User login
Study finds predictors of progression to Sjögren’s syndrome
Elevated serum gamma globulin or low complement levels in patients with symptoms of Sjögren’s syndrome (SS) may predict their likelihood of progression to the autoimmune disease, according to findings from a longitudinal cohort study.
“Identification of serological variables that predict the development of Sjögren’s syndrome may contribute to earlier diagnosis and treatment of the disease and, ultimately, better long-term outcome,” Caroline H. Shiboski, DDS, PhD, chair of the department of orofacial sciences at the University of California, San Francisco, and her coauthors wrote.
The researchers described the results of a follow-up visit 2 years after baseline for 771 of 3,310 participants in the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry.
Approximately half of the participants did not meet either the 2012 American College of Rheumatology criteria or the 2016 ACR-European League Against Rheumatism criteria for Sjögren’s syndrome at baseline. At follow-up, 8% met the ACR criteria, and 9% met the ACR-EULAR criteria (Arthritis Care Res. 2017 April 24. doi: 10.1002/acr.23264).
For the other patients, those who did not progress according to either criteria, the researchers “observed remarkable stability over 2-3 years for both individual phenotypic features of SS and SS status, a finding consistent with smaller prospective studies with longer durations of follow-up.”
The participants with hypergammaglobulinemia at study entry, defined as immunoglobulin G greater than 1,445 mg/dL, were four times more likely to progress to full disease after 2 years (P = .006), while those with hypocomplementemia were six times more likely to progress (P = .004) than were those without. Hypocomplementemia was defined as C3 less than 90 mg/dL and/or C4 less than 16 mg/dL.
“However, the highest percentage of progression from not meeting the SS criteria at baseline to meeting them at the 2- to 3-year follow-up was among those who reported receiving immunomodulating/suppressive medications at both time points, both when using the ACR criteria (18% progressors) and the ACR-EULAR criteria (12% progressors),” the authors wrote.
In general, those with confirmed diagnosis at study entry showed reasonable stability in both individual phenotypic features and disease status.
Overall, 93% of participants who met the ACR criteria for SS at baseline still met those criteria at the 2- to 3-year follow-up, as did 89% of participants who met the ACR-EULAR criteria at baseline.
A majority of the participants who reverted from SS classification at baseline to failure to meet the criteria at follow-up had a change in labial salivary gland biopsy results. This occurred in 60% who met ACR criteria at baseline and 75% who met ACR-EULAR criteria at baseline.
More than 85% of participants in the study reported dry mouth or dry eyes, but participants with SS were much more likely to have positive anti-SSA, positive rheumatoid factor, antinuclear antibody titer of 1:320 or greater, hypergammaglobulinemia, and focal lymphocytic sialadenitis with a focus score of 1 or more focus per 4 mm2.
The researchers also reported a very low incidence (0.5%) of lymphoma among the participants available for follow-up.
The study was supported by the National Institutes of Health, the Jerome L. Greene Foundation, and the Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center. Six authors declared consultancies, honoraria, and grants from pharmaceutical companies.
Elevated serum gamma globulin or low complement levels in patients with symptoms of Sjögren’s syndrome (SS) may predict their likelihood of progression to the autoimmune disease, according to findings from a longitudinal cohort study.
“Identification of serological variables that predict the development of Sjögren’s syndrome may contribute to earlier diagnosis and treatment of the disease and, ultimately, better long-term outcome,” Caroline H. Shiboski, DDS, PhD, chair of the department of orofacial sciences at the University of California, San Francisco, and her coauthors wrote.
The researchers described the results of a follow-up visit 2 years after baseline for 771 of 3,310 participants in the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry.
Approximately half of the participants did not meet either the 2012 American College of Rheumatology criteria or the 2016 ACR-European League Against Rheumatism criteria for Sjögren’s syndrome at baseline. At follow-up, 8% met the ACR criteria, and 9% met the ACR-EULAR criteria (Arthritis Care Res. 2017 April 24. doi: 10.1002/acr.23264).
For the other patients, those who did not progress according to either criteria, the researchers “observed remarkable stability over 2-3 years for both individual phenotypic features of SS and SS status, a finding consistent with smaller prospective studies with longer durations of follow-up.”
The participants with hypergammaglobulinemia at study entry, defined as immunoglobulin G greater than 1,445 mg/dL, were four times more likely to progress to full disease after 2 years (P = .006), while those with hypocomplementemia were six times more likely to progress (P = .004) than were those without. Hypocomplementemia was defined as C3 less than 90 mg/dL and/or C4 less than 16 mg/dL.
“However, the highest percentage of progression from not meeting the SS criteria at baseline to meeting them at the 2- to 3-year follow-up was among those who reported receiving immunomodulating/suppressive medications at both time points, both when using the ACR criteria (18% progressors) and the ACR-EULAR criteria (12% progressors),” the authors wrote.
In general, those with confirmed diagnosis at study entry showed reasonable stability in both individual phenotypic features and disease status.
Overall, 93% of participants who met the ACR criteria for SS at baseline still met those criteria at the 2- to 3-year follow-up, as did 89% of participants who met the ACR-EULAR criteria at baseline.
A majority of the participants who reverted from SS classification at baseline to failure to meet the criteria at follow-up had a change in labial salivary gland biopsy results. This occurred in 60% who met ACR criteria at baseline and 75% who met ACR-EULAR criteria at baseline.
More than 85% of participants in the study reported dry mouth or dry eyes, but participants with SS were much more likely to have positive anti-SSA, positive rheumatoid factor, antinuclear antibody titer of 1:320 or greater, hypergammaglobulinemia, and focal lymphocytic sialadenitis with a focus score of 1 or more focus per 4 mm2.
The researchers also reported a very low incidence (0.5%) of lymphoma among the participants available for follow-up.
The study was supported by the National Institutes of Health, the Jerome L. Greene Foundation, and the Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center. Six authors declared consultancies, honoraria, and grants from pharmaceutical companies.
Elevated serum gamma globulin or low complement levels in patients with symptoms of Sjögren’s syndrome (SS) may predict their likelihood of progression to the autoimmune disease, according to findings from a longitudinal cohort study.
“Identification of serological variables that predict the development of Sjögren’s syndrome may contribute to earlier diagnosis and treatment of the disease and, ultimately, better long-term outcome,” Caroline H. Shiboski, DDS, PhD, chair of the department of orofacial sciences at the University of California, San Francisco, and her coauthors wrote.
The researchers described the results of a follow-up visit 2 years after baseline for 771 of 3,310 participants in the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry.
Approximately half of the participants did not meet either the 2012 American College of Rheumatology criteria or the 2016 ACR-European League Against Rheumatism criteria for Sjögren’s syndrome at baseline. At follow-up, 8% met the ACR criteria, and 9% met the ACR-EULAR criteria (Arthritis Care Res. 2017 April 24. doi: 10.1002/acr.23264).
For the other patients, those who did not progress according to either criteria, the researchers “observed remarkable stability over 2-3 years for both individual phenotypic features of SS and SS status, a finding consistent with smaller prospective studies with longer durations of follow-up.”
The participants with hypergammaglobulinemia at study entry, defined as immunoglobulin G greater than 1,445 mg/dL, were four times more likely to progress to full disease after 2 years (P = .006), while those with hypocomplementemia were six times more likely to progress (P = .004) than were those without. Hypocomplementemia was defined as C3 less than 90 mg/dL and/or C4 less than 16 mg/dL.
“However, the highest percentage of progression from not meeting the SS criteria at baseline to meeting them at the 2- to 3-year follow-up was among those who reported receiving immunomodulating/suppressive medications at both time points, both when using the ACR criteria (18% progressors) and the ACR-EULAR criteria (12% progressors),” the authors wrote.
In general, those with confirmed diagnosis at study entry showed reasonable stability in both individual phenotypic features and disease status.
Overall, 93% of participants who met the ACR criteria for SS at baseline still met those criteria at the 2- to 3-year follow-up, as did 89% of participants who met the ACR-EULAR criteria at baseline.
A majority of the participants who reverted from SS classification at baseline to failure to meet the criteria at follow-up had a change in labial salivary gland biopsy results. This occurred in 60% who met ACR criteria at baseline and 75% who met ACR-EULAR criteria at baseline.
More than 85% of participants in the study reported dry mouth or dry eyes, but participants with SS were much more likely to have positive anti-SSA, positive rheumatoid factor, antinuclear antibody titer of 1:320 or greater, hypergammaglobulinemia, and focal lymphocytic sialadenitis with a focus score of 1 or more focus per 4 mm2.
The researchers also reported a very low incidence (0.5%) of lymphoma among the participants available for follow-up.
The study was supported by the National Institutes of Health, the Jerome L. Greene Foundation, and the Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center. Six authors declared consultancies, honoraria, and grants from pharmaceutical companies.
Key clinical point:
Major finding: Patients with symptoms of Sjögren’s syndrome and hypergammaglobulinemia are four times more likely to progress to full disease than are those without.
Data source: A longitudinal cohort study of 3,310 participants in the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry.
Disclosures: The study was supported by the National Institutes of Health, the Jerome L. Greene Foundation, and the Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center. Six authors declared consultancies, honoraria, and grants from pharmaceutical companies.
Mortality rate was 10-fold higher in opioid use disorder patients
Individuals with opioid use disorder had a 10-fold higher mortality rate than the general population in a general health care setting, according to a study of 2,576 patients.
When researchers examined the electronic health records of opioid use disorder patients in a large university health system and linked those with mortality data, they found those patients had a standardized mortality ratio of 10.3, compared with the general population and adjusted for sex and age (J Addict Med. 2017 Apr 20. doi: 10.1097/ADM.0000000000000312).
Hepatitis C infection and alcohol use disorder were the two mostly clinically important indicators of overall mortality risk; however, none of the factors examined was a predictor of drug-related deaths.
Patients who died were also more likely to have been diagnosed with other substance use disorders, such as tobacco, alcohol, cannabis, or cocaine, and to have comorbidities such as heart disease, respiratory disease, hepatitis C infection, liver disease, cancer, or diabetes. The most common cause of death was drug-related – including poisoning, overdose, and alcohol and drug disorder – followed by cardiovascular disease, cancer, and infectious diseases such as hepatitis C.
Yih-Ing Hser, PhD, of the University of California, Los Angeles, and her coauthors called the elevated mortality rates in that group “alarming,” and suggested the rates may be the result of issues that health care systems have in identifying and addressing opioid use disorder problems.
“First, SUDs [substance use disorders] are not routinely screened for in primary care, and most primary care physicians have not received adequate training to diagnose and treat OUD [opioid use disorder],” the authors wrote. “It is likely that patients seen in this health system became progressively sicker, as their OUD problem was not identified until very late in its course and after physical health complications had already ensued.”
Second, patients with opioid use disorder may not be getting referrals for treatment. Finally, those who have problems with prescription opioids may be harder to identify than patients with heroin addiction.
“The alarmingly high morbidity and mortality among OUD patients revealed in the present study challenge health care systems to find new and innovative ways to expand evidence-based strategies for OUD in a variety of settings,” the investigators concluded.
The study was partly supported by the National Institute on Drug Abuse and the National Center for Advancing Translational Science. One author declared royalties as a section editor for UpToDate. No other conflicts of interest were declared.
Everyone is trying to respond to the opioid abuse and overdose crisis with the tools available. However, while medication-assisted therapies have been used successfully by addiction medicine and addiction psychiatry experts and programs as part of an overall program of recovery, their use as stand-alone substitution treatments has expanded.
These new data, like other recent data on emergency department interventions, strongly suggest that these treatments are limited in efficacy, and longer-term outcome studies, typical in medical oncology and physician addiction, are needed.
Dr. Mark Gold is adjunct professor of psychiatry at Washington University in St. Louis, and former Donald R. Dizney Eminent Scholar and chairman of the psychiatry department at the University of Florida, Gainesville.
Everyone is trying to respond to the opioid abuse and overdose crisis with the tools available. However, while medication-assisted therapies have been used successfully by addiction medicine and addiction psychiatry experts and programs as part of an overall program of recovery, their use as stand-alone substitution treatments has expanded.
These new data, like other recent data on emergency department interventions, strongly suggest that these treatments are limited in efficacy, and longer-term outcome studies, typical in medical oncology and physician addiction, are needed.
Dr. Mark Gold is adjunct professor of psychiatry at Washington University in St. Louis, and former Donald R. Dizney Eminent Scholar and chairman of the psychiatry department at the University of Florida, Gainesville.
Everyone is trying to respond to the opioid abuse and overdose crisis with the tools available. However, while medication-assisted therapies have been used successfully by addiction medicine and addiction psychiatry experts and programs as part of an overall program of recovery, their use as stand-alone substitution treatments has expanded.
These new data, like other recent data on emergency department interventions, strongly suggest that these treatments are limited in efficacy, and longer-term outcome studies, typical in medical oncology and physician addiction, are needed.
Dr. Mark Gold is adjunct professor of psychiatry at Washington University in St. Louis, and former Donald R. Dizney Eminent Scholar and chairman of the psychiatry department at the University of Florida, Gainesville.
Individuals with opioid use disorder had a 10-fold higher mortality rate than the general population in a general health care setting, according to a study of 2,576 patients.
When researchers examined the electronic health records of opioid use disorder patients in a large university health system and linked those with mortality data, they found those patients had a standardized mortality ratio of 10.3, compared with the general population and adjusted for sex and age (J Addict Med. 2017 Apr 20. doi: 10.1097/ADM.0000000000000312).
Hepatitis C infection and alcohol use disorder were the two mostly clinically important indicators of overall mortality risk; however, none of the factors examined was a predictor of drug-related deaths.
Patients who died were also more likely to have been diagnosed with other substance use disorders, such as tobacco, alcohol, cannabis, or cocaine, and to have comorbidities such as heart disease, respiratory disease, hepatitis C infection, liver disease, cancer, or diabetes. The most common cause of death was drug-related – including poisoning, overdose, and alcohol and drug disorder – followed by cardiovascular disease, cancer, and infectious diseases such as hepatitis C.
Yih-Ing Hser, PhD, of the University of California, Los Angeles, and her coauthors called the elevated mortality rates in that group “alarming,” and suggested the rates may be the result of issues that health care systems have in identifying and addressing opioid use disorder problems.
“First, SUDs [substance use disorders] are not routinely screened for in primary care, and most primary care physicians have not received adequate training to diagnose and treat OUD [opioid use disorder],” the authors wrote. “It is likely that patients seen in this health system became progressively sicker, as their OUD problem was not identified until very late in its course and after physical health complications had already ensued.”
Second, patients with opioid use disorder may not be getting referrals for treatment. Finally, those who have problems with prescription opioids may be harder to identify than patients with heroin addiction.
“The alarmingly high morbidity and mortality among OUD patients revealed in the present study challenge health care systems to find new and innovative ways to expand evidence-based strategies for OUD in a variety of settings,” the investigators concluded.
The study was partly supported by the National Institute on Drug Abuse and the National Center for Advancing Translational Science. One author declared royalties as a section editor for UpToDate. No other conflicts of interest were declared.
Individuals with opioid use disorder had a 10-fold higher mortality rate than the general population in a general health care setting, according to a study of 2,576 patients.
When researchers examined the electronic health records of opioid use disorder patients in a large university health system and linked those with mortality data, they found those patients had a standardized mortality ratio of 10.3, compared with the general population and adjusted for sex and age (J Addict Med. 2017 Apr 20. doi: 10.1097/ADM.0000000000000312).
Hepatitis C infection and alcohol use disorder were the two mostly clinically important indicators of overall mortality risk; however, none of the factors examined was a predictor of drug-related deaths.
Patients who died were also more likely to have been diagnosed with other substance use disorders, such as tobacco, alcohol, cannabis, or cocaine, and to have comorbidities such as heart disease, respiratory disease, hepatitis C infection, liver disease, cancer, or diabetes. The most common cause of death was drug-related – including poisoning, overdose, and alcohol and drug disorder – followed by cardiovascular disease, cancer, and infectious diseases such as hepatitis C.
Yih-Ing Hser, PhD, of the University of California, Los Angeles, and her coauthors called the elevated mortality rates in that group “alarming,” and suggested the rates may be the result of issues that health care systems have in identifying and addressing opioid use disorder problems.
“First, SUDs [substance use disorders] are not routinely screened for in primary care, and most primary care physicians have not received adequate training to diagnose and treat OUD [opioid use disorder],” the authors wrote. “It is likely that patients seen in this health system became progressively sicker, as their OUD problem was not identified until very late in its course and after physical health complications had already ensued.”
Second, patients with opioid use disorder may not be getting referrals for treatment. Finally, those who have problems with prescription opioids may be harder to identify than patients with heroin addiction.
“The alarmingly high morbidity and mortality among OUD patients revealed in the present study challenge health care systems to find new and innovative ways to expand evidence-based strategies for OUD in a variety of settings,” the investigators concluded.
The study was partly supported by the National Institute on Drug Abuse and the National Center for Advancing Translational Science. One author declared royalties as a section editor for UpToDate. No other conflicts of interest were declared.
Key clinical point: Individuals with opioid use disorder have a significantly higher mortality rate than the general population, particularly those with hepatitis C infection or alcohol use disorder.
Major finding: Patients with opioid use disorder had a standardized mortality ratio of 10.3, compared with the general population.
Data source: A cohort study in 2,576 opioid use disorder patients.
Disclosures: The study was partly supported by the National Institute on Drug Abuse and the National Center for Advancing Translational Science. One author declared royalties as a section editor for UpToDate. No other conflicts of interest were declared.
RA treatment delays raise risk of long-term disability
Initiating disease-modifying antirheumatic drugs within 6 months of a diagnosis of rheumatoid arthritis is associated with significantly lower disability scores over the long term, new research suggests.
Better diagnosis and access to early treatment has also likely played a role in a global decline in mortality from rheumatoid arthritis over a recent 25-year period, according to an analysis of World Health Organization and United Nations data, but the decline has occurred unequally across countries.
Impact of early treatment on disability
In the first of two separate studies published online April 20 in Arthritis & Rheumatology, U.K. researchers followed 602 patients from the Norfolk Arthritis Register for 20 years, starting in 1990-1994, and collected clinical data at baseline and years 1-3, 5, 7, 10, 15, and 20.
However, patients who began treatment within 6 months of diagnosis had disability scores similar to those of patients who were never initiated on treatment (Arthritis Rheumatol. 2017 April 20. doi: 10.1002/art.40090).
“This supports the importance of the “window of opportunity” construct for treatment, showing that early treatment leads to improved outcomes even into the second decade following symptom onset,” wrote first author James M. Gwinnutt, a PhD candidate at the University of Manchester (England), and his coauthors. “Increased functional disability over time could be due to worse joint damage, and it has been shown that those who receive later treatment have higher radiological scores at follow-up than those treated early.”
There were 88 deaths in the early treatment group (55%) during the follow-up period, 99 deaths (39.8%) in the late treatment group, and 78 deaths (40.4%) in the never-treated group.
When the researchers adjusted for disease severity in a comparison of mortality across the groups, they found a trend toward a reduced risk of mortality in patients treated early, compared with those who began treatment later, although this did not reach statistical significance.
However, patients in both the early treatment and late treatment groups showed significantly elevated standardized mortality rates, compared with the general population of Norfolk, while the never-treated group showed slightly – but not significantly – elevated mortality.
Overall, around one-quarter of patients (26.6%) began treatment within 6 months of the onset of symptoms, 19.9% were started on treatment within 6-12 months, 17.4% started within 1-2 years, 19% did not start treatment until more than 2 years after symptom onset, and 43.7% of the cohort never received treatment but still attended follow-up.
Patients who began earlier treatment had worse clinical characteristics than did those who began treatment later, except for tender joint counts and autoantibody status.
Researchers saw an overall decline in median swollen joint count and tender joint count in the first year after baseline, and this remained low throughout the course of the study.
Median Health Assessment Questionnaire scores also fell after baseline but then increased steadily from year 2 to year 20, exceeding baseline levels by year 7.
“This paper has two important messages, firstly about the long-term outcome of patients with RA in the modern era treated according to best practice at the time of presentation; secondly about the benefit of early treatment which is still apparent into the second decade after symptom onset with respect to functional disability,” the authors wrote.
An uneven global decline in mortality from RA
Meanwhile, a second study showed that mortality from rheumatoid arthritis declined globally across 31 countries from 1987 to 2011, according to data from the World Health Organization mortality database and the United Nations.
The absolute number of deaths where rheumatoid arthritis was registered as the underlying cause of death declined from 0.12% of all-cause deaths in 1987 to 0.09% of all-cause deaths in 2011 (Arthritis Rheumatol. 2017 April 20. doi: 10.1002/art.40091).
The mean age-standardized mortality rate declined by 48.2%, from 7.1 per million person-years in 1987-1989 to 3.7 in 2009-2011.
However, there was considerable variation between countries; the greatest reduction was seen in Finland, which had an absolute reduction of 20.6 fewer deaths per million person-years, while Croatia had an increase of 3.7 deaths per million person-years.
Younger people with rheumatoid arthritis showed the greatest reductions in mortality, while those in older age groups had smaller reductions in mortality.
“It has been suggested that changes in the management of RA toward early and aggressive treatment with disease-modifying antirheumatic drugs and subsequent biologic therapies has led to better health status and lower mortality for most people with RA over time,” wrote first author Aliasghar A. Kiadaliri, PhD, of Lund (Sweden) University, and his coauthors.
“These findings alongside aging of the population and fall in mortality may lead to an increase in the number of people with RA. Given that it appears that people with RA are now living longer, increase in burden of RA on health care systems is expected and policy makers should be made aware about to appropriately plan for this anticipated increase.”
The first study was supported by Arthritis Research UK. The second study was supported by the Swedish Research Council, Crafoord Foundation, Greta and Johan Kocks Foundation, the Faculty of Medicine Lund University, governmental funding of clinical research within Sweden’s National Health Service. No conflicts of interest were declared for either paper.
Initiating disease-modifying antirheumatic drugs within 6 months of a diagnosis of rheumatoid arthritis is associated with significantly lower disability scores over the long term, new research suggests.
Better diagnosis and access to early treatment has also likely played a role in a global decline in mortality from rheumatoid arthritis over a recent 25-year period, according to an analysis of World Health Organization and United Nations data, but the decline has occurred unequally across countries.
Impact of early treatment on disability
In the first of two separate studies published online April 20 in Arthritis & Rheumatology, U.K. researchers followed 602 patients from the Norfolk Arthritis Register for 20 years, starting in 1990-1994, and collected clinical data at baseline and years 1-3, 5, 7, 10, 15, and 20.
However, patients who began treatment within 6 months of diagnosis had disability scores similar to those of patients who were never initiated on treatment (Arthritis Rheumatol. 2017 April 20. doi: 10.1002/art.40090).
“This supports the importance of the “window of opportunity” construct for treatment, showing that early treatment leads to improved outcomes even into the second decade following symptom onset,” wrote first author James M. Gwinnutt, a PhD candidate at the University of Manchester (England), and his coauthors. “Increased functional disability over time could be due to worse joint damage, and it has been shown that those who receive later treatment have higher radiological scores at follow-up than those treated early.”
There were 88 deaths in the early treatment group (55%) during the follow-up period, 99 deaths (39.8%) in the late treatment group, and 78 deaths (40.4%) in the never-treated group.
When the researchers adjusted for disease severity in a comparison of mortality across the groups, they found a trend toward a reduced risk of mortality in patients treated early, compared with those who began treatment later, although this did not reach statistical significance.
However, patients in both the early treatment and late treatment groups showed significantly elevated standardized mortality rates, compared with the general population of Norfolk, while the never-treated group showed slightly – but not significantly – elevated mortality.
Overall, around one-quarter of patients (26.6%) began treatment within 6 months of the onset of symptoms, 19.9% were started on treatment within 6-12 months, 17.4% started within 1-2 years, 19% did not start treatment until more than 2 years after symptom onset, and 43.7% of the cohort never received treatment but still attended follow-up.
Patients who began earlier treatment had worse clinical characteristics than did those who began treatment later, except for tender joint counts and autoantibody status.
Researchers saw an overall decline in median swollen joint count and tender joint count in the first year after baseline, and this remained low throughout the course of the study.
Median Health Assessment Questionnaire scores also fell after baseline but then increased steadily from year 2 to year 20, exceeding baseline levels by year 7.
“This paper has two important messages, firstly about the long-term outcome of patients with RA in the modern era treated according to best practice at the time of presentation; secondly about the benefit of early treatment which is still apparent into the second decade after symptom onset with respect to functional disability,” the authors wrote.
An uneven global decline in mortality from RA
Meanwhile, a second study showed that mortality from rheumatoid arthritis declined globally across 31 countries from 1987 to 2011, according to data from the World Health Organization mortality database and the United Nations.
The absolute number of deaths where rheumatoid arthritis was registered as the underlying cause of death declined from 0.12% of all-cause deaths in 1987 to 0.09% of all-cause deaths in 2011 (Arthritis Rheumatol. 2017 April 20. doi: 10.1002/art.40091).
The mean age-standardized mortality rate declined by 48.2%, from 7.1 per million person-years in 1987-1989 to 3.7 in 2009-2011.
However, there was considerable variation between countries; the greatest reduction was seen in Finland, which had an absolute reduction of 20.6 fewer deaths per million person-years, while Croatia had an increase of 3.7 deaths per million person-years.
Younger people with rheumatoid arthritis showed the greatest reductions in mortality, while those in older age groups had smaller reductions in mortality.
“It has been suggested that changes in the management of RA toward early and aggressive treatment with disease-modifying antirheumatic drugs and subsequent biologic therapies has led to better health status and lower mortality for most people with RA over time,” wrote first author Aliasghar A. Kiadaliri, PhD, of Lund (Sweden) University, and his coauthors.
“These findings alongside aging of the population and fall in mortality may lead to an increase in the number of people with RA. Given that it appears that people with RA are now living longer, increase in burden of RA on health care systems is expected and policy makers should be made aware about to appropriately plan for this anticipated increase.”
The first study was supported by Arthritis Research UK. The second study was supported by the Swedish Research Council, Crafoord Foundation, Greta and Johan Kocks Foundation, the Faculty of Medicine Lund University, governmental funding of clinical research within Sweden’s National Health Service. No conflicts of interest were declared for either paper.
Initiating disease-modifying antirheumatic drugs within 6 months of a diagnosis of rheumatoid arthritis is associated with significantly lower disability scores over the long term, new research suggests.
Better diagnosis and access to early treatment has also likely played a role in a global decline in mortality from rheumatoid arthritis over a recent 25-year period, according to an analysis of World Health Organization and United Nations data, but the decline has occurred unequally across countries.
Impact of early treatment on disability
In the first of two separate studies published online April 20 in Arthritis & Rheumatology, U.K. researchers followed 602 patients from the Norfolk Arthritis Register for 20 years, starting in 1990-1994, and collected clinical data at baseline and years 1-3, 5, 7, 10, 15, and 20.
However, patients who began treatment within 6 months of diagnosis had disability scores similar to those of patients who were never initiated on treatment (Arthritis Rheumatol. 2017 April 20. doi: 10.1002/art.40090).
“This supports the importance of the “window of opportunity” construct for treatment, showing that early treatment leads to improved outcomes even into the second decade following symptom onset,” wrote first author James M. Gwinnutt, a PhD candidate at the University of Manchester (England), and his coauthors. “Increased functional disability over time could be due to worse joint damage, and it has been shown that those who receive later treatment have higher radiological scores at follow-up than those treated early.”
There were 88 deaths in the early treatment group (55%) during the follow-up period, 99 deaths (39.8%) in the late treatment group, and 78 deaths (40.4%) in the never-treated group.
When the researchers adjusted for disease severity in a comparison of mortality across the groups, they found a trend toward a reduced risk of mortality in patients treated early, compared with those who began treatment later, although this did not reach statistical significance.
However, patients in both the early treatment and late treatment groups showed significantly elevated standardized mortality rates, compared with the general population of Norfolk, while the never-treated group showed slightly – but not significantly – elevated mortality.
Overall, around one-quarter of patients (26.6%) began treatment within 6 months of the onset of symptoms, 19.9% were started on treatment within 6-12 months, 17.4% started within 1-2 years, 19% did not start treatment until more than 2 years after symptom onset, and 43.7% of the cohort never received treatment but still attended follow-up.
Patients who began earlier treatment had worse clinical characteristics than did those who began treatment later, except for tender joint counts and autoantibody status.
Researchers saw an overall decline in median swollen joint count and tender joint count in the first year after baseline, and this remained low throughout the course of the study.
Median Health Assessment Questionnaire scores also fell after baseline but then increased steadily from year 2 to year 20, exceeding baseline levels by year 7.
“This paper has two important messages, firstly about the long-term outcome of patients with RA in the modern era treated according to best practice at the time of presentation; secondly about the benefit of early treatment which is still apparent into the second decade after symptom onset with respect to functional disability,” the authors wrote.
An uneven global decline in mortality from RA
Meanwhile, a second study showed that mortality from rheumatoid arthritis declined globally across 31 countries from 1987 to 2011, according to data from the World Health Organization mortality database and the United Nations.
The absolute number of deaths where rheumatoid arthritis was registered as the underlying cause of death declined from 0.12% of all-cause deaths in 1987 to 0.09% of all-cause deaths in 2011 (Arthritis Rheumatol. 2017 April 20. doi: 10.1002/art.40091).
The mean age-standardized mortality rate declined by 48.2%, from 7.1 per million person-years in 1987-1989 to 3.7 in 2009-2011.
However, there was considerable variation between countries; the greatest reduction was seen in Finland, which had an absolute reduction of 20.6 fewer deaths per million person-years, while Croatia had an increase of 3.7 deaths per million person-years.
Younger people with rheumatoid arthritis showed the greatest reductions in mortality, while those in older age groups had smaller reductions in mortality.
“It has been suggested that changes in the management of RA toward early and aggressive treatment with disease-modifying antirheumatic drugs and subsequent biologic therapies has led to better health status and lower mortality for most people with RA over time,” wrote first author Aliasghar A. Kiadaliri, PhD, of Lund (Sweden) University, and his coauthors.
“These findings alongside aging of the population and fall in mortality may lead to an increase in the number of people with RA. Given that it appears that people with RA are now living longer, increase in burden of RA on health care systems is expected and policy makers should be made aware about to appropriately plan for this anticipated increase.”
The first study was supported by Arthritis Research UK. The second study was supported by the Swedish Research Council, Crafoord Foundation, Greta and Johan Kocks Foundation, the Faculty of Medicine Lund University, governmental funding of clinical research within Sweden’s National Health Service. No conflicts of interest were declared for either paper.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: Patients who began treatment with disease-modifying antirheumatic drugs or steroids within 6 months of the onset of symptoms have significantly reduced disability scores up to 20 years later. Also, across 31 countries, the mean age-standardized mortality rate due to RA declined by 48.2%, from 7.1 per million person-years in 1987-1989 to 3.7 in 2009-2011.
Data source: Inception cohort study of 602 patients with rheumatoid arthritis, and a study of World Health Organization and United Nations data from 31 countries.
Disclosures: The first study was supported by Arthritis Research UK. The second study was supported by the Swedish Research Council, Crafoord Foundation, Greta and Johan Kocks Foundation, the Faculty of Medicine Lund University, governmental funding of clinical research within Sweden’s National Health Service. No conflicts of interest were declared for either paper.
Skin testing and decision support can clarify penicillin allergy
Penicillin allergy skin testing or a computerized guideline app with decision support can increase the use of penicillin or cephalosporin among inpatients reporting penicillin allergy.
“Despite a reported penicillin allergy, more than 95% of patients evaluated for such allergy are found penicillin and cephalosporin tolerant,” wrote Kimberly G. Blumenthal, MD, of Massachusetts General Hospital, Boston, and her coauthors.
In this study, they recruited 625 patients reporting penicillin allergy and explored three approaches over three periods of time. These were standard of care, in which penicillin skin testing and test dose challenge is performed only after allergy/immunology consultation; penicillin skin testing performed in all patients not otherwise ineligible for skin testing; and a computerized guideline available on any computer or mobile device within the hospital.
Researchers saw a significant 80% increase in the odds of penicillin or cephalosporin use overall during the period in which the computerized guidelines were available (P = .02).
“The guideline empowered inpatient providers to group allergic reactions into hypersensitivity type, then recommended if and how specific beta-lactam antibiotics [should] be used (i.e. very low risk: full doses; low risk: test doses; medium to high risk: Allergy/Immunology consultation; serious type II-IV hypersensitivity reactions: avoidance),” the authors wrote.
While patients during the skin testing period did not have a significantly increased odds of receiving the antibiotics overall, the adjusted per-protocol analysis showed a nearly sixfold higher odds of receiving penicillin or cephalosporin (odds ratio, 5.7; P less than .001).
Among the 278 patients present during the skin-testing period, 179 (64%) were eligible for skin testing, in that they did not have penicillin intolerances such as gastrointestinal upset, were not taking medications that interfered with skin testing, didn’t have multiple beta-lactam allergies, had not experienced penicillin anaphylaxis in the last 5 years, or had a type II-IV hypersensitivity reaction to penicillin. Of these, 43 (24%) were tested, none of whom were allergic.
The per-protocol analysis of skin testing also showed a 2.5-fold increase in the odds of discharge use of penicillin or cephalosporin (P = .04).
“Since the impact of overreporting penicillin allergy is felt beyond antibiotic utilization to resultant readmissions, treatment failures, and adverse events, safely increasing the use of penicillin and cephalosporin antibiotics in this patient population is a crucial first step towards improved quality of care and reduced cost,” the authors wrote.
The study was supported by the Brigham Care Redesign Incubator and Start-Up Program. No conflicts of interest were declared.
Penicillin allergy skin testing or a computerized guideline app with decision support can increase the use of penicillin or cephalosporin among inpatients reporting penicillin allergy.
“Despite a reported penicillin allergy, more than 95% of patients evaluated for such allergy are found penicillin and cephalosporin tolerant,” wrote Kimberly G. Blumenthal, MD, of Massachusetts General Hospital, Boston, and her coauthors.
In this study, they recruited 625 patients reporting penicillin allergy and explored three approaches over three periods of time. These were standard of care, in which penicillin skin testing and test dose challenge is performed only after allergy/immunology consultation; penicillin skin testing performed in all patients not otherwise ineligible for skin testing; and a computerized guideline available on any computer or mobile device within the hospital.
Researchers saw a significant 80% increase in the odds of penicillin or cephalosporin use overall during the period in which the computerized guidelines were available (P = .02).
“The guideline empowered inpatient providers to group allergic reactions into hypersensitivity type, then recommended if and how specific beta-lactam antibiotics [should] be used (i.e. very low risk: full doses; low risk: test doses; medium to high risk: Allergy/Immunology consultation; serious type II-IV hypersensitivity reactions: avoidance),” the authors wrote.
While patients during the skin testing period did not have a significantly increased odds of receiving the antibiotics overall, the adjusted per-protocol analysis showed a nearly sixfold higher odds of receiving penicillin or cephalosporin (odds ratio, 5.7; P less than .001).
Among the 278 patients present during the skin-testing period, 179 (64%) were eligible for skin testing, in that they did not have penicillin intolerances such as gastrointestinal upset, were not taking medications that interfered with skin testing, didn’t have multiple beta-lactam allergies, had not experienced penicillin anaphylaxis in the last 5 years, or had a type II-IV hypersensitivity reaction to penicillin. Of these, 43 (24%) were tested, none of whom were allergic.
The per-protocol analysis of skin testing also showed a 2.5-fold increase in the odds of discharge use of penicillin or cephalosporin (P = .04).
“Since the impact of overreporting penicillin allergy is felt beyond antibiotic utilization to resultant readmissions, treatment failures, and adverse events, safely increasing the use of penicillin and cephalosporin antibiotics in this patient population is a crucial first step towards improved quality of care and reduced cost,” the authors wrote.
The study was supported by the Brigham Care Redesign Incubator and Start-Up Program. No conflicts of interest were declared.
Penicillin allergy skin testing or a computerized guideline app with decision support can increase the use of penicillin or cephalosporin among inpatients reporting penicillin allergy.
“Despite a reported penicillin allergy, more than 95% of patients evaluated for such allergy are found penicillin and cephalosporin tolerant,” wrote Kimberly G. Blumenthal, MD, of Massachusetts General Hospital, Boston, and her coauthors.
In this study, they recruited 625 patients reporting penicillin allergy and explored three approaches over three periods of time. These were standard of care, in which penicillin skin testing and test dose challenge is performed only after allergy/immunology consultation; penicillin skin testing performed in all patients not otherwise ineligible for skin testing; and a computerized guideline available on any computer or mobile device within the hospital.
Researchers saw a significant 80% increase in the odds of penicillin or cephalosporin use overall during the period in which the computerized guidelines were available (P = .02).
“The guideline empowered inpatient providers to group allergic reactions into hypersensitivity type, then recommended if and how specific beta-lactam antibiotics [should] be used (i.e. very low risk: full doses; low risk: test doses; medium to high risk: Allergy/Immunology consultation; serious type II-IV hypersensitivity reactions: avoidance),” the authors wrote.
While patients during the skin testing period did not have a significantly increased odds of receiving the antibiotics overall, the adjusted per-protocol analysis showed a nearly sixfold higher odds of receiving penicillin or cephalosporin (odds ratio, 5.7; P less than .001).
Among the 278 patients present during the skin-testing period, 179 (64%) were eligible for skin testing, in that they did not have penicillin intolerances such as gastrointestinal upset, were not taking medications that interfered with skin testing, didn’t have multiple beta-lactam allergies, had not experienced penicillin anaphylaxis in the last 5 years, or had a type II-IV hypersensitivity reaction to penicillin. Of these, 43 (24%) were tested, none of whom were allergic.
The per-protocol analysis of skin testing also showed a 2.5-fold increase in the odds of discharge use of penicillin or cephalosporin (P = .04).
“Since the impact of overreporting penicillin allergy is felt beyond antibiotic utilization to resultant readmissions, treatment failures, and adverse events, safely increasing the use of penicillin and cephalosporin antibiotics in this patient population is a crucial first step towards improved quality of care and reduced cost,” the authors wrote.
The study was supported by the Brigham Care Redesign Incubator and Start-Up Program. No conflicts of interest were declared.
FROM THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Key clinical point: Penicillin skin testing or a computerized guideline app with decision support can increase the use of penicillin or cephalosporin among inpatients reporting penicillin allergy.
Major finding: Skin testing and computerized decision support increased the odds of patients’ receiving penicillin or cephalosporin 1.8-5.7 fold.
Data source: A prospective study of 625 inpatients patients reporting penicillin allergy.
Disclosures: The Brigham Care Redesign Incubator and Startup Program supported the study. No conflicts of interest were declared.
Lupus low disease activity definition gains momentum
MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.
The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.
“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”
The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.
While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.
These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.
“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.
In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.
This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.
Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.
“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.
The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.
The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.
Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.
Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.
“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.
In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.
“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”
Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.
The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.
“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”
The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.
While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.
These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.
“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.
In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.
This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.
Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.
“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.
The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.
The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.
Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.
Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.
“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.
In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.
“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”
Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.
The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.
“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”
The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.
While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.
These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.
“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.
In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.
This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.
Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.
“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.
The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.
The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.
Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.
Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.
“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.
In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.
“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”
Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
Key clinical point:
Major finding: The Lupus Low Disease Activity State definition shows significant agreement with clinical judgment and with other endpoints of treatment response, and is associated with a reduced risk of disease flare.
Data source: Three prospective validation studies, two cohort studies, and one clinical trial.
Disclosures: Dr. Nikpour declared research support, honoraria and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies, and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
MicroRNAs linked to treatment response in lupus nephritis
MELBOURNE – Researchers have identified six microRNAs that may indicate a better likelihood of response to cyclophosphamide in patients with lupus nephritis, according to a study presented at an international conference on systemic lupus erythematosus.
“MicroRNA has been shown to be important in systemic lupus in several studies, and they’ve identified several microRNA that have been shown to affect the outcome measures in patients,” said Sarfaraz Hasni, MD, director of the Lupus Clinical Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., who presented a poster on the study at the meeting.
The aim of this study, involving 71 patients with lupus nephritis, was to look for microRNAs associated with treatment response to cyclophosphamide.
The first stage of the study involved isolating microRNAs from kidney biopsies taken from a first cohort of 17 responders and 15 nonresponders.
Responders were patients who, after 2 years of intravenous cyclophosphamide, showed no active urinary sediments, less than five red blood cells or white blood cells in urine, and proteinuria below 1 g/24 hours.
After analyzing 300-400 microRNAs in these biopsies, the investigators identified 6 that were significantly upregulated in association with treatment outcome in both the first cohort as well as a second validation cohort of 22 responders and 17 nonresponders.
When the researchers looked at the most likely genetic targets of these microRNAs, they identified genes associated with G2/M DNA damage checkpoint regulation, which points to a link with cyclophosphamide efficacy, as well as associations with immunological disease and renal inflammation.
Dr. Hasni said that previous studies of microRNA had looked in the peripheral blood but suggested this may not necessarily reflect what was happening in the kidney.
The next step for researchers is to see if upregulation of these microRNAs is predictive of treatment response.
“If you are giving cyclophosphamide for 2 years, it comes with a high risk of side effects, especially in young women because there is potential for premature ovarian failure,” Dr. Hasni said in an interview. “If we can predict that this patient is not going to respond to cyclophosphamide or will not have a good outcome, we can use alternative therapy, or perhaps use more aggressive or a combination therapy approach rather than keep doing the same thing and 2 years later find out the patient is not going to respond.”
The researchers are also keen to investigate whether these same microRNAs can be isolated from serum or urine, which would reduce the need for kidney biopsy.
“The testing for microRNA is not that hard – it’s the biopsy and extracting the tissue from the biopsy... that’s obviously cumbersome and can only be done in a research setting.”
No conflicts of interest were declared.
MELBOURNE – Researchers have identified six microRNAs that may indicate a better likelihood of response to cyclophosphamide in patients with lupus nephritis, according to a study presented at an international conference on systemic lupus erythematosus.
“MicroRNA has been shown to be important in systemic lupus in several studies, and they’ve identified several microRNA that have been shown to affect the outcome measures in patients,” said Sarfaraz Hasni, MD, director of the Lupus Clinical Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., who presented a poster on the study at the meeting.
The aim of this study, involving 71 patients with lupus nephritis, was to look for microRNAs associated with treatment response to cyclophosphamide.
The first stage of the study involved isolating microRNAs from kidney biopsies taken from a first cohort of 17 responders and 15 nonresponders.
Responders were patients who, after 2 years of intravenous cyclophosphamide, showed no active urinary sediments, less than five red blood cells or white blood cells in urine, and proteinuria below 1 g/24 hours.
After analyzing 300-400 microRNAs in these biopsies, the investigators identified 6 that were significantly upregulated in association with treatment outcome in both the first cohort as well as a second validation cohort of 22 responders and 17 nonresponders.
When the researchers looked at the most likely genetic targets of these microRNAs, they identified genes associated with G2/M DNA damage checkpoint regulation, which points to a link with cyclophosphamide efficacy, as well as associations with immunological disease and renal inflammation.
Dr. Hasni said that previous studies of microRNA had looked in the peripheral blood but suggested this may not necessarily reflect what was happening in the kidney.
The next step for researchers is to see if upregulation of these microRNAs is predictive of treatment response.
“If you are giving cyclophosphamide for 2 years, it comes with a high risk of side effects, especially in young women because there is potential for premature ovarian failure,” Dr. Hasni said in an interview. “If we can predict that this patient is not going to respond to cyclophosphamide or will not have a good outcome, we can use alternative therapy, or perhaps use more aggressive or a combination therapy approach rather than keep doing the same thing and 2 years later find out the patient is not going to respond.”
The researchers are also keen to investigate whether these same microRNAs can be isolated from serum or urine, which would reduce the need for kidney biopsy.
“The testing for microRNA is not that hard – it’s the biopsy and extracting the tissue from the biopsy... that’s obviously cumbersome and can only be done in a research setting.”
No conflicts of interest were declared.
MELBOURNE – Researchers have identified six microRNAs that may indicate a better likelihood of response to cyclophosphamide in patients with lupus nephritis, according to a study presented at an international conference on systemic lupus erythematosus.
“MicroRNA has been shown to be important in systemic lupus in several studies, and they’ve identified several microRNA that have been shown to affect the outcome measures in patients,” said Sarfaraz Hasni, MD, director of the Lupus Clinical Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., who presented a poster on the study at the meeting.
The aim of this study, involving 71 patients with lupus nephritis, was to look for microRNAs associated with treatment response to cyclophosphamide.
The first stage of the study involved isolating microRNAs from kidney biopsies taken from a first cohort of 17 responders and 15 nonresponders.
Responders were patients who, after 2 years of intravenous cyclophosphamide, showed no active urinary sediments, less than five red blood cells or white blood cells in urine, and proteinuria below 1 g/24 hours.
After analyzing 300-400 microRNAs in these biopsies, the investigators identified 6 that were significantly upregulated in association with treatment outcome in both the first cohort as well as a second validation cohort of 22 responders and 17 nonresponders.
When the researchers looked at the most likely genetic targets of these microRNAs, they identified genes associated with G2/M DNA damage checkpoint regulation, which points to a link with cyclophosphamide efficacy, as well as associations with immunological disease and renal inflammation.
Dr. Hasni said that previous studies of microRNA had looked in the peripheral blood but suggested this may not necessarily reflect what was happening in the kidney.
The next step for researchers is to see if upregulation of these microRNAs is predictive of treatment response.
“If you are giving cyclophosphamide for 2 years, it comes with a high risk of side effects, especially in young women because there is potential for premature ovarian failure,” Dr. Hasni said in an interview. “If we can predict that this patient is not going to respond to cyclophosphamide or will not have a good outcome, we can use alternative therapy, or perhaps use more aggressive or a combination therapy approach rather than keep doing the same thing and 2 years later find out the patient is not going to respond.”
The researchers are also keen to investigate whether these same microRNAs can be isolated from serum or urine, which would reduce the need for kidney biopsy.
“The testing for microRNA is not that hard – it’s the biopsy and extracting the tissue from the biopsy... that’s obviously cumbersome and can only be done in a research setting.”
No conflicts of interest were declared.
AT LUPUS 2017
Key clinical point:
Major finding: Researchers have identified six microRNAs from kidney biopsies that are significantly upregulated in patients who respond to cyclophosphamide treatment for lupus nephritis.
Data source: Prospective cohort study in 71 patients with lupus nephritis.
Disclosures: No conflicts of interest were declared.
Belimumab response at 2 years achieved by two-thirds of lupus patients
MELBOURNE – Two-thirds of patients with active systemic lupus erythematosus responded to treatment with belimumab at 2 years in a clinical practice setting, particularly those with higher disease activity or polyarthritis, according to data presented at an international conference on systemic lupus erythematosus.
In a multicenter prospective study of 188 patients with active systemic lupus erythematosus (SLE), Maddalena Larosa, MD, of the University of Padova (Italy) and her colleagues reported a 71.3% response rate with belimumab (Benlysta) at 12 months based on achieving SLE Responder Index (SRI-4) criteria. SRI-4 is a composite endpoint requiring at least a 4-point reduction in SLE Disease Activity Index 2000 (SLEDAI-2K) score, no worsening (less than 10-mm increase) from baseline in the Physician’s Global Assessment of Disease Activity score (PGA), and no new British Isles Lupus Assessment Group (BILAG) Domain A and no more than 1 new BILAG Domain B scores.
Patients were treated with belimumab as an add-on to standard care, with a treatment regimen of 10 mg/kg at day 0, 14, 28, and then every 28 days. The mean SLEDAI-2K score among patients was 8.3, all were positive for double-stranded DNA autoantibodies, and the mean Systemic Lupus International Collaborative Clinics (SLICC) Damage Index was 0.84. Nearly two-thirds of patients were also being treated with immunosuppressants.
Patients with a SLEDAI-2K score of 10 or above were 25 times more likely to respond by 12 months and 12 times more likely to respond by 24 months, both of which were statistically significant.
Similarly, patients with polyarthritis – who constituted nearly half of all patients in the study – were 8 times more likely to respond at 12 months, and 32 times more likely to respond at 24 months. Patients on a prednisone dose of 7.5 mg/day or greater were also significantly more likely to respond at 24 months.
“What was surprising in these patients who respond better are patients with higher disease activity,” Dr. Larosa said in an interview, noting that many patients had also had refractory disease.
Belimumab treatment was also associated with a plateauing of damage accrual, as measured by the SLICC Damage Index, she said.
“In the 5 years before belimumab initiation, we observed an increase of damage accrual related to SLE, but after the first belimumab infusion we did not observe any increase of damage accrual related to the disease,” Dr. Larosa told the audience.
The median duration of treatment was 12 months, but 58 patients (30.9%) discontinued belimumab, mainly because of adverse events. Eight patients also discontinued because of pregnancy, and two because of remission.
In response to a question on the effect of treatment on flare, Dr. Larosa said the treatment was also associated with a reduction in the number of patients who experienced flares, and a significant reduction in renal flares in patients with renal involvement.
No conflicts of interest were declared.
MELBOURNE – Two-thirds of patients with active systemic lupus erythematosus responded to treatment with belimumab at 2 years in a clinical practice setting, particularly those with higher disease activity or polyarthritis, according to data presented at an international conference on systemic lupus erythematosus.
In a multicenter prospective study of 188 patients with active systemic lupus erythematosus (SLE), Maddalena Larosa, MD, of the University of Padova (Italy) and her colleagues reported a 71.3% response rate with belimumab (Benlysta) at 12 months based on achieving SLE Responder Index (SRI-4) criteria. SRI-4 is a composite endpoint requiring at least a 4-point reduction in SLE Disease Activity Index 2000 (SLEDAI-2K) score, no worsening (less than 10-mm increase) from baseline in the Physician’s Global Assessment of Disease Activity score (PGA), and no new British Isles Lupus Assessment Group (BILAG) Domain A and no more than 1 new BILAG Domain B scores.
Patients were treated with belimumab as an add-on to standard care, with a treatment regimen of 10 mg/kg at day 0, 14, 28, and then every 28 days. The mean SLEDAI-2K score among patients was 8.3, all were positive for double-stranded DNA autoantibodies, and the mean Systemic Lupus International Collaborative Clinics (SLICC) Damage Index was 0.84. Nearly two-thirds of patients were also being treated with immunosuppressants.
Patients with a SLEDAI-2K score of 10 or above were 25 times more likely to respond by 12 months and 12 times more likely to respond by 24 months, both of which were statistically significant.
Similarly, patients with polyarthritis – who constituted nearly half of all patients in the study – were 8 times more likely to respond at 12 months, and 32 times more likely to respond at 24 months. Patients on a prednisone dose of 7.5 mg/day or greater were also significantly more likely to respond at 24 months.
“What was surprising in these patients who respond better are patients with higher disease activity,” Dr. Larosa said in an interview, noting that many patients had also had refractory disease.
Belimumab treatment was also associated with a plateauing of damage accrual, as measured by the SLICC Damage Index, she said.
“In the 5 years before belimumab initiation, we observed an increase of damage accrual related to SLE, but after the first belimumab infusion we did not observe any increase of damage accrual related to the disease,” Dr. Larosa told the audience.
The median duration of treatment was 12 months, but 58 patients (30.9%) discontinued belimumab, mainly because of adverse events. Eight patients also discontinued because of pregnancy, and two because of remission.
In response to a question on the effect of treatment on flare, Dr. Larosa said the treatment was also associated with a reduction in the number of patients who experienced flares, and a significant reduction in renal flares in patients with renal involvement.
No conflicts of interest were declared.
MELBOURNE – Two-thirds of patients with active systemic lupus erythematosus responded to treatment with belimumab at 2 years in a clinical practice setting, particularly those with higher disease activity or polyarthritis, according to data presented at an international conference on systemic lupus erythematosus.
In a multicenter prospective study of 188 patients with active systemic lupus erythematosus (SLE), Maddalena Larosa, MD, of the University of Padova (Italy) and her colleagues reported a 71.3% response rate with belimumab (Benlysta) at 12 months based on achieving SLE Responder Index (SRI-4) criteria. SRI-4 is a composite endpoint requiring at least a 4-point reduction in SLE Disease Activity Index 2000 (SLEDAI-2K) score, no worsening (less than 10-mm increase) from baseline in the Physician’s Global Assessment of Disease Activity score (PGA), and no new British Isles Lupus Assessment Group (BILAG) Domain A and no more than 1 new BILAG Domain B scores.
Patients were treated with belimumab as an add-on to standard care, with a treatment regimen of 10 mg/kg at day 0, 14, 28, and then every 28 days. The mean SLEDAI-2K score among patients was 8.3, all were positive for double-stranded DNA autoantibodies, and the mean Systemic Lupus International Collaborative Clinics (SLICC) Damage Index was 0.84. Nearly two-thirds of patients were also being treated with immunosuppressants.
Patients with a SLEDAI-2K score of 10 or above were 25 times more likely to respond by 12 months and 12 times more likely to respond by 24 months, both of which were statistically significant.
Similarly, patients with polyarthritis – who constituted nearly half of all patients in the study – were 8 times more likely to respond at 12 months, and 32 times more likely to respond at 24 months. Patients on a prednisone dose of 7.5 mg/day or greater were also significantly more likely to respond at 24 months.
“What was surprising in these patients who respond better are patients with higher disease activity,” Dr. Larosa said in an interview, noting that many patients had also had refractory disease.
Belimumab treatment was also associated with a plateauing of damage accrual, as measured by the SLICC Damage Index, she said.
“In the 5 years before belimumab initiation, we observed an increase of damage accrual related to SLE, but after the first belimumab infusion we did not observe any increase of damage accrual related to the disease,” Dr. Larosa told the audience.
The median duration of treatment was 12 months, but 58 patients (30.9%) discontinued belimumab, mainly because of adverse events. Eight patients also discontinued because of pregnancy, and two because of remission.
In response to a question on the effect of treatment on flare, Dr. Larosa said the treatment was also associated with a reduction in the number of patients who experienced flares, and a significant reduction in renal flares in patients with renal involvement.
No conflicts of interest were declared.
AT LUPUS 2017
Key clinical point:
Major finding: Belimumab as an add-on therapy in systemic lupus erythematosus was associated with a 71.3% response rate at 12 months and 68.7% response rate at 24 months.
Data source: Prospective, multicenter cohort study of 188 patients with systemic lupus erythematosus.
Disclosures: No conflicts of interest were declared.
Incorporate steroid dose into lupus disease activity score, expert says
MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.
Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.
“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”
The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.
In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.
The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.
Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.
“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”
Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.
However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.
“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”
The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.
MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.
Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.
“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”
The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.
In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.
The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.
Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.
“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”
Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.
However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.
“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”
The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.
MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.
Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.
“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”
The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.
In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.
The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.
Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.
“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”
Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.
However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.
“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”
The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.
AT LUPUS 2017
Key clinical point:
Major finding: A revised SLEDAI incorporating glucocorticoid dose was significantly better at predicting damage accrual.
Data source: Development of a new disease activity index from 131 patient scenarios derived from a longitudinal cohort and validated in a separate inception cohort.
Disclosures: The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.
Lupus nephritis expert offers management tips
MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.
In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.
Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.
He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.
“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”
Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.
“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”
Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.
“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”
He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.
“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”
Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.
He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.
Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.
“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.
Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.
Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.
MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.
In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.
Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.
He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.
“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”
Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.
“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”
Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.
“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”
He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.
“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”
Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.
He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.
Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.
“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.
Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.
Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.
MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.
In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.
Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.
He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.
“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”
Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.
“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”
Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.
“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”
He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.
“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”
Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.
He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.
Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.
“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.
Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.
Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.
EXPERT ANALYSIS FROM LUPUS 2017
Vascular involvement may signify worse outcomes in lupus nephritis
MELBOURNE – Vascular involvement in patients with lupus nephritis is associated with poorer outcomes and could be a trigger for a more aggressive treatment approach, according to observational study results reported at an international congress on systemic lupus erythematosus.
Manish Rathi, MD, a nephrologist at the Postgraduate Institution of Medical Education & Research in Chandigarh, India, reported the results of a 5-year prospective cohort study in 241 patients with biopsy-proven lupus nephritis.
Researchers found that patients with vascular involvement had significantly higher serum creatinine at baseline than did those without it. At follow-up, they also had significantly higher proteinuria and serum creatinine, as well as significantly lower serum albumin.
This group was also less likely to achieve complete remission, compared with patients without vascular involvement (38.2% vs. 61.9%; P = .006), and had treatment-refractory disease almost twice as often (26.3% vs. 14.3%; P = .02).
Overall, vascular involvement was seen in 32.3% of patients, with the most common form being arteriosclerosis (22.8%), followed by vascular thrombotic microangiopathy (11.2%), asymptomatic vascular immune deposits (5.3%), vasculopathy (2%), and vasculitis (0.8%).
Three-quarters of all patients had nephrotic syndrome, and 41.9% were identified as Class IV, 18.7% as Class V, 10.4% as Class III, and 3.7% as Class II.
When researchers examined the presentation and outcomes among these subgroups, they found that patients with vascular thrombotic microangiopathy had a significantly higher serum creatinine and were less likely to respond to treatment, compared with patients without vascular thrombotic microangiopathy (60% vs. 79.1%).
Similarly, patients with arteriosclerosis had significantly lower incidence of complete remission, compared with those without arteriosclerosis (37.7% vs. 58.8%) although they had significantly higher rates of partial remission (35.8% vs. 19.4%).
“Lupus patients, if they had involvement of vascular compartment, they had more severe presentation at the time of presentation as well as poorer outcomes despite giving the standard therapy,” Dr. Rathi said.
In an interview, Dr. Rathi said the results had already influenced their own treatment approach with these patients.
“What we have started doing now is – if there is vascular involvement, particularly the thrombotic microangiopathy – we treat them as severe lupus nephritis [patients], so even if their class of lupus nephritis is less severe, we’ll be treating them as severe,” he said.
Commenting on the presentation, Frederic Houssiau, MD, PhD, a professor of rheumatology at the Cliniques Universitaires Saint-Luc in Brussels, said he agreed that vascular involvement was neglected in the current classification of lupus nephritis and that it should be taken into account.
“Maybe we should not only consider the class but also look in more detail to the pathophysiological findings,” Dr. Houssiau said in an interview. “When you have a lot of inflammation in the vessels, for instance, maybe we should use cyclophosphamide.”
No conflicts of interest were disclosed.
MELBOURNE – Vascular involvement in patients with lupus nephritis is associated with poorer outcomes and could be a trigger for a more aggressive treatment approach, according to observational study results reported at an international congress on systemic lupus erythematosus.
Manish Rathi, MD, a nephrologist at the Postgraduate Institution of Medical Education & Research in Chandigarh, India, reported the results of a 5-year prospective cohort study in 241 patients with biopsy-proven lupus nephritis.
Researchers found that patients with vascular involvement had significantly higher serum creatinine at baseline than did those without it. At follow-up, they also had significantly higher proteinuria and serum creatinine, as well as significantly lower serum albumin.
This group was also less likely to achieve complete remission, compared with patients without vascular involvement (38.2% vs. 61.9%; P = .006), and had treatment-refractory disease almost twice as often (26.3% vs. 14.3%; P = .02).
Overall, vascular involvement was seen in 32.3% of patients, with the most common form being arteriosclerosis (22.8%), followed by vascular thrombotic microangiopathy (11.2%), asymptomatic vascular immune deposits (5.3%), vasculopathy (2%), and vasculitis (0.8%).
Three-quarters of all patients had nephrotic syndrome, and 41.9% were identified as Class IV, 18.7% as Class V, 10.4% as Class III, and 3.7% as Class II.
When researchers examined the presentation and outcomes among these subgroups, they found that patients with vascular thrombotic microangiopathy had a significantly higher serum creatinine and were less likely to respond to treatment, compared with patients without vascular thrombotic microangiopathy (60% vs. 79.1%).
Similarly, patients with arteriosclerosis had significantly lower incidence of complete remission, compared with those without arteriosclerosis (37.7% vs. 58.8%) although they had significantly higher rates of partial remission (35.8% vs. 19.4%).
“Lupus patients, if they had involvement of vascular compartment, they had more severe presentation at the time of presentation as well as poorer outcomes despite giving the standard therapy,” Dr. Rathi said.
In an interview, Dr. Rathi said the results had already influenced their own treatment approach with these patients.
“What we have started doing now is – if there is vascular involvement, particularly the thrombotic microangiopathy – we treat them as severe lupus nephritis [patients], so even if their class of lupus nephritis is less severe, we’ll be treating them as severe,” he said.
Commenting on the presentation, Frederic Houssiau, MD, PhD, a professor of rheumatology at the Cliniques Universitaires Saint-Luc in Brussels, said he agreed that vascular involvement was neglected in the current classification of lupus nephritis and that it should be taken into account.
“Maybe we should not only consider the class but also look in more detail to the pathophysiological findings,” Dr. Houssiau said in an interview. “When you have a lot of inflammation in the vessels, for instance, maybe we should use cyclophosphamide.”
No conflicts of interest were disclosed.
MELBOURNE – Vascular involvement in patients with lupus nephritis is associated with poorer outcomes and could be a trigger for a more aggressive treatment approach, according to observational study results reported at an international congress on systemic lupus erythematosus.
Manish Rathi, MD, a nephrologist at the Postgraduate Institution of Medical Education & Research in Chandigarh, India, reported the results of a 5-year prospective cohort study in 241 patients with biopsy-proven lupus nephritis.
Researchers found that patients with vascular involvement had significantly higher serum creatinine at baseline than did those without it. At follow-up, they also had significantly higher proteinuria and serum creatinine, as well as significantly lower serum albumin.
This group was also less likely to achieve complete remission, compared with patients without vascular involvement (38.2% vs. 61.9%; P = .006), and had treatment-refractory disease almost twice as often (26.3% vs. 14.3%; P = .02).
Overall, vascular involvement was seen in 32.3% of patients, with the most common form being arteriosclerosis (22.8%), followed by vascular thrombotic microangiopathy (11.2%), asymptomatic vascular immune deposits (5.3%), vasculopathy (2%), and vasculitis (0.8%).
Three-quarters of all patients had nephrotic syndrome, and 41.9% were identified as Class IV, 18.7% as Class V, 10.4% as Class III, and 3.7% as Class II.
When researchers examined the presentation and outcomes among these subgroups, they found that patients with vascular thrombotic microangiopathy had a significantly higher serum creatinine and were less likely to respond to treatment, compared with patients without vascular thrombotic microangiopathy (60% vs. 79.1%).
Similarly, patients with arteriosclerosis had significantly lower incidence of complete remission, compared with those without arteriosclerosis (37.7% vs. 58.8%) although they had significantly higher rates of partial remission (35.8% vs. 19.4%).
“Lupus patients, if they had involvement of vascular compartment, they had more severe presentation at the time of presentation as well as poorer outcomes despite giving the standard therapy,” Dr. Rathi said.
In an interview, Dr. Rathi said the results had already influenced their own treatment approach with these patients.
“What we have started doing now is – if there is vascular involvement, particularly the thrombotic microangiopathy – we treat them as severe lupus nephritis [patients], so even if their class of lupus nephritis is less severe, we’ll be treating them as severe,” he said.
Commenting on the presentation, Frederic Houssiau, MD, PhD, a professor of rheumatology at the Cliniques Universitaires Saint-Luc in Brussels, said he agreed that vascular involvement was neglected in the current classification of lupus nephritis and that it should be taken into account.
“Maybe we should not only consider the class but also look in more detail to the pathophysiological findings,” Dr. Houssiau said in an interview. “When you have a lot of inflammation in the vessels, for instance, maybe we should use cyclophosphamide.”
No conflicts of interest were disclosed.
AT LUPUS 2017
Key clinical point:
Major finding: Patients with vascular involvement in lupus nephritis are significantly less likely to achieve complete remission and have higher rates of treatment-refractory disease.
Data source: An observational cohort study in 241 patients with biopsy-proven lupus nephritis.
Disclosures: No conflicts of interest were declared.