustekinumab (Stelara), and tofacitinb (Xeljanz) are contraindicated because of lack of data on whether they are safe for the fetus. If a woman did become pregnant while taking any of these drugs or even methotrexate, then taking a careful history and performing fetal ultrasound and amniocentesis may be the best approach to determine what action to take and if pregnancy termination should be considered.

Tumor necrosis factor-alpha inhibitors (TNFi), the best-studied biologic DMARDs, can be given before conception and during the first and early second trimester; however, use in late pregnancy requires different considerations because transplacental passage varies based on differences related to their structure. Some TNFis, such as certolizumab pegol (Cimzia), have small affinity to the fetal Fc receptor or no Fc part and show low transplacental passage to the fetus. TNFis that possess an Fc part of immunoglobulin G1, however, allow high amounts of transfer and should be avoided in the third trimester whenever possible, Dr. Østensen said.

Data are sparse on human pregnancy exposure and fetal side effects and outcomes for most other biologics, so decisions to use biologics targeting B-cells, T-cell activation, or cytokines like interleukin (IL)-6, IL-23, IL-17, or IL-1beta must be based on the severity of maternal disease and reserved for cases in which no other safe options are available, Dr. Østensen cautioned.

So how can acute arthritis be treated during pregnancy? Options in RA include NSAIDs, short-term oral prednisone with rapid tapering or intramuscular injection of triamcinolone. Intra-articular steroid injection also might be considered, and TNFi in patients with severe polyarthritis. Spondyloarthritis might be treated with NSAIDs, intramuscular triamcinolone, or intra-articular steroid injection, with TNFi in severe cases.

Newer approaches to managing arthritis during pregnancy are to perhaps prescribe a TNFi with a low propensity for transplacental passage or to use a flexible regimen of TNFi by reducing the dose or prolonging the interval between administrations.

Continuing medications such as hydroxychloroquine, sulfasalazine, or azathioprine might be in some patients’ best interests to support remission and keep disease activity low, Dr. Østensen suggested. She noted that prednisone should be used at a low (5-7.5 mg) dose during pregnancy and that the aim should be to try to slowly reduce the use of pregnancy-compatible medications that are not necessary for continued remission, keeping a close eye on patients’ disease activity to ensure that no flares occur.

Dr. Chakravarty had no financial disclosures. Dr. Østensen reported receiving speaker fees and honoraria from UCB, Roche, AbbVie, MSD, Pfizer, and New Bridge.

ROME – New therapies introduced over the past 15 years have vastly improved the lives of patients with rheumatic diseases but are also creating complex treatment scenarios as more female patients consider starting a family or become pregnant while taking medication. At the European Congress of Rheumatology, experts discussed the importance of contraceptive counseling, pregnancy planning, and how to treat pregnant women with rheumatic diseases.

“Nowadays we have such better treatments for our patients that sexuality and contraception is becoming more and more important,” said Dr. Eliza Chakravarty of the Oklahoma Medical Research Foundation in Oklahoma City. Yet contraception is “quite underused in our patients,” she observed.

©Jupiterimages/thinkstockphotos.com

Indeed, in one study looking at the risk of unintended pregnancy in women with lupus, over half (55%) of the 212 women surveyed admitted that they had unprotected sex at least once, with almost a quarter (23%) saying that this was usually in the preceding 3 months (Arthritis Care Res. 2008;59:863-6).

This underuse of contraception is not unique to lupus patients, and there are many reasons why women with rheumatic diseases who are sexually active may not always use adequate contraception. One of these reasons was the lack of time during consultations, which tend to focus on disease management rather than issues such as contraceptive counseling. Other reasons may be misconceptions on fertility or a lack of understanding of the teratogenicity of medications or the effect that hormones may have on disease activity. Women also may be reluctant to take additional medicines or feel uncomfortable discussing the topic with their rheumatologists.

“Patients see their rheumatologist more frequently than any other [health care] provider,” Dr. Chakravarty said, adding that continual follow-up appointments over time provide an opportunity to discuss fertility and changing contraception needs. “Contraception is a component of effective disease management for young women,” she said.

There are many contraceptive methods available, each with pros and cons and varying efficacy, so women have multiple options to choose from to suit their personal preferences and lifestyles. Dr. Chakravarty suggested that, of all the available methods, long-acting reversible contraceptive methods, such as the subdermal implant or intrauterine device, were perhaps the best choice for many women with rheumatic diseases since they are associated with a low rate of accidental pregnancy and after insertion there is little or nothing to do or remember until the devices needed replacing after 3-10 years.

Dr. Monika Østensen of the Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases at St. Olavs Hospital-Trondheim University Hospital, echoed the need for repeated family-planning advice. Of course, pregnancies occur even with the best planning, she said, and the question then is how to manage the rheumatic disease.

The need for treatment will depending on the type of disease, she said, noting that the need generally decreased during pregnancy in women with rheumatoid arthritis (RA) but increased in those with ankylosing spondylitis, most notably in the first and second trimesters (Ann. Rheum. Dis. 2004;63:1212-7). The ideal situation would be to adjust disease-directed therapy if needed before conception, although methotrexate is the only drug with proven teratogenicity that is used for RA and ankylosing spondylitis and that should definitely be stopped, she said.

There is a lot of evidence that methotrexate needs to be stopped before pregnancy. One recent prospective study (Arthritis Rheumatol. 2014;66:1101-10) looked at pregnancy outcomes and methotrexate use and found a high rate of spontaneous abortions if it was used within 10 weeks of conception (14.4%) or in the first trimester (42.5%). The rate of major birth defects was 6.6% if methotrexate was used in early pregnancy, versus 2.9% for women without rheumatic disease or 3.5% in women with rheumatic disease who were not taking the disease-modifying antirheumatic drug (DMARD).

Dr. Østensen advised that, when stopping methotrexate, women should be counseled to wait for one menstrual cycle before attempting to conceive and not to stop therapy without perhaps checking for fertility or switching to another pregnancy-compatible drug. She also stressed that patients who want to become pregnant or who do become pregnant should not immediately stop taking their medication without consulting a rheumatologist. Such an action could result in disease flares, and the aim of therapy should always be to keep the patient in remission or low disease activity and continue drugs that support remission while trying to minimize any likely effects on the fetus.

Leflunomide (Arava), rituximab (Rituxan), abatacept (Orencia), and newer biologics such as tocilizumab (Actemra), ustekinumab (Stelara), and tofacitinb (Xeljanz) are contraindicated because of lack of data on whether they are safe for the fetus. If a woman did become pregnant while taking any of these drugs or even methotrexate, then taking a careful history and performing fetal ultrasound and amniocentesis may be the best approach to determine what action to take and if pregnancy termination should be considered.

Tumor necrosis factor-alpha inhibitors (TNFi), the best-studied biologic DMARDs, can be given before conception and during the first and early second trimester; however, use in late pregnancy requires different considerations because transplacental passage varies based on differences related to their structure. Some TNFis, such as certolizumab pegol (Cimzia), have small affinity to the fetal Fc receptor or no Fc part and show low transplacental passage to the fetus. TNFis that possess an Fc part of immunoglobulin G1, however, allow high amounts of transfer and should be avoided in the third trimester whenever possible, Dr. Østensen said.

Data are sparse on human pregnancy exposure and fetal side effects and outcomes for most other biologics, so decisions to use biologics targeting B-cells, T-cell activation, or cytokines like interleukin (IL)-6, IL-23, IL-17, or IL-1beta must be based on the severity of maternal disease and reserved for cases in which no other safe options are available, Dr. Østensen cautioned.

So how can acute arthritis be treated during pregnancy? Options in RA include NSAIDs, short-term oral prednisone with rapid tapering or intramuscular injection of triamcinolone. Intra-articular steroid injection also might be considered, and TNFi in patients with severe polyarthritis. Spondyloarthritis might be treated with NSAIDs, intramuscular triamcinolone, or intra-articular steroid injection, with TNFi in severe cases.

Newer approaches to managing arthritis during pregnancy are to perhaps prescribe a TNFi with a low propensity for transplacental passage or to use a flexible regimen of TNFi by reducing the dose or prolonging the interval between administrations.

Continuing medications such as hydroxychloroquine, sulfasalazine, or azathioprine might be in some patients’ best interests to support remission and keep disease activity low, Dr. Østensen suggested. She noted that prednisone should be used at a low (5-7.5 mg) dose during pregnancy and that the aim should be to try to slowly reduce the use of pregnancy-compatible medications that are not necessary for continued remission, keeping a close eye on patients’ disease activity to ensure that no flares occur.

Dr. Chakravarty had no financial disclosures. Dr. Østensen reported receiving speaker fees and honoraria from UCB, Roche, AbbVie, MSD, Pfizer, and New Bridge.

ROME – Reassuring new data from the German biologics registry RABBIT presented at the European Congress of Rheumatology indicate that exposure to biologic therapies around the time of conception does not increase the risk of malformations or other harmful neonatal consequences.

Observational studies suggest that biologic disease-modifying antirheumatic drugs (DMARDs) are safe to use in patients with rheumatoid arthritis until conception, but questions remain about their influence on birth outcomes, Dr. Anja Strangfeld of the German Rheumatism Research Center, Berlin, and one of the principal investigators for RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy), said in a precongress interview. Dr. Strangfeld also noted that questions remained on the course of RA during pregnancy in women who stopped biologic therapy in the first trimester, and how to treat high disease activity, including the use of glucocorticoids.

Her coprincipal investigator, Dr. Angela Zink, also of the German Rheumatism Research Center, presented the new findings during the scientific sessions, which considered 106 pregnancies in 88 women aged 45 years or younger that had occurred between 2001 and the end of 2014. Of these, 42 had occurred in the preceding 3 years.

Among the 38 women who stopped biologics before conception, therapies included rituximab (n = 13), etanercept (n = 12), adalimumab (n = 9), tocilizumab (n = 2), and infliximab (n = 2). Etanercept and adalimumab were the most common therapies among those using biologics at conception, administered in 29 and 11 patients, respectively.

The study identified five spontaneous abortions in 38 pregnancies (13%) in which biologic DMARD infusions or injections were stopped at least 4 weeks before conception and 11 spontaneous abortions among 57 pregnancies (19%) exposed to biologic DMARDs at conception. A total of 11 patients were biologic naive, and no spontaneous abortions were observed. Reassuringly, the rates of spontaneous abortions were within the range of about 15%-20% observed in the general public.

Induced abortions were decided on in 4 of the 106 pregnancies. Three occurred in the 38 women who stopped biologic therapy before conception, including one abortion due to trisomy 21, and the other one was in a women who had been taking biologic DMARD therapy at conception.

The live birth rate was 100% for the biologic-naive women, and 79% for both women who stopped biologic DMARDs before conception and those who had been taking them at conception.

Four congenital defects were reported in live-born children: one anal atresia with urogenital malformation (last adalimumab injection 4 weeks before conception), one congenital nystagmus after preterm birth (last adalimumab injection > 6 months before conception), and one case of spina bifida (last etanercept injection > 9 months before conception). There was also one case of talipes in a child whose mother reported also having talipes and had been taking adalimumab at time of conception.

Although the analysis includes a limited sample of pregnancies, these data confirm previous reports and show no increased risk of major malformations or other harmful consequences in patients exposed to biologic therapy around conception.

“We found that, in patients with long-standing rheumatic disease, remission during pregnancy is rarely reached,” Dr. Zink observed. In fact, “disease activity increased during pregnancy in a considerable proportion of the patients,” she added. This is in contrast to other studies and experience, however, she acknowledged, where disease activity has been shown to reduce during pregnancy.

Of 23 patients who were in already in remission before conception, 10 (43%) remained in remission during their pregnancies. Of the 49 patients who had not been in remission before pregnancy, only seven (14%) went into remission during pregnancy.

Dr. Zink noted that a new German pregnancy registry, RHEKISS, will start recruitment in July 2015 to observe treatment needs from the first desire to conceive or early pregnancy (first trimester) until the child’s second birthday. This register will initially include women with any inflammatory rheumatic disease but will later also include male patients whose partner is pregnant.

In a separate presentation, Dr. John J. Cush of Baylor Research Institute and Baylor University Medical Center in Dallas reported other data on the safety of tumor necrosis factor inhibitors (TNFis) in pregnancy. He presented prospectively collected data on pregnancy outcomes in 78 women with rheumatic disease and 148 women with other inflammatory diseases, such as Crohn’s disease, who were exposed to certolizumab pegol (Cimzia) from the manufacturer UCB Pharma’s global safety database.

He observed that because certolizumab’s structure lacks an Fc region, it was potentially a more favorable anti-TNF therapy to use during pregnancy than etanercept, infliximab, adalimumab, or golimumab because it was thought to be less likely to cross the placental barrier and affect the developing fetus.

“Live births were reported for the majority of pregnancies of women with rheumatic diseases following maternal certolizumab exposure,” Dr. Cush said.

Almost three-quarters (73.1%) of the 78 women with rheumatic disease had a live birth with no congenital malformations. Around 5% of live births were associated with congenital malformations, and the rates of spontaneous and induced abortions were a respective 11.5% and 14.1%.

In the 132 women with nonrheumatic inflammatory diseases, there were 86.6% live births without and 4.4% with congenital abnormalities and 9.1% and 5.3% spontaneous and induced abortions.

For all indications, there were 12 congenital malformations from 254 live births. These included anal fistula, polydactyl left hand, posterior ankyloglossia, renal cyst for which no treatment was needed, pyloric stenosis, club foot, and left-sided vesicoureteral reflux.

Dr. Cush noted that one neonate in a set of premature twins delivered at 26 weeks died due to brain damage and pneumoperitoneum.

Importantly, the data were “encouraging” he said and “suggest that certolizumab exposure in utero, including the first trimester of exposure, does not adversely affect pregnancy outcome.”

The German biologics registry RABBIT is supported by grants from AbbVie, BMS, Celltrion, Hospira, MSD, Pfizer, Roche, and UCB. Dr. Strangfeld reported having no disclosures. Dr. Zink has received speaker fees from AbbVie, BMS, MSD, Pfizer, Sanofi Aventis, Roche and USB. Dr. Cush disclosed receiving research grants from Pfizer, Celgene, CORRONA, Amgen, the National Institutes of Health, Novartis, and UCB.

*Correction, 6/24/2015: An earlier version of this article contained a misspelled word in the headline.

ROME – Reassuring new data from the German biologics registry RABBIT presented at the European Congress of Rheumatology indicate that exposure to biologic therapies around the time of conception does not increase the risk of malformations or other harmful neonatal consequences.

Observational studies suggest that biologic disease-modifying antirheumatic drugs (DMARDs) are safe to use in patients with rheumatoid arthritis until conception, but questions remain about their influence on birth outcomes, Dr. Anja Strangfeld of the German Rheumatism Research Center, Berlin, and one of the principal investigators for RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy), said in a precongress interview. Dr. Strangfeld also noted that questions remained on the course of RA during pregnancy in women who stopped biologic therapy in the first trimester, and how to treat high disease activity, including the use of glucocorticoids.

Her coprincipal investigator, Dr. Angela Zink, also of the German Rheumatism Research Center, presented the new findings during the scientific sessions, which considered 106 pregnancies in 88 women aged 45 years or younger that had occurred between 2001 and the end of 2014. Of these, 42 had occurred in the preceding 3 years.

Among the 38 women who stopped biologics before conception, therapies included rituximab (n = 13), etanercept (n = 12), adalimumab (n = 9), tocilizumab (n = 2), and infliximab (n = 2). Etanercept and adalimumab were the most common therapies among those using biologics at conception, administered in 29 and 11 patients, respectively.

The study identified five spontaneous abortions in 38 pregnancies (13%) in which biologic DMARD infusions or injections were stopped at least 4 weeks before conception and 11 spontaneous abortions among 57 pregnancies (19%) exposed to biologic DMARDs at conception. A total of 11 patients were biologic naive, and no spontaneous abortions were observed. Reassuringly, the rates of spontaneous abortions were within the range of about 15%-20% observed in the general public.

Induced abortions were decided on in 4 of the 106 pregnancies. Three occurred in the 38 women who stopped biologic therapy before conception, including one abortion due to trisomy 21, and the other one was in a women who had been taking biologic DMARD therapy at conception.

The live birth rate was 100% for the biologic-naive women, and 79% for both women who stopped biologic DMARDs before conception and those who had been taking them at conception.

Four congenital defects were reported in live-born children: one anal atresia with urogenital malformation (last adalimumab injection 4 weeks before conception), one congenital nystagmus after preterm birth (last adalimumab injection > 6 months before conception), and one case of spina bifida (last etanercept injection > 9 months before conception). There was also one case of talipes in a child whose mother reported also having talipes and had been taking adalimumab at time of conception.

Although the analysis includes a limited sample of pregnancies, these data confirm previous reports and show no increased risk of major malformations or other harmful consequences in patients exposed to biologic therapy around conception.

“We found that, in patients with long-standing rheumatic disease, remission during pregnancy is rarely reached,” Dr. Zink observed. In fact, “disease activity increased during pregnancy in a considerable proportion of the patients,” she added. This is in contrast to other studies and experience, however, she acknowledged, where disease activity has been shown to reduce during pregnancy.

Of 23 patients who were in already in remission before conception, 10 (43%) remained in remission during their pregnancies. Of the 49 patients who had not been in remission before pregnancy, only seven (14%) went into remission during pregnancy.

Dr. Zink noted that a new German pregnancy registry, RHEKISS, will start recruitment in July 2015 to observe treatment needs from the first desire to conceive or early pregnancy (first trimester) until the child’s second birthday. This register will initially include women with any inflammatory rheumatic disease but will later also include male patients whose partner is pregnant.

In a separate presentation, Dr. John J. Cush of Baylor Research Institute and Baylor University Medical Center in Dallas reported other data on the safety of tumor necrosis factor inhibitors (TNFis) in pregnancy. He presented prospectively collected data on pregnancy outcomes in 78 women with rheumatic disease and 148 women with other inflammatory diseases, such as Crohn’s disease, who were exposed to certolizumab pegol (Cimzia) from the manufacturer UCB Pharma’s global safety database.

He observed that because certolizumab’s structure lacks an Fc region, it was potentially a more favorable anti-TNF therapy to use during pregnancy than etanercept, infliximab, adalimumab, or golimumab because it was thought to be less likely to cross the placental barrier and affect the developing fetus.

“Live births were reported for the majority of pregnancies of women with rheumatic diseases following maternal certolizumab exposure,” Dr. Cush said.

Almost three-quarters (73.1%) of the 78 women with rheumatic disease had a live birth with no congenital malformations. Around 5% of live births were associated with congenital malformations, and the rates of spontaneous and induced abortions were a respective 11.5% and 14.1%.

In the 132 women with nonrheumatic inflammatory diseases, there were 86.6% live births without and 4.4% with congenital abnormalities and 9.1% and 5.3% spontaneous and induced abortions.

For all indications, there were 12 congenital malformations from 254 live births. These included anal fistula, polydactyl left hand, posterior ankyloglossia, renal cyst for which no treatment was needed, pyloric stenosis, club foot, and left-sided vesicoureteral reflux.

Dr. Cush noted that one neonate in a set of premature twins delivered at 26 weeks died due to brain damage and pneumoperitoneum.

Importantly, the data were “encouraging” he said and “suggest that certolizumab exposure in utero, including the first trimester of exposure, does not adversely affect pregnancy outcome.”

The German biologics registry RABBIT is supported by grants from AbbVie, BMS, Celltrion, Hospira, MSD, Pfizer, Roche, and UCB. Dr. Strangfeld reported having no disclosures. Dr. Zink has received speaker fees from AbbVie, BMS, MSD, Pfizer, Sanofi Aventis, Roche and USB. Dr. Cush disclosed receiving research grants from Pfizer, Celgene, CORRONA, Amgen, the National Institutes of Health, Novartis, and UCB.

*Correction, 6/24/2015: An earlier version of this article contained a misspelled word in the headline.

ROME – Reassuring new data from the German biologics registry RABBIT presented at the European Congress of Rheumatology indicate that exposure to biologic therapies around the time of conception does not increase the risk of malformations or other harmful neonatal consequences.

Observational studies suggest that biologic disease-modifying antirheumatic drugs (DMARDs) are safe to use in patients with rheumatoid arthritis until conception, but questions remain about their influence on birth outcomes, Dr. Anja Strangfeld of the German Rheumatism Research Center, Berlin, and one of the principal investigators for RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy), said in a precongress interview. Dr. Strangfeld also noted that questions remained on the course of RA during pregnancy in women who stopped biologic therapy in the first trimester, and how to treat high disease activity, including the use of glucocorticoids.

Her coprincipal investigator, Dr. Angela Zink, also of the German Rheumatism Research Center, presented the new findings during the scientific sessions, which considered 106 pregnancies in 88 women aged 45 years or younger that had occurred between 2001 and the end of 2014. Of these, 42 had occurred in the preceding 3 years.

Among the 38 women who stopped biologics before conception, therapies included rituximab (n = 13), etanercept (n = 12), adalimumab (n = 9), tocilizumab (n = 2), and infliximab (n = 2). Etanercept and adalimumab were the most common therapies among those using biologics at conception, administered in 29 and 11 patients, respectively.

The study identified five spontaneous abortions in 38 pregnancies (13%) in which biologic DMARD infusions or injections were stopped at least 4 weeks before conception and 11 spontaneous abortions among 57 pregnancies (19%) exposed to biologic DMARDs at conception. A total of 11 patients were biologic naive, and no spontaneous abortions were observed. Reassuringly, the rates of spontaneous abortions were within the range of about 15%-20% observed in the general public.

Induced abortions were decided on in 4 of the 106 pregnancies. Three occurred in the 38 women who stopped biologic therapy before conception, including one abortion due to trisomy 21, and the other one was in a women who had been taking biologic DMARD therapy at conception.

The live birth rate was 100% for the biologic-naive women, and 79% for both women who stopped biologic DMARDs before conception and those who had been taking them at conception.

Four congenital defects were reported in live-born children: one anal atresia with urogenital malformation (last adalimumab injection 4 weeks before conception), one congenital nystagmus after preterm birth (last adalimumab injection > 6 months before conception), and one case of spina bifida (last etanercept injection > 9 months before conception). There was also one case of talipes in a child whose mother reported also having talipes and had been taking adalimumab at time of conception.

Although the analysis includes a limited sample of pregnancies, these data confirm previous reports and show no increased risk of major malformations or other harmful consequences in patients exposed to biologic therapy around conception.

“We found that, in patients with long-standing rheumatic disease, remission during pregnancy is rarely reached,” Dr. Zink observed. In fact, “disease activity increased during pregnancy in a considerable proportion of the patients,” she added. This is in contrast to other studies and experience, however, she acknowledged, where disease activity has been shown to reduce during pregnancy.

Of 23 patients who were in already in remission before conception, 10 (43%) remained in remission during their pregnancies. Of the 49 patients who had not been in remission before pregnancy, only seven (14%) went into remission during pregnancy.

Dr. Zink noted that a new German pregnancy registry, RHEKISS, will start recruitment in July 2015 to observe treatment needs from the first desire to conceive or early pregnancy (first trimester) until the child’s second birthday. This register will initially include women with any inflammatory rheumatic disease but will later also include male patients whose partner is pregnant.

In a separate presentation, Dr. John J. Cush of Baylor Research Institute and Baylor University Medical Center in Dallas reported other data on the safety of tumor necrosis factor inhibitors (TNFis) in pregnancy. He presented prospectively collected data on pregnancy outcomes in 78 women with rheumatic disease and 148 women with other inflammatory diseases, such as Crohn’s disease, who were exposed to certolizumab pegol (Cimzia) from the manufacturer UCB Pharma’s global safety database.

He observed that because certolizumab’s structure lacks an Fc region, it was potentially a more favorable anti-TNF therapy to use during pregnancy than etanercept, infliximab, adalimumab, or golimumab because it was thought to be less likely to cross the placental barrier and affect the developing fetus.

“Live births were reported for the majority of pregnancies of women with rheumatic diseases following maternal certolizumab exposure,” Dr. Cush said.

Almost three-quarters (73.1%) of the 78 women with rheumatic disease had a live birth with no congenital malformations. Around 5% of live births were associated with congenital malformations, and the rates of spontaneous and induced abortions were a respective 11.5% and 14.1%.

In the 132 women with nonrheumatic inflammatory diseases, there were 86.6% live births without and 4.4% with congenital abnormalities and 9.1% and 5.3% spontaneous and induced abortions.

For all indications, there were 12 congenital malformations from 254 live births. These included anal fistula, polydactyl left hand, posterior ankyloglossia, renal cyst for which no treatment was needed, pyloric stenosis, club foot, and left-sided vesicoureteral reflux.

Dr. Cush noted that one neonate in a set of premature twins delivered at 26 weeks died due to brain damage and pneumoperitoneum.

Importantly, the data were “encouraging” he said and “suggest that certolizumab exposure in utero, including the first trimester of exposure, does not adversely affect pregnancy outcome.”

The German biologics registry RABBIT is supported by grants from AbbVie, BMS, Celltrion, Hospira, MSD, Pfizer, Roche, and UCB. Dr. Strangfeld reported having no disclosures. Dr. Zink has received speaker fees from AbbVie, BMS, MSD, Pfizer, Sanofi Aventis, Roche and USB. Dr. Cush disclosed receiving research grants from Pfizer, Celgene, CORRONA, Amgen, the National Institutes of Health, Novartis, and UCB.

*Correction, 6/24/2015: An earlier version of this article contained a misspelled word in the headline.

ROME – Updated expert recommendations from the European League Against Rheumatism for the treatment of systemic sclerosis will focus on several new treatment options, although the use of biologic agents is not included in detail because there are still too few data on these drugs to give firm guidance on their use.

The EULAR Scleroderma Trials and Research group (EUSTAR) recommendations for the treatment of scleroderma were first published 6 years ago (Ann. Rheum. Dis. 2009;68:620-8) and considered data through December 2006.

© Eveline Perroud

“Since then, a number of new drugs have become available and new and important information has been published concerning treatments already known before,” said Dr. Otylia Kowal-Bielecka of the Medical University of Bialystok, Poland, who discussed some of the main highlights of the revised recommendations (Ann. Rheum. Dis. 2015;74:90-1) at the European Congress of Rheumatology.

Scleroderma experts from all EUSTAR centers were invited to participate in the update and submit questions that could form the basis of the updated recommendations. From a total of 170 questions suggested, 46 questions concerning 23 treatment categories were researched in more depth via a systematic review of the literature that considered papers published through September 2014. A task force of more than 30 experts from Europe and the United States, two patients with scleroderma, and a clinical epidemiologist then met in October 2014 to discuss and formulate the final 16 recommendations.

The guidance covers the same main organ categories as the 2009 iteration – Raynaud phenomenon (RP), digital ulcers, pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis, and systemic sclerosis (SSc)-related gastrointestinal (GI) disease – Dr. Kowal-Bielecka observed, but the main difference is that many of the treatment options have been updated or reworded.

For instance, phosphodiesterase (PDE)-5 inhibitors and fluoxetine (Prozac) have been added to the treatment options for SSc-RP, which previously only included dihydropyridine-type calcium antagonists and intravenous iloprost. The latter is recommended after oral therapy. Evidence for the use of fluoxetine is weaker than for the PDE-5 inhibitors, but it might be worth considering in a patient with SSc-RP attacks. PDE-5 inhibitors have also been added to the list of options for digital ulcers. For PAH, where sildenafil (Viagra) was already recommended, tadalafil (Cialis) had been specifically included.

Intravenous iloprost and the endothelin-receptor antagonist (ERA) bosentan (Tracleer) continue to be recommended for the management of digital ulcers. The recommendation on bosentan has been amended based on new data from two “high-quality,” randomized, clinical trials and now considers the whole patient population rather than just those with disseminated disease, Dr. Kowal-Bielecka noted. The new statement recommends considering bosentan to reduce the number of new digital ulcers, especially in patients with multiple ulcers that might not be responding to calcium-channel blockers, PDE-5 inhibitors, and iloprost.

The area with the most changes is the treatment of PAH, with many new drugs now recommended, including tadalafil, riociguat (Adempas), ambrisentan (Letairis), and macitentan (Opsumit), as well as more intravenous prostacyclin analogues such as epoprostenol (Flolan).

Hematopoietic stem cell transplantation (HSCT) has been added to the list of options for managing skin and lung disease, which includes methotrexate for skin manifestations of early diffuse SSc and cyclophosphamide for interstitial lung disease. HSCT is only for selected patients who have progressive scleroderma and were at risk of organ failure, Dr. Kowal-Bielecka qualified. “In view of the high risk of treatment-related side effects and of early treatment-related mortality, careful selection of SSc patients for this kind of treatment and experience of medical team are of key importance,” part of the draft recommendation reads.

Evidence from several descriptive cohort studies support the use of angiotensin-converting enzyme inhibitors for scleroderma renal crisis, and the expert opinion is that they should be used immediately. *The recommendations continue to advise against using glucocorticoids in this patient population, based on retrospective study data. It is important to monitor patients’ blood pressure and renal function while on treatment with steroids.

Recommendations have not changed for the management of SSc-related GI disease, but have been reworded slightly to recommend prokinetic drugs and the intermittent or rotating use of antibiotics.

“Several biologics were considered as potentially interesting, we had tocilizumab [Actemra], rituximab [Rituxan], and TNF-alpha blockers on our list, and they also underwent the systematic literature research and review process,” Dr. Kowal-Bielecka said in an interview. “However, the evidence available at the moment was considered by the expert panel to be insufficient to provide any recommendations,” she said.

Dr. Kowal-Bielecka also noted that the expert panel had developed a research agenda for a list of drugs that are considered promising and which should be more carefully looked at in future trials.

“We believe that these guidelines provide knowledge to the broad community of rheumatologists who do not always have time to follow new developments in the published literature,” she observed. In turn, it is hoped that the recommendations will help rheumatologists to manage their patients with SSc better, based on currently available evidence.

The draft recommendations are close to being finalized and undergoing expert review by the EUSTAR task force before publication hopefully later this year, Dr. Kowal-Bielecka said.

The project is funded by a research grant of EULAR to the EUSTAR SSc recommendation group. Dr. Kowal-Bielecka is a member of speaker bureaus for AbbVie, Actelion, Pfizer, and Roche.

*Correction, 8/6/2015: An earlier version of this article misstated the recommendation given for glucocorticoid use in scleroderma renal crisis.

ROME – Updated expert recommendations from the European League Against Rheumatism for the treatment of systemic sclerosis will focus on several new treatment options, although the use of biologic agents is not included in detail because there are still too few data on these drugs to give firm guidance on their use.

The EULAR Scleroderma Trials and Research group (EUSTAR) recommendations for the treatment of scleroderma were first published 6 years ago (Ann. Rheum. Dis. 2009;68:620-8) and considered data through December 2006.

© Eveline Perroud

“Since then, a number of new drugs have become available and new and important information has been published concerning treatments already known before,” said Dr. Otylia Kowal-Bielecka of the Medical University of Bialystok, Poland, who discussed some of the main highlights of the revised recommendations (Ann. Rheum. Dis. 2015;74:90-1) at the European Congress of Rheumatology.

Scleroderma experts from all EUSTAR centers were invited to participate in the update and submit questions that could form the basis of the updated recommendations. From a total of 170 questions suggested, 46 questions concerning 23 treatment categories were researched in more depth via a systematic review of the literature that considered papers published through September 2014. A task force of more than 30 experts from Europe and the United States, two patients with scleroderma, and a clinical epidemiologist then met in October 2014 to discuss and formulate the final 16 recommendations.

The guidance covers the same main organ categories as the 2009 iteration – Raynaud phenomenon (RP), digital ulcers, pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis, and systemic sclerosis (SSc)-related gastrointestinal (GI) disease – Dr. Kowal-Bielecka observed, but the main difference is that many of the treatment options have been updated or reworded.

For instance, phosphodiesterase (PDE)-5 inhibitors and fluoxetine (Prozac) have been added to the treatment options for SSc-RP, which previously only included dihydropyridine-type calcium antagonists and intravenous iloprost. The latter is recommended after oral therapy. Evidence for the use of fluoxetine is weaker than for the PDE-5 inhibitors, but it might be worth considering in a patient with SSc-RP attacks. PDE-5 inhibitors have also been added to the list of options for digital ulcers. For PAH, where sildenafil (Viagra) was already recommended, tadalafil (Cialis) had been specifically included.

Intravenous iloprost and the endothelin-receptor antagonist (ERA) bosentan (Tracleer) continue to be recommended for the management of digital ulcers. The recommendation on bosentan has been amended based on new data from two “high-quality,” randomized, clinical trials and now considers the whole patient population rather than just those with disseminated disease, Dr. Kowal-Bielecka noted. The new statement recommends considering bosentan to reduce the number of new digital ulcers, especially in patients with multiple ulcers that might not be responding to calcium-channel blockers, PDE-5 inhibitors, and iloprost.

The area with the most changes is the treatment of PAH, with many new drugs now recommended, including tadalafil, riociguat (Adempas), ambrisentan (Letairis), and macitentan (Opsumit), as well as more intravenous prostacyclin analogues such as epoprostenol (Flolan).

Hematopoietic stem cell transplantation (HSCT) has been added to the list of options for managing skin and lung disease, which includes methotrexate for skin manifestations of early diffuse SSc and cyclophosphamide for interstitial lung disease. HSCT is only for selected patients who have progressive scleroderma and were at risk of organ failure, Dr. Kowal-Bielecka qualified. “In view of the high risk of treatment-related side effects and of early treatment-related mortality, careful selection of SSc patients for this kind of treatment and experience of medical team are of key importance,” part of the draft recommendation reads.

Evidence from several descriptive cohort studies support the use of angiotensin-converting enzyme inhibitors for scleroderma renal crisis, and the expert opinion is that they should be used immediately. *The recommendations continue to advise against using glucocorticoids in this patient population, based on retrospective study data. It is important to monitor patients’ blood pressure and renal function while on treatment with steroids.

Recommendations have not changed for the management of SSc-related GI disease, but have been reworded slightly to recommend prokinetic drugs and the intermittent or rotating use of antibiotics.

“Several biologics were considered as potentially interesting, we had tocilizumab [Actemra], rituximab [Rituxan], and TNF-alpha blockers on our list, and they also underwent the systematic literature research and review process,” Dr. Kowal-Bielecka said in an interview. “However, the evidence available at the moment was considered by the expert panel to be insufficient to provide any recommendations,” she said.

Dr. Kowal-Bielecka also noted that the expert panel had developed a research agenda for a list of drugs that are considered promising and which should be more carefully looked at in future trials.

“We believe that these guidelines provide knowledge to the broad community of rheumatologists who do not always have time to follow new developments in the published literature,” she observed. In turn, it is hoped that the recommendations will help rheumatologists to manage their patients with SSc better, based on currently available evidence.

The draft recommendations are close to being finalized and undergoing expert review by the EUSTAR task force before publication hopefully later this year, Dr. Kowal-Bielecka said.

The project is funded by a research grant of EULAR to the EUSTAR SSc recommendation group. Dr. Kowal-Bielecka is a member of speaker bureaus for AbbVie, Actelion, Pfizer, and Roche.

*Correction, 8/6/2015: An earlier version of this article misstated the recommendation given for glucocorticoid use in scleroderma renal crisis.

ROME – Updated expert recommendations from the European League Against Rheumatism for the treatment of systemic sclerosis will focus on several new treatment options, although the use of biologic agents is not included in detail because there are still too few data on these drugs to give firm guidance on their use.

The EULAR Scleroderma Trials and Research group (EUSTAR) recommendations for the treatment of scleroderma were first published 6 years ago (Ann. Rheum. Dis. 2009;68:620-8) and considered data through December 2006.

© Eveline Perroud

“Since then, a number of new drugs have become available and new and important information has been published concerning treatments already known before,” said Dr. Otylia Kowal-Bielecka of the Medical University of Bialystok, Poland, who discussed some of the main highlights of the revised recommendations (Ann. Rheum. Dis. 2015;74:90-1) at the European Congress of Rheumatology.

Scleroderma experts from all EUSTAR centers were invited to participate in the update and submit questions that could form the basis of the updated recommendations. From a total of 170 questions suggested, 46 questions concerning 23 treatment categories were researched in more depth via a systematic review of the literature that considered papers published through September 2014. A task force of more than 30 experts from Europe and the United States, two patients with scleroderma, and a clinical epidemiologist then met in October 2014 to discuss and formulate the final 16 recommendations.

The guidance covers the same main organ categories as the 2009 iteration – Raynaud phenomenon (RP), digital ulcers, pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis, and systemic sclerosis (SSc)-related gastrointestinal (GI) disease – Dr. Kowal-Bielecka observed, but the main difference is that many of the treatment options have been updated or reworded.

For instance, phosphodiesterase (PDE)-5 inhibitors and fluoxetine (Prozac) have been added to the treatment options for SSc-RP, which previously only included dihydropyridine-type calcium antagonists and intravenous iloprost. The latter is recommended after oral therapy. Evidence for the use of fluoxetine is weaker than for the PDE-5 inhibitors, but it might be worth considering in a patient with SSc-RP attacks. PDE-5 inhibitors have also been added to the list of options for digital ulcers. For PAH, where sildenafil (Viagra) was already recommended, tadalafil (Cialis) had been specifically included.

Intravenous iloprost and the endothelin-receptor antagonist (ERA) bosentan (Tracleer) continue to be recommended for the management of digital ulcers. The recommendation on bosentan has been amended based on new data from two “high-quality,” randomized, clinical trials and now considers the whole patient population rather than just those with disseminated disease, Dr. Kowal-Bielecka noted. The new statement recommends considering bosentan to reduce the number of new digital ulcers, especially in patients with multiple ulcers that might not be responding to calcium-channel blockers, PDE-5 inhibitors, and iloprost.

The area with the most changes is the treatment of PAH, with many new drugs now recommended, including tadalafil, riociguat (Adempas), ambrisentan (Letairis), and macitentan (Opsumit), as well as more intravenous prostacyclin analogues such as epoprostenol (Flolan).

Hematopoietic stem cell transplantation (HSCT) has been added to the list of options for managing skin and lung disease, which includes methotrexate for skin manifestations of early diffuse SSc and cyclophosphamide for interstitial lung disease. HSCT is only for selected patients who have progressive scleroderma and were at risk of organ failure, Dr. Kowal-Bielecka qualified. “In view of the high risk of treatment-related side effects and of early treatment-related mortality, careful selection of SSc patients for this kind of treatment and experience of medical team are of key importance,” part of the draft recommendation reads.

Evidence from several descriptive cohort studies support the use of angiotensin-converting enzyme inhibitors for scleroderma renal crisis, and the expert opinion is that they should be used immediately. *The recommendations continue to advise against using glucocorticoids in this patient population, based on retrospective study data. It is important to monitor patients’ blood pressure and renal function while on treatment with steroids.

Recommendations have not changed for the management of SSc-related GI disease, but have been reworded slightly to recommend prokinetic drugs and the intermittent or rotating use of antibiotics.

“Several biologics were considered as potentially interesting, we had tocilizumab [Actemra], rituximab [Rituxan], and TNF-alpha blockers on our list, and they also underwent the systematic literature research and review process,” Dr. Kowal-Bielecka said in an interview. “However, the evidence available at the moment was considered by the expert panel to be insufficient to provide any recommendations,” she said.

Dr. Kowal-Bielecka also noted that the expert panel had developed a research agenda for a list of drugs that are considered promising and which should be more carefully looked at in future trials.

“We believe that these guidelines provide knowledge to the broad community of rheumatologists who do not always have time to follow new developments in the published literature,” she observed. In turn, it is hoped that the recommendations will help rheumatologists to manage their patients with SSc better, based on currently available evidence.

The draft recommendations are close to being finalized and undergoing expert review by the EUSTAR task force before publication hopefully later this year, Dr. Kowal-Bielecka said.

The project is funded by a research grant of EULAR to the EUSTAR SSc recommendation group. Dr. Kowal-Bielecka is a member of speaker bureaus for AbbVie, Actelion, Pfizer, and Roche.

*Correction, 8/6/2015: An earlier version of this article misstated the recommendation given for glucocorticoid use in scleroderma renal crisis.

Systemic lupus erythematosus patients who have just started drug therapy are at greater risk for needing acute care and possible hospitalization if they are nonadherent, based on an analysis of U.S. Medicaid beneficiaries.

Data on 9,600 new hydroxychloroquine (HCQ) and 3,829 new oral immunosuppressive medication users showed that patients who were nonadherent to their medication were 55% and 64% more likely, respectively, than those who were adherent to visit an emergency department. They also were 37% and 67% more likely to be admitted to hospital. This was after multivariate adjustment for sociodemographic factors and comorbidities.

“We also demonstrated that individuals with the poorest level of adherence had the highest rates of acute care utilization,” said lead study author Dr. Candace H. Feldman of Brigham and Women’s Hospital, Boston, and associates (Arthritis Care Res. 2015 June 19 [doi:10.1002/acr.22636]).

In addition, “moderate nonadherence was also associated with statistically significant increases in utilization” for all categories except HCQ SLE-related hospitalizations, they added.

The investigators suggested that this increased acute care utilization could represent “an opportunity to intervene to reduce avoidable morbidity and health care costs by improving adherence behavior.”

Systemic lupus erythematosus patients who have just started drug therapy are at greater risk for needing acute care and possible hospitalization if they are nonadherent, based on an analysis of U.S. Medicaid beneficiaries.

Data on 9,600 new hydroxychloroquine (HCQ) and 3,829 new oral immunosuppressive medication users showed that patients who were nonadherent to their medication were 55% and 64% more likely, respectively, than those who were adherent to visit an emergency department. They also were 37% and 67% more likely to be admitted to hospital. This was after multivariate adjustment for sociodemographic factors and comorbidities.

“We also demonstrated that individuals with the poorest level of adherence had the highest rates of acute care utilization,” said lead study author Dr. Candace H. Feldman of Brigham and Women’s Hospital, Boston, and associates (Arthritis Care Res. 2015 June 19 [doi:10.1002/acr.22636]).

In addition, “moderate nonadherence was also associated with statistically significant increases in utilization” for all categories except HCQ SLE-related hospitalizations, they added.

The investigators suggested that this increased acute care utilization could represent “an opportunity to intervene to reduce avoidable morbidity and health care costs by improving adherence behavior.”

Systemic lupus erythematosus patients who have just started drug therapy are at greater risk for needing acute care and possible hospitalization if they are nonadherent, based on an analysis of U.S. Medicaid beneficiaries.

Data on 9,600 new hydroxychloroquine (HCQ) and 3,829 new oral immunosuppressive medication users showed that patients who were nonadherent to their medication were 55% and 64% more likely, respectively, than those who were adherent to visit an emergency department. They also were 37% and 67% more likely to be admitted to hospital. This was after multivariate adjustment for sociodemographic factors and comorbidities.

“We also demonstrated that individuals with the poorest level of adherence had the highest rates of acute care utilization,” said lead study author Dr. Candace H. Feldman of Brigham and Women’s Hospital, Boston, and associates (Arthritis Care Res. 2015 June 19 [doi:10.1002/acr.22636]).

In addition, “moderate nonadherence was also associated with statistically significant increases in utilization” for all categories except HCQ SLE-related hospitalizations, they added.

The investigators suggested that this increased acute care utilization could represent “an opportunity to intervene to reduce avoidable morbidity and health care costs by improving adherence behavior.”

Targeting natural killer T cells might help prevent bone destruction in rheumatoid arthritis, the results of a preclinical study suggest.

Natural killer T (NKT) cells stimulated by the glycolipid alpha-galactosylceramide (alphaGalCer) were found to have a regulatory effect on the development of osteoclasts, a type of bone cell that resorbs bone and is integral to bone repair and maintenance. These cells could have a protective effect on inflammatory bone destruction, the research team suggested after also finding that the cells’ effects were diminished in patients with RA versus healthy controls.

Hye-Mi Jin of the department of rheumatology at Chonnam National University Medical School and Hospital in Gwangju, South Korea, and associates isolated and cultured NKT cells from 25 subjects with and 15 without RA and performed in vitro experiments to investigate the role played by NKT cells in osteoclastogenesis. They also looked at the in vivo effects of the alphaGalCer-stimulated cells in a mouse model of collagen-induced arthritis (Arthritis Rheumatol. 2015 June 19 [doi:10.1002/art.39244]).

The in vitro studies showed that alphaGalCer significantly inhibited osteoclastogenesis in healthy individuals but not in patients with RA and that the effect was mediated by NKT cells. Mice treated with the glycolipid showed less severe arthritis and reduced bone destruction.

“Further studies are needed to investigate ways of repairing NKT cell dysfunction in RA,” the investigators proposed.

Targeting natural killer T cells might help prevent bone destruction in rheumatoid arthritis, the results of a preclinical study suggest.

Natural killer T (NKT) cells stimulated by the glycolipid alpha-galactosylceramide (alphaGalCer) were found to have a regulatory effect on the development of osteoclasts, a type of bone cell that resorbs bone and is integral to bone repair and maintenance. These cells could have a protective effect on inflammatory bone destruction, the research team suggested after also finding that the cells’ effects were diminished in patients with RA versus healthy controls.

Hye-Mi Jin of the department of rheumatology at Chonnam National University Medical School and Hospital in Gwangju, South Korea, and associates isolated and cultured NKT cells from 25 subjects with and 15 without RA and performed in vitro experiments to investigate the role played by NKT cells in osteoclastogenesis. They also looked at the in vivo effects of the alphaGalCer-stimulated cells in a mouse model of collagen-induced arthritis (Arthritis Rheumatol. 2015 June 19 [doi:10.1002/art.39244]).

The in vitro studies showed that alphaGalCer significantly inhibited osteoclastogenesis in healthy individuals but not in patients with RA and that the effect was mediated by NKT cells. Mice treated with the glycolipid showed less severe arthritis and reduced bone destruction.

“Further studies are needed to investigate ways of repairing NKT cell dysfunction in RA,” the investigators proposed.

Targeting natural killer T cells might help prevent bone destruction in rheumatoid arthritis, the results of a preclinical study suggest.

Natural killer T (NKT) cells stimulated by the glycolipid alpha-galactosylceramide (alphaGalCer) were found to have a regulatory effect on the development of osteoclasts, a type of bone cell that resorbs bone and is integral to bone repair and maintenance. These cells could have a protective effect on inflammatory bone destruction, the research team suggested after also finding that the cells’ effects were diminished in patients with RA versus healthy controls.

Hye-Mi Jin of the department of rheumatology at Chonnam National University Medical School and Hospital in Gwangju, South Korea, and associates isolated and cultured NKT cells from 25 subjects with and 15 without RA and performed in vitro experiments to investigate the role played by NKT cells in osteoclastogenesis. They also looked at the in vivo effects of the alphaGalCer-stimulated cells in a mouse model of collagen-induced arthritis (Arthritis Rheumatol. 2015 June 19 [doi:10.1002/art.39244]).

The in vitro studies showed that alphaGalCer significantly inhibited osteoclastogenesis in healthy individuals but not in patients with RA and that the effect was mediated by NKT cells. Mice treated with the glycolipid showed less severe arthritis and reduced bone destruction.

“Further studies are needed to investigate ways of repairing NKT cell dysfunction in RA,” the investigators proposed.

The final results of a 2-year, phase III study assessing the clinical efficacy and safety of ustekinumab in 615 patients with active psoriatic arthritis confirm that joint- and skin-related improvements are maintained.

Data from the randomized, double blind, placebo-controlled PSUMMIT 1 study showed that 56.7%-63.6% of psoriatic arthritis (PsA) patients treated with a 45-mg or 90-mg dose every 12 weeks achieved American College of Rheumatology criteria for a 20% improvement in joint symptoms (ACR20). ACR50 and ACR70 responses ranged from 37.3% to 46% and 18.6% to 24.7%, respectively.

“The proportions of patients with either DAS28-CRP [28-joint Disease Activity Score using C-reactive protein] response or remission were maintained from week 52 to week 100,” noted lead study author Dr. Arthur Kavanaugh of the University of California-San Diego in La Jolla and his associates (Arthritis Care Res. 2015 June 19 [doi:10.1002/acr.22645]).

A moderate or good response according to DAS28-CRP was achieved by 71.9%-76.7% of patients. A 75% improvement in the Psoriasis Area and Severity Index (PASI) was achieved by 63.9%-72.5% of patients, and 41%-51.9% achieved a PASI 90. Mean changes in radiographic damage also were maintained.

“No unexpected safety events were observed through 2 years, and results were consistent with the known safety profile of ustekinumab,” Dr. Kavanaugh and his colleagues wrote, adding that the study “demonstrated a favorable benefit-risk profile of ustekinumab treatment in patients with active PsA.”

The trial was funded by Janssen Research & Development. Dr. Kavanaugh has received research support from AbbVie, Janssen, and UCB. Many of the other authors also had financial ties to Janssen and other manufacturers of biologics for psoriatic arthritis.

The final results of a 2-year, phase III study assessing the clinical efficacy and safety of ustekinumab in 615 patients with active psoriatic arthritis confirm that joint- and skin-related improvements are maintained.

Data from the randomized, double blind, placebo-controlled PSUMMIT 1 study showed that 56.7%-63.6% of psoriatic arthritis (PsA) patients treated with a 45-mg or 90-mg dose every 12 weeks achieved American College of Rheumatology criteria for a 20% improvement in joint symptoms (ACR20). ACR50 and ACR70 responses ranged from 37.3% to 46% and 18.6% to 24.7%, respectively.

“The proportions of patients with either DAS28-CRP [28-joint Disease Activity Score using C-reactive protein] response or remission were maintained from week 52 to week 100,” noted lead study author Dr. Arthur Kavanaugh of the University of California-San Diego in La Jolla and his associates (Arthritis Care Res. 2015 June 19 [doi:10.1002/acr.22645]).

A moderate or good response according to DAS28-CRP was achieved by 71.9%-76.7% of patients. A 75% improvement in the Psoriasis Area and Severity Index (PASI) was achieved by 63.9%-72.5% of patients, and 41%-51.9% achieved a PASI 90. Mean changes in radiographic damage also were maintained.

“No unexpected safety events were observed through 2 years, and results were consistent with the known safety profile of ustekinumab,” Dr. Kavanaugh and his colleagues wrote, adding that the study “demonstrated a favorable benefit-risk profile of ustekinumab treatment in patients with active PsA.”

The trial was funded by Janssen Research & Development. Dr. Kavanaugh has received research support from AbbVie, Janssen, and UCB. Many of the other authors also had financial ties to Janssen and other manufacturers of biologics for psoriatic arthritis.

The final results of a 2-year, phase III study assessing the clinical efficacy and safety of ustekinumab in 615 patients with active psoriatic arthritis confirm that joint- and skin-related improvements are maintained.

Data from the randomized, double blind, placebo-controlled PSUMMIT 1 study showed that 56.7%-63.6% of psoriatic arthritis (PsA) patients treated with a 45-mg or 90-mg dose every 12 weeks achieved American College of Rheumatology criteria for a 20% improvement in joint symptoms (ACR20). ACR50 and ACR70 responses ranged from 37.3% to 46% and 18.6% to 24.7%, respectively.

“The proportions of patients with either DAS28-CRP [28-joint Disease Activity Score using C-reactive protein] response or remission were maintained from week 52 to week 100,” noted lead study author Dr. Arthur Kavanaugh of the University of California-San Diego in La Jolla and his associates (Arthritis Care Res. 2015 June 19 [doi:10.1002/acr.22645]).

A moderate or good response according to DAS28-CRP was achieved by 71.9%-76.7% of patients. A 75% improvement in the Psoriasis Area and Severity Index (PASI) was achieved by 63.9%-72.5% of patients, and 41%-51.9% achieved a PASI 90. Mean changes in radiographic damage also were maintained.

“No unexpected safety events were observed through 2 years, and results were consistent with the known safety profile of ustekinumab,” Dr. Kavanaugh and his colleagues wrote, adding that the study “demonstrated a favorable benefit-risk profile of ustekinumab treatment in patients with active PsA.”

The trial was funded by Janssen Research & Development. Dr. Kavanaugh has received research support from AbbVie, Janssen, and UCB. Many of the other authors also had financial ties to Janssen and other manufacturers of biologics for psoriatic arthritis.

ROME – Patients with psoriasis were more likely to develop psoriatic arthritis if they had experienced physical trauma, based on data from a large, population-based study.

The crude incidence of psoriatic arthritis was 30 per 10,000 person-years in psoriasis patients exposed to trauma, compared with 22 per 10,000 person years in those who were not.

The hazard ratio (HR) for increased psoriatic arthritis risk with any trauma was 1.32 after adjusting for multiple factors, including patient age, gender, and the duration of psoriasis, senior study author Dr. Thorvardur Love said during a press briefing at the European Congress of Rheumatology.

“Patients with psoriasis are an easily identifiable group [to study] as they have skin disease on their body,” he noted. They also have a high risk of developing arthritis, at around 10%-30% of patients. This makes them an ideal population to study to try to find factors that might mitigate the risk and potentially have a large impact in clinical practice.

“The idea that trauma precipitates psoriatic arthritis is not new,” observed Dr. Love of Landspitali University Hospital in Reykjavik, Iceland. “It comes a little bit from the Koebner phenomenon, which is when psoriasis patients develop a new lesion in the skin where an injury has been.”

A few small studies had given rise to the idea that trauma could perhaps trigger a deep Koebner phenomenon in patients with psoriasis, and so the aim of the present analysis was to look at this idea in a larger population. Electronic health records of more than 10 million individuals living in the United Kingdom between 1995 and 2013 were analyzed from the Health Improvement Network (THIN) database. Of 70,646 patients with psoriasis who were identified, 15,416 had been exposed to some form of trauma, which was stratified as trauma involving the joints, bones, nerves, or skin.

After 425,120 person-years of follow-up, 1,010 incident cases of psoriatic arthritis had been recorded.

Having bone or joint trauma was found to increase the risk for psoriatic arthritis by 46% (HR, 1.46; 95% confidence interval, 1.13-1.54) and 50% (HR, 1.50; 95% CI. 1.19-1.90), respectively. This was after adjusting for age, gender, date of entry into the THIN database, duration of psoriasis, body mass index, smoking, alcohol consumption, and the number of visits to the general practitioner.

Neither nerve nor skin trauma were associated with an increased risk for psoriatic arthritis. Dr. Love and his fellow researchers also looked to see if patients with psoriasis had an increased risk of rheumatoid arthritis but found no significant association (HR, 1.04; 95% 0.99-1.10).

“The conclusion is that physical trauma is a risk factor for psoriatic arthritis among patients with psoriasis,” Dr. Love said. “We believe this is very important as the baseline risk is so high.”The effect is specific to psoriatic arthritis, as it is not seen in rheumatoid arthritis, which might provide clues for further research, he added. Why trauma might up the risk for developing psoriatic but not other types of inflammatory arthritis remains unclear, but the hypothesis is that patients would need to have a genetic predisposition and the “right types” of T cells in and around the joint that get disturbed in some way, perhaps by infection or by trauma. “I think it’s important to note that at this point we are not making any recommendations to the psoriasis community,” Dr. Love said. He suggested that, before any recommendations could be made, there needed to be a “really robust” conversation between patients, researchers, and physicians to determine exactly what these findings might mean. Certainly more research is needed before suggesting any lifestyle modifications that might help avoid situations associated with certain types of trauma, he said.

A literature review in the journal Clinical Rheumatology provided additional explanation of the deep Koebner effect. The investigators noted in their abstract that “the role of neuropeptides such as substance P and vasoactive intestinal peptide has been highlighted in the synovium after trauma.”

An editorial in the Journal of Rheumatology also suggested areas for additional research. Dr. Ignazio Olivieri of San Carlo Hospital in Potenza, Italy, wrote that “criteria of imputability” that should be met include “single and significant trauma; absence of joint lesion before trauma; localization of arthritis in the area of trauma; and absence or short delay between trauma and onset of arthritis.”

“You might envision treating [psoriasis] patients early [for psoriatic arthritis] if they break a leg or get a joint dislocation, but we are not there yet,” Dr. Love stressed. “This is an idea of where we could take this and where we might actually be able to have an effect.”

The research was performed by researchers at the University of Iceland (Reykjavik) in collaboration with researchers at Harvard Medical School in Boston and the University of Pennsylvania in Philadelphia. It was partially funded by the Icelandic Centre for Research (RANNIS) and the National Institutes of Health. Dr. Love’s associate, Dr. Stefan Thorarensen of the division of public health at the University of Iceland, presented the findings during the clinical science session at the congress.

Dr. Love and his coauthors reported having no financial disclosures.

ROME – Patients with psoriasis were more likely to develop psoriatic arthritis if they had experienced physical trauma, based on data from a large, population-based study.

The crude incidence of psoriatic arthritis was 30 per 10,000 person-years in psoriasis patients exposed to trauma, compared with 22 per 10,000 person years in those who were not.

The hazard ratio (HR) for increased psoriatic arthritis risk with any trauma was 1.32 after adjusting for multiple factors, including patient age, gender, and the duration of psoriasis, senior study author Dr. Thorvardur Love said during a press briefing at the European Congress of Rheumatology.

“Patients with psoriasis are an easily identifiable group [to study] as they have skin disease on their body,” he noted. They also have a high risk of developing arthritis, at around 10%-30% of patients. This makes them an ideal population to study to try to find factors that might mitigate the risk and potentially have a large impact in clinical practice.

“The idea that trauma precipitates psoriatic arthritis is not new,” observed Dr. Love of Landspitali University Hospital in Reykjavik, Iceland. “It comes a little bit from the Koebner phenomenon, which is when psoriasis patients develop a new lesion in the skin where an injury has been.”

A few small studies had given rise to the idea that trauma could perhaps trigger a deep Koebner phenomenon in patients with psoriasis, and so the aim of the present analysis was to look at this idea in a larger population. Electronic health records of more than 10 million individuals living in the United Kingdom between 1995 and 2013 were analyzed from the Health Improvement Network (THIN) database. Of 70,646 patients with psoriasis who were identified, 15,416 had been exposed to some form of trauma, which was stratified as trauma involving the joints, bones, nerves, or skin.

After 425,120 person-years of follow-up, 1,010 incident cases of psoriatic arthritis had been recorded.

Having bone or joint trauma was found to increase the risk for psoriatic arthritis by 46% (HR, 1.46; 95% confidence interval, 1.13-1.54) and 50% (HR, 1.50; 95% CI. 1.19-1.90), respectively. This was after adjusting for age, gender, date of entry into the THIN database, duration of psoriasis, body mass index, smoking, alcohol consumption, and the number of visits to the general practitioner.

Neither nerve nor skin trauma were associated with an increased risk for psoriatic arthritis. Dr. Love and his fellow researchers also looked to see if patients with psoriasis had an increased risk of rheumatoid arthritis but found no significant association (HR, 1.04; 95% 0.99-1.10).

“The conclusion is that physical trauma is a risk factor for psoriatic arthritis among patients with psoriasis,” Dr. Love said. “We believe this is very important as the baseline risk is so high.”The effect is specific to psoriatic arthritis, as it is not seen in rheumatoid arthritis, which might provide clues for further research, he added. Why trauma might up the risk for developing psoriatic but not other types of inflammatory arthritis remains unclear, but the hypothesis is that patients would need to have a genetic predisposition and the “right types” of T cells in and around the joint that get disturbed in some way, perhaps by infection or by trauma. “I think it’s important to note that at this point we are not making any recommendations to the psoriasis community,” Dr. Love said. He suggested that, before any recommendations could be made, there needed to be a “really robust” conversation between patients, researchers, and physicians to determine exactly what these findings might mean. Certainly more research is needed before suggesting any lifestyle modifications that might help avoid situations associated with certain types of trauma, he said.

A literature review in the journal Clinical Rheumatology provided additional explanation of the deep Koebner effect. The investigators noted in their abstract that “the role of neuropeptides such as substance P and vasoactive intestinal peptide has been highlighted in the synovium after trauma.”

An editorial in the Journal of Rheumatology also suggested areas for additional research. Dr. Ignazio Olivieri of San Carlo Hospital in Potenza, Italy, wrote that “criteria of imputability” that should be met include “single and significant trauma; absence of joint lesion before trauma; localization of arthritis in the area of trauma; and absence or short delay between trauma and onset of arthritis.”

“You might envision treating [psoriasis] patients early [for psoriatic arthritis] if they break a leg or get a joint dislocation, but we are not there yet,” Dr. Love stressed. “This is an idea of where we could take this and where we might actually be able to have an effect.”

The research was performed by researchers at the University of Iceland (Reykjavik) in collaboration with researchers at Harvard Medical School in Boston and the University of Pennsylvania in Philadelphia. It was partially funded by the Icelandic Centre for Research (RANNIS) and the National Institutes of Health. Dr. Love’s associate, Dr. Stefan Thorarensen of the division of public health at the University of Iceland, presented the findings during the clinical science session at the congress.

Dr. Love and his coauthors reported having no financial disclosures.

ROME – Patients with psoriasis were more likely to develop psoriatic arthritis if they had experienced physical trauma, based on data from a large, population-based study.

The crude incidence of psoriatic arthritis was 30 per 10,000 person-years in psoriasis patients exposed to trauma, compared with 22 per 10,000 person years in those who were not.

The hazard ratio (HR) for increased psoriatic arthritis risk with any trauma was 1.32 after adjusting for multiple factors, including patient age, gender, and the duration of psoriasis, senior study author Dr. Thorvardur Love said during a press briefing at the European Congress of Rheumatology.

“Patients with psoriasis are an easily identifiable group [to study] as they have skin disease on their body,” he noted. They also have a high risk of developing arthritis, at around 10%-30% of patients. This makes them an ideal population to study to try to find factors that might mitigate the risk and potentially have a large impact in clinical practice.

“The idea that trauma precipitates psoriatic arthritis is not new,” observed Dr. Love of Landspitali University Hospital in Reykjavik, Iceland. “It comes a little bit from the Koebner phenomenon, which is when psoriasis patients develop a new lesion in the skin where an injury has been.”

A few small studies had given rise to the idea that trauma could perhaps trigger a deep Koebner phenomenon in patients with psoriasis, and so the aim of the present analysis was to look at this idea in a larger population. Electronic health records of more than 10 million individuals living in the United Kingdom between 1995 and 2013 were analyzed from the Health Improvement Network (THIN) database. Of 70,646 patients with psoriasis who were identified, 15,416 had been exposed to some form of trauma, which was stratified as trauma involving the joints, bones, nerves, or skin.

After 425,120 person-years of follow-up, 1,010 incident cases of psoriatic arthritis had been recorded.

Having bone or joint trauma was found to increase the risk for psoriatic arthritis by 46% (HR, 1.46; 95% confidence interval, 1.13-1.54) and 50% (HR, 1.50; 95% CI. 1.19-1.90), respectively. This was after adjusting for age, gender, date of entry into the THIN database, duration of psoriasis, body mass index, smoking, alcohol consumption, and the number of visits to the general practitioner.

Neither nerve nor skin trauma were associated with an increased risk for psoriatic arthritis. Dr. Love and his fellow researchers also looked to see if patients with psoriasis had an increased risk of rheumatoid arthritis but found no significant association (HR, 1.04; 95% 0.99-1.10).

“The conclusion is that physical trauma is a risk factor for psoriatic arthritis among patients with psoriasis,” Dr. Love said. “We believe this is very important as the baseline risk is so high.”The effect is specific to psoriatic arthritis, as it is not seen in rheumatoid arthritis, which might provide clues for further research, he added. Why trauma might up the risk for developing psoriatic but not other types of inflammatory arthritis remains unclear, but the hypothesis is that patients would need to have a genetic predisposition and the “right types” of T cells in and around the joint that get disturbed in some way, perhaps by infection or by trauma. “I think it’s important to note that at this point we are not making any recommendations to the psoriasis community,” Dr. Love said. He suggested that, before any recommendations could be made, there needed to be a “really robust” conversation between patients, researchers, and physicians to determine exactly what these findings might mean. Certainly more research is needed before suggesting any lifestyle modifications that might help avoid situations associated with certain types of trauma, he said.

A literature review in the journal Clinical Rheumatology provided additional explanation of the deep Koebner effect. The investigators noted in their abstract that “the role of neuropeptides such as substance P and vasoactive intestinal peptide has been highlighted in the synovium after trauma.”

An editorial in the Journal of Rheumatology also suggested areas for additional research. Dr. Ignazio Olivieri of San Carlo Hospital in Potenza, Italy, wrote that “criteria of imputability” that should be met include “single and significant trauma; absence of joint lesion before trauma; localization of arthritis in the area of trauma; and absence or short delay between trauma and onset of arthritis.”

“You might envision treating [psoriasis] patients early [for psoriatic arthritis] if they break a leg or get a joint dislocation, but we are not there yet,” Dr. Love stressed. “This is an idea of where we could take this and where we might actually be able to have an effect.”

The research was performed by researchers at the University of Iceland (Reykjavik) in collaboration with researchers at Harvard Medical School in Boston and the University of Pennsylvania in Philadelphia. It was partially funded by the Icelandic Centre for Research (RANNIS) and the National Institutes of Health. Dr. Love’s associate, Dr. Stefan Thorarensen of the division of public health at the University of Iceland, presented the findings during the clinical science session at the congress.

Dr. Love and his coauthors reported having no financial disclosures.