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Drug-free inactive disease a feasible goal in JIA
Recent recommendations from an international task force advocating that have been backed up by research that finds the goal is a feasible one.
Published online in the Annals of the Rheumatic Diseases, the investigator-initiated, multicenter, randomized BEST for Kids study found that, regardless of initial specific treatments, after 24 months of treatment to target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (at a median onset of 9 months), and 39% were drug free.
The investigators, led by Petra Hissink Muller, MD, department of pediatrics, Leiden (the Netherlands) University Medical Center said previous studies of JIA supported the “window of opportunity” hypothesis in which disease optimally responds to treatment.
“In JIA, continuous treatment-to-target therapy in a tight control setting, with treatment adjustments based on frequent evaluations of disease activity, has not yet been studied. Recent recommendations agree that treatment to target should be implemented in daily practice,” they wrote.
The aim of the BEST for Kids study was to investigate which of three frequently used treatment-to-target strategies was most effective and safe.
Overall, 94 children (67% girls) with a median age of 9.1 years with new-onset (oligoarticular, juvenile psoriatic arthritis, or rheumatoid factor–negative polyarticular) JIA, without previous disease-modifying antirheumatic drug (DMARD) therapy and symptom duration of less than 18 months were enrolled in the study.
Median symptom duration was 7.5 months and median duration between diagnosis and inclusion in the study was 6 weeks. The investigators noted that two patients left the study during follow-up because of a revised diagnosis.
All study participants were randomized into three strategy arms:
- Initial treatment with conventional synthetic DMARD monotherapy (methotrexate [MTX] or sulfasalazine if preferred by treating physician), n = 32.
- Initial treatment with MTX and 6 weeks of tapered prednisolone (‘bridging therapy), n = 32).
- Initial treatment with MTX and etanercept, n = 30.
In case of inactive disease for at least 3 (oligoarticular disease) or 6 (polyarticular disease) consecutive months, DMARDs were tapered and stopped in all three arms. For combination therapy, etanercept was tapered to once every 2 weeks, followed by a 50% dose reduction, then halted. The dose of MTX or sulfasalazine was reduced by 25% per week to zero.
In case of a disease flare, the last discontinued drug and/or the last effective dose was reintroduced. The protocol did not allow prednisolone to be restarted, whereas etanercept could be restarted but not discontinued for a second time.
The primary outcome of the trial was time to inactive disease and time to flare (defined as the time between first moment of drug-free inactive disease (DFID) and the first arthritis flare as judged by the treating physician) after tapering and stopping all DMARD therapy. Secondary outcomes were adapted ACR Pediatric (ACR Pedi) 30/50/70/90 scores, functional ability, and adverse events.
Results showed that after 24 months inactive disease was achieved by more than 70% of the patients (71%, arm 1; 70%, arm 2; and 72%, arm 3).
Furthermore, drug-free inactive disease (DFID) was achieved by 59% of the cohort (54 of 92 patients; 45% of arm 1, 31% of arm 2, and 41% of arm 3), although the authors noted that early flares did occur in 14 patients and were successfully retreated, resulting in 39% of the patients in DFID at the 2-year study endpoint.
In the treatment of JIA,“we showed that tapering and discontinuation of treatment is a realistic goal. On the other hand, treatment to target resulted in a relatively high use of [biologic] DMARDs, greater than 50% of patients in all arms,” the investigators wrote.
Median time to inactive disease was 9 months in all arms (P = .30), and time to flare was also not significantly different among the groups (overall 3 months [3.0-6.8]; P = .7). The investigators noted that while overall flare rates (26%) were lower than the 37%-60% mentioned in previous cohorts, this finding could be a result of the limited follow-up time.
After 3 months of treatment, more patients who started with MTX and etanercept (arm 3) had achieved rapid improvement as determined by ACR Pedi 70 scores. However, the investigators noted that, because of treatment adjustments in cases of active disease, which were needed more often in arms 1 and 2 than in arm 3, ACR Pedi improvement scores were met in similar percentages of patients over time across the arms.
Adverse events were similar across treatment arms and were generally mild, involving mostly gastrointestinal complaints, upper respiratory tract and other infections, and general malaise.
Overall, the investigators concluded that DFID was a “feasible goal” in the treatment of children with JIA.
Limitations of the study included breaches of treatment protocol by physicians in patients across the three arms.“The physicians did not follow protocol for various reasons, mainly reluctance to intensify therapy based on shared decision making,” they wrote.
Another limitation was the small sample size, which the investigators said could obscure differences between groups that in a larger population might have become clear.
“Long-term follow-up of the BEST for Kids cohort, including radiology results, is initiated to investigate possible lasting positive results of treatment to target in JIA,” they said.
SOURCE: Hissink Muller P et al. Ann Rheum Dis. Oct 12. doi: 10.1136/annrheumdis-2018-213902.
Recent recommendations from an international task force advocating that have been backed up by research that finds the goal is a feasible one.
Published online in the Annals of the Rheumatic Diseases, the investigator-initiated, multicenter, randomized BEST for Kids study found that, regardless of initial specific treatments, after 24 months of treatment to target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (at a median onset of 9 months), and 39% were drug free.
The investigators, led by Petra Hissink Muller, MD, department of pediatrics, Leiden (the Netherlands) University Medical Center said previous studies of JIA supported the “window of opportunity” hypothesis in which disease optimally responds to treatment.
“In JIA, continuous treatment-to-target therapy in a tight control setting, with treatment adjustments based on frequent evaluations of disease activity, has not yet been studied. Recent recommendations agree that treatment to target should be implemented in daily practice,” they wrote.
The aim of the BEST for Kids study was to investigate which of three frequently used treatment-to-target strategies was most effective and safe.
Overall, 94 children (67% girls) with a median age of 9.1 years with new-onset (oligoarticular, juvenile psoriatic arthritis, or rheumatoid factor–negative polyarticular) JIA, without previous disease-modifying antirheumatic drug (DMARD) therapy and symptom duration of less than 18 months were enrolled in the study.
Median symptom duration was 7.5 months and median duration between diagnosis and inclusion in the study was 6 weeks. The investigators noted that two patients left the study during follow-up because of a revised diagnosis.
All study participants were randomized into three strategy arms:
- Initial treatment with conventional synthetic DMARD monotherapy (methotrexate [MTX] or sulfasalazine if preferred by treating physician), n = 32.
- Initial treatment with MTX and 6 weeks of tapered prednisolone (‘bridging therapy), n = 32).
- Initial treatment with MTX and etanercept, n = 30.
In case of inactive disease for at least 3 (oligoarticular disease) or 6 (polyarticular disease) consecutive months, DMARDs were tapered and stopped in all three arms. For combination therapy, etanercept was tapered to once every 2 weeks, followed by a 50% dose reduction, then halted. The dose of MTX or sulfasalazine was reduced by 25% per week to zero.
In case of a disease flare, the last discontinued drug and/or the last effective dose was reintroduced. The protocol did not allow prednisolone to be restarted, whereas etanercept could be restarted but not discontinued for a second time.
The primary outcome of the trial was time to inactive disease and time to flare (defined as the time between first moment of drug-free inactive disease (DFID) and the first arthritis flare as judged by the treating physician) after tapering and stopping all DMARD therapy. Secondary outcomes were adapted ACR Pediatric (ACR Pedi) 30/50/70/90 scores, functional ability, and adverse events.
Results showed that after 24 months inactive disease was achieved by more than 70% of the patients (71%, arm 1; 70%, arm 2; and 72%, arm 3).
Furthermore, drug-free inactive disease (DFID) was achieved by 59% of the cohort (54 of 92 patients; 45% of arm 1, 31% of arm 2, and 41% of arm 3), although the authors noted that early flares did occur in 14 patients and were successfully retreated, resulting in 39% of the patients in DFID at the 2-year study endpoint.
In the treatment of JIA,“we showed that tapering and discontinuation of treatment is a realistic goal. On the other hand, treatment to target resulted in a relatively high use of [biologic] DMARDs, greater than 50% of patients in all arms,” the investigators wrote.
Median time to inactive disease was 9 months in all arms (P = .30), and time to flare was also not significantly different among the groups (overall 3 months [3.0-6.8]; P = .7). The investigators noted that while overall flare rates (26%) were lower than the 37%-60% mentioned in previous cohorts, this finding could be a result of the limited follow-up time.
After 3 months of treatment, more patients who started with MTX and etanercept (arm 3) had achieved rapid improvement as determined by ACR Pedi 70 scores. However, the investigators noted that, because of treatment adjustments in cases of active disease, which were needed more often in arms 1 and 2 than in arm 3, ACR Pedi improvement scores were met in similar percentages of patients over time across the arms.
Adverse events were similar across treatment arms and were generally mild, involving mostly gastrointestinal complaints, upper respiratory tract and other infections, and general malaise.
Overall, the investigators concluded that DFID was a “feasible goal” in the treatment of children with JIA.
Limitations of the study included breaches of treatment protocol by physicians in patients across the three arms.“The physicians did not follow protocol for various reasons, mainly reluctance to intensify therapy based on shared decision making,” they wrote.
Another limitation was the small sample size, which the investigators said could obscure differences between groups that in a larger population might have become clear.
“Long-term follow-up of the BEST for Kids cohort, including radiology results, is initiated to investigate possible lasting positive results of treatment to target in JIA,” they said.
SOURCE: Hissink Muller P et al. Ann Rheum Dis. Oct 12. doi: 10.1136/annrheumdis-2018-213902.
Recent recommendations from an international task force advocating that have been backed up by research that finds the goal is a feasible one.
Published online in the Annals of the Rheumatic Diseases, the investigator-initiated, multicenter, randomized BEST for Kids study found that, regardless of initial specific treatments, after 24 months of treatment to target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (at a median onset of 9 months), and 39% were drug free.
The investigators, led by Petra Hissink Muller, MD, department of pediatrics, Leiden (the Netherlands) University Medical Center said previous studies of JIA supported the “window of opportunity” hypothesis in which disease optimally responds to treatment.
“In JIA, continuous treatment-to-target therapy in a tight control setting, with treatment adjustments based on frequent evaluations of disease activity, has not yet been studied. Recent recommendations agree that treatment to target should be implemented in daily practice,” they wrote.
The aim of the BEST for Kids study was to investigate which of three frequently used treatment-to-target strategies was most effective and safe.
Overall, 94 children (67% girls) with a median age of 9.1 years with new-onset (oligoarticular, juvenile psoriatic arthritis, or rheumatoid factor–negative polyarticular) JIA, without previous disease-modifying antirheumatic drug (DMARD) therapy and symptom duration of less than 18 months were enrolled in the study.
Median symptom duration was 7.5 months and median duration between diagnosis and inclusion in the study was 6 weeks. The investigators noted that two patients left the study during follow-up because of a revised diagnosis.
All study participants were randomized into three strategy arms:
- Initial treatment with conventional synthetic DMARD monotherapy (methotrexate [MTX] or sulfasalazine if preferred by treating physician), n = 32.
- Initial treatment with MTX and 6 weeks of tapered prednisolone (‘bridging therapy), n = 32).
- Initial treatment with MTX and etanercept, n = 30.
In case of inactive disease for at least 3 (oligoarticular disease) or 6 (polyarticular disease) consecutive months, DMARDs were tapered and stopped in all three arms. For combination therapy, etanercept was tapered to once every 2 weeks, followed by a 50% dose reduction, then halted. The dose of MTX or sulfasalazine was reduced by 25% per week to zero.
In case of a disease flare, the last discontinued drug and/or the last effective dose was reintroduced. The protocol did not allow prednisolone to be restarted, whereas etanercept could be restarted but not discontinued for a second time.
The primary outcome of the trial was time to inactive disease and time to flare (defined as the time between first moment of drug-free inactive disease (DFID) and the first arthritis flare as judged by the treating physician) after tapering and stopping all DMARD therapy. Secondary outcomes were adapted ACR Pediatric (ACR Pedi) 30/50/70/90 scores, functional ability, and adverse events.
Results showed that after 24 months inactive disease was achieved by more than 70% of the patients (71%, arm 1; 70%, arm 2; and 72%, arm 3).
Furthermore, drug-free inactive disease (DFID) was achieved by 59% of the cohort (54 of 92 patients; 45% of arm 1, 31% of arm 2, and 41% of arm 3), although the authors noted that early flares did occur in 14 patients and were successfully retreated, resulting in 39% of the patients in DFID at the 2-year study endpoint.
In the treatment of JIA,“we showed that tapering and discontinuation of treatment is a realistic goal. On the other hand, treatment to target resulted in a relatively high use of [biologic] DMARDs, greater than 50% of patients in all arms,” the investigators wrote.
Median time to inactive disease was 9 months in all arms (P = .30), and time to flare was also not significantly different among the groups (overall 3 months [3.0-6.8]; P = .7). The investigators noted that while overall flare rates (26%) were lower than the 37%-60% mentioned in previous cohorts, this finding could be a result of the limited follow-up time.
After 3 months of treatment, more patients who started with MTX and etanercept (arm 3) had achieved rapid improvement as determined by ACR Pedi 70 scores. However, the investigators noted that, because of treatment adjustments in cases of active disease, which were needed more often in arms 1 and 2 than in arm 3, ACR Pedi improvement scores were met in similar percentages of patients over time across the arms.
Adverse events were similar across treatment arms and were generally mild, involving mostly gastrointestinal complaints, upper respiratory tract and other infections, and general malaise.
Overall, the investigators concluded that DFID was a “feasible goal” in the treatment of children with JIA.
Limitations of the study included breaches of treatment protocol by physicians in patients across the three arms.“The physicians did not follow protocol for various reasons, mainly reluctance to intensify therapy based on shared decision making,” they wrote.
Another limitation was the small sample size, which the investigators said could obscure differences between groups that in a larger population might have become clear.
“Long-term follow-up of the BEST for Kids cohort, including radiology results, is initiated to investigate possible lasting positive results of treatment to target in JIA,” they said.
SOURCE: Hissink Muller P et al. Ann Rheum Dis. Oct 12. doi: 10.1136/annrheumdis-2018-213902.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: Drug-free inactive disease is a feasible goal in the treatment of children with JIA.
Major finding: After 24 months of treatment to target aimed at achieving drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months), and 39% were drug free.
Study details: A randomized, single-blinded study that assessed three treatment strategies in 94 patients with JIA who were DMARD naive.
Disclosures: The study was investigator initiated but received financial support from Pfizer. No competing interests were declared by the authors.
Source: Hissink Muller P et al. Ann Rheum Dis. 2018 Oct 12. doi: 10.1136/annrheumdis-2018-213902.
Low BMD and spinal syndesmophytes predict radiographic progression in axSpA
Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.
The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”
In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.
They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.
Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.
At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).
In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.
The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.
“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.
The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.
“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.
“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.
They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.
SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.
Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.
The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”
In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.
They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.
Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.
At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).
In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.
The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.
“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.
The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.
“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.
“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.
They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.
SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.
Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.
The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”
In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.
They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.
Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.
At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).
In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.
The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.
“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.
The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.
“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.
“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.
They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.
SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.
FROM ARTHRITIS RESEARCH & THERAPY
Key clinical point: Low bone mineral density and existing spinal syndesmophytes are risk factors for new syndesmophytes and radiographic progression in people with axial spondyloarthritis.
Major finding: The presence of syndesmophytes at baseline and low BMD were predictors of new syndesmophytes over the following 2 years (OR, 5.5; 95% CI, 2.0-15.2 and OR, 3.6; 95% CI, 1.1-11.8, respectively).
Study details: A longitudinal observational study of 119 consecutive patients with axial SpA aged under 50 years who fulfilled the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria.
Disclosures: No specific funding was received from any public, commercial or not-for-profit bodies. No authors declared any conflicts of interest.
Source: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.
Inflammatory arthritis a common rheumatic adverse event with ICIs
Inflammatory arthritis (IA) is the most common rheumatic adverse event seen in people on immune checkpoint inhibitor (ICI) therapy and can largely be managed by rheumatologists without the need to halt cancer treatment, according to Michael D. Richter, MD, of the Mayo School of Graduate Medical Education, Rochester, Minn., and his colleagues.
The investigators’ observations of patients seen at the Mayo Clinic over a 7-year period suggested that “IA should not be seen as a contraindication to continuing or restarting ICIs, ” although continuing ICI therapy concurrently with high-dose steroids is “generally not recommended.” Previous estimates of rheumatic adverse events with ICIs had ranged from 1% to 10%, and management had largely been based on the experience of experts and findings from retrospective studies, they noted.
“This study aims to add granularity to the existing literature by describing the prevalence, clinical characteristics, and treatment outcomes of a large, single-institution cohort of patients with rheumatic immune-related adverse events,” Dr. Richter and his associates wrote in an article published in Arthritis & Rheumatology.
The analysis included 1,293 patients who had received treatment with any ICI at the Mayo Clinic between January 2011 and March 2018. Patients who had received treatment at other centers but were seen at the Mayo clinic for their rheumatic adverse event were also included.
Overall, 61 patients experienced a rheumatic immune-related adverse event (Rh-irAE) related to checkpoint inhibitor treatment; 43 were from the Mayo cohort and 18 were from other centers. The average age of the patients was 62.6 years, and almost half (49%) were female.
New-onset inflammatory arthritis was the most common Rh-irAE reported (n = 34), with the majority of patients presenting with polyarticular symptoms (n = 22; 65%).
Most of these patients were managed by a rheumatologist and were treated with systemic glucocorticoids (n = 26; 76%) for an average duration of 18 weeks. Five of the patients also required disease-modifying antirheumatic drugs and eight needed NSAIDS or intra-articular steroids.
The investigators noted that almost half of the patients (47%) experienced a complete resolution of symptoms during the study period, although few achieved this while they were still on the cancer treatment.
According to the investigators, the clinical characteristics of IA in their cohort support the existing literature: “Time of symptom onset is generally 4-8 weeks after starting ICI therapy. … The majority of patients require long courses of systemic glucocorticoids. And very few achieve complete symptom resolution while continuing ICI therapy,” they wrote.
The database analysis also revealed that a further 10 patients developed myopathy, with all patients presenting with myalgias and weaknesses. Five had bulbar myopathy, and four patients were diagnosed with concomitant myocarditis. All of these patients were treated with glucocorticoids for an average treatment duration of 15 weeks.
Complete resolution of the myopathy was observed in 70%, but two patients died from complications related to myocarditis and bulbar myopathy.
Other rheumatic events included four cases of vasculitis and four cases of polymyalgia rheumatica and six cases of diffuse systemic sclerosis or sicca syndromes.
“In lieu of controlled prospective studies, this cohort may serve as a guide for rheumatologists managing and counseling patients with Rh-IrAEs,” the investigators concluded.
“It remains unclear why some patients develop Rh-irAEs, and so far no genomic risk factors have been identified, though the varied clinical phenotypes of Rh-irAEs certainly suggest multiple underlying immunopathogenic mechanisms. Further prospective studies that distinguish between subsets of Rh-irAEs are necessary to better understand their pathophysiology and improve clinical care,” they added.
They noted that a limitation of the study was its reliance on retrospective data and clinician diagnoses.
None of the authors declared any financial or other conflicts of interest.
SOURCE: Richter MD et al. Arthritis Rheumatol. 2018 Oct 3. doi: 10.1002/art.40745.
Inflammatory arthritis (IA) is the most common rheumatic adverse event seen in people on immune checkpoint inhibitor (ICI) therapy and can largely be managed by rheumatologists without the need to halt cancer treatment, according to Michael D. Richter, MD, of the Mayo School of Graduate Medical Education, Rochester, Minn., and his colleagues.
The investigators’ observations of patients seen at the Mayo Clinic over a 7-year period suggested that “IA should not be seen as a contraindication to continuing or restarting ICIs, ” although continuing ICI therapy concurrently with high-dose steroids is “generally not recommended.” Previous estimates of rheumatic adverse events with ICIs had ranged from 1% to 10%, and management had largely been based on the experience of experts and findings from retrospective studies, they noted.
“This study aims to add granularity to the existing literature by describing the prevalence, clinical characteristics, and treatment outcomes of a large, single-institution cohort of patients with rheumatic immune-related adverse events,” Dr. Richter and his associates wrote in an article published in Arthritis & Rheumatology.
The analysis included 1,293 patients who had received treatment with any ICI at the Mayo Clinic between January 2011 and March 2018. Patients who had received treatment at other centers but were seen at the Mayo clinic for their rheumatic adverse event were also included.
Overall, 61 patients experienced a rheumatic immune-related adverse event (Rh-irAE) related to checkpoint inhibitor treatment; 43 were from the Mayo cohort and 18 were from other centers. The average age of the patients was 62.6 years, and almost half (49%) were female.
New-onset inflammatory arthritis was the most common Rh-irAE reported (n = 34), with the majority of patients presenting with polyarticular symptoms (n = 22; 65%).
Most of these patients were managed by a rheumatologist and were treated with systemic glucocorticoids (n = 26; 76%) for an average duration of 18 weeks. Five of the patients also required disease-modifying antirheumatic drugs and eight needed NSAIDS or intra-articular steroids.
The investigators noted that almost half of the patients (47%) experienced a complete resolution of symptoms during the study period, although few achieved this while they were still on the cancer treatment.
According to the investigators, the clinical characteristics of IA in their cohort support the existing literature: “Time of symptom onset is generally 4-8 weeks after starting ICI therapy. … The majority of patients require long courses of systemic glucocorticoids. And very few achieve complete symptom resolution while continuing ICI therapy,” they wrote.
The database analysis also revealed that a further 10 patients developed myopathy, with all patients presenting with myalgias and weaknesses. Five had bulbar myopathy, and four patients were diagnosed with concomitant myocarditis. All of these patients were treated with glucocorticoids for an average treatment duration of 15 weeks.
Complete resolution of the myopathy was observed in 70%, but two patients died from complications related to myocarditis and bulbar myopathy.
Other rheumatic events included four cases of vasculitis and four cases of polymyalgia rheumatica and six cases of diffuse systemic sclerosis or sicca syndromes.
“In lieu of controlled prospective studies, this cohort may serve as a guide for rheumatologists managing and counseling patients with Rh-IrAEs,” the investigators concluded.
“It remains unclear why some patients develop Rh-irAEs, and so far no genomic risk factors have been identified, though the varied clinical phenotypes of Rh-irAEs certainly suggest multiple underlying immunopathogenic mechanisms. Further prospective studies that distinguish between subsets of Rh-irAEs are necessary to better understand their pathophysiology and improve clinical care,” they added.
They noted that a limitation of the study was its reliance on retrospective data and clinician diagnoses.
None of the authors declared any financial or other conflicts of interest.
SOURCE: Richter MD et al. Arthritis Rheumatol. 2018 Oct 3. doi: 10.1002/art.40745.
Inflammatory arthritis (IA) is the most common rheumatic adverse event seen in people on immune checkpoint inhibitor (ICI) therapy and can largely be managed by rheumatologists without the need to halt cancer treatment, according to Michael D. Richter, MD, of the Mayo School of Graduate Medical Education, Rochester, Minn., and his colleagues.
The investigators’ observations of patients seen at the Mayo Clinic over a 7-year period suggested that “IA should not be seen as a contraindication to continuing or restarting ICIs, ” although continuing ICI therapy concurrently with high-dose steroids is “generally not recommended.” Previous estimates of rheumatic adverse events with ICIs had ranged from 1% to 10%, and management had largely been based on the experience of experts and findings from retrospective studies, they noted.
“This study aims to add granularity to the existing literature by describing the prevalence, clinical characteristics, and treatment outcomes of a large, single-institution cohort of patients with rheumatic immune-related adverse events,” Dr. Richter and his associates wrote in an article published in Arthritis & Rheumatology.
The analysis included 1,293 patients who had received treatment with any ICI at the Mayo Clinic between January 2011 and March 2018. Patients who had received treatment at other centers but were seen at the Mayo clinic for their rheumatic adverse event were also included.
Overall, 61 patients experienced a rheumatic immune-related adverse event (Rh-irAE) related to checkpoint inhibitor treatment; 43 were from the Mayo cohort and 18 were from other centers. The average age of the patients was 62.6 years, and almost half (49%) were female.
New-onset inflammatory arthritis was the most common Rh-irAE reported (n = 34), with the majority of patients presenting with polyarticular symptoms (n = 22; 65%).
Most of these patients were managed by a rheumatologist and were treated with systemic glucocorticoids (n = 26; 76%) for an average duration of 18 weeks. Five of the patients also required disease-modifying antirheumatic drugs and eight needed NSAIDS or intra-articular steroids.
The investigators noted that almost half of the patients (47%) experienced a complete resolution of symptoms during the study period, although few achieved this while they were still on the cancer treatment.
According to the investigators, the clinical characteristics of IA in their cohort support the existing literature: “Time of symptom onset is generally 4-8 weeks after starting ICI therapy. … The majority of patients require long courses of systemic glucocorticoids. And very few achieve complete symptom resolution while continuing ICI therapy,” they wrote.
The database analysis also revealed that a further 10 patients developed myopathy, with all patients presenting with myalgias and weaknesses. Five had bulbar myopathy, and four patients were diagnosed with concomitant myocarditis. All of these patients were treated with glucocorticoids for an average treatment duration of 15 weeks.
Complete resolution of the myopathy was observed in 70%, but two patients died from complications related to myocarditis and bulbar myopathy.
Other rheumatic events included four cases of vasculitis and four cases of polymyalgia rheumatica and six cases of diffuse systemic sclerosis or sicca syndromes.
“In lieu of controlled prospective studies, this cohort may serve as a guide for rheumatologists managing and counseling patients with Rh-IrAEs,” the investigators concluded.
“It remains unclear why some patients develop Rh-irAEs, and so far no genomic risk factors have been identified, though the varied clinical phenotypes of Rh-irAEs certainly suggest multiple underlying immunopathogenic mechanisms. Further prospective studies that distinguish between subsets of Rh-irAEs are necessary to better understand their pathophysiology and improve clinical care,” they added.
They noted that a limitation of the study was its reliance on retrospective data and clinician diagnoses.
None of the authors declared any financial or other conflicts of interest.
SOURCE: Richter MD et al. Arthritis Rheumatol. 2018 Oct 3. doi: 10.1002/art.40745.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Inflammatory arthritis (IA) is the most common form of rheumatic immune-related adverse event (Rh-irAE) related to ICI treatment. The majority of patients with an Rh-irAE (90% in the current cohort) remained on ICI treatment, which suggests that IA should not be seen as a contraindication to continuing or restarting ICI treatment.
Major finding: Among a cohort of 1,293 patients and 18 patients who received ICI therapy at other centers, 61 cases of Rh-irAE were identified. Over half (n = 34) of these patients presented with IA.
Study details: A retrospective analysis of a database of all patients who received any ICI at the Mayo Clinic between January 2011 and March 2018.
Disclosures: None of the authors declared any financial or other conflicts of interest.
Source: Richter MD et al. Arthritis Rheumatol. 2018 Oct 3. doi: 10.1002/art.40745.
Suicide risk doubled in COPD patients taking benzodiazepines
Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.
The risk of all-cause mortality in , according to the results of research published in the Annals of the American Thoracic Society.
Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.
However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.
They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.
“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.
In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.
Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).
With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).
Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.
Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”
According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.
They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).
“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.
The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).
The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.
Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).
The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.
However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.
“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.
The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.
SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.
Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.
The risk of all-cause mortality in , according to the results of research published in the Annals of the American Thoracic Society.
Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.
However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.
They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.
“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.
In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.
Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).
With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).
Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.
Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”
According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.
They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).
“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.
The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).
The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.
Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).
The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.
However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.
“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.
The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.
SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.
Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.
The risk of all-cause mortality in , according to the results of research published in the Annals of the American Thoracic Society.
Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.
However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.
They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.
“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.
In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.
Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).
With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).
Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.
Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”
According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.
They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).
“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.
The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).
The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.
Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).
The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.
However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.
“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.
The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.
SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.
FROM ANNALS OF THE AMERICAN THORACIC SOCIETY
Key clinical point: Health care providers should consider discontinuing benzodiazepines among COPD patients already at high suicide risk and should avoid concomitant opioid use.
Major finding: A strong risk of suicide was associated with benzodiazepine use among patients with COPD (HR, 2.33; 95% CI, 1.14-4.79).
Study details: A nationwide cohort of patients with comorbid COPD and PTSD identified from Veteran’s Health Administration administrative data between 2010 and 2012.
Disclosures: The study was funded by several National Institutes of Health grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.
Source: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.
Delayed pushing during labor does not benefit mother or baby, study finds
according to the results of a randomized trial.
“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”
They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.
The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.
Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).
The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).
In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.
Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.
“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”
They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.
The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.
SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.
Of the almost 4 million births in the United States each year, 68% are vaginal deliveries, which illustrates how important it is to have additional evidence to guide the management of labor, Jeffrey D. Sperling, MD, and Dana R. Gossett, MD, wrote in an accompanying editorial. They noted that, despite a lack of blinding and other limitations, as well as the fact there is no one risk-free solution regarding labor management or route of delivery, the results of this study have improved the understanding “of the risks and benefits of different strategies of labor management.”
The study, they added, “presents the only contemporary level 1 evidence available on the topic of whether the timing of pushing in the second stage of labor can have an effect on outcomes.”
The data “contribute to a growing body of literature on how to optimally manage labor in an evidenced-based fashion and improve perinatal outcomes without compromising maternal satisfaction,” they wrote. They recommended that future research should include exploring the effects and outcomes of delaying pushing among multiparous women, women with a previous cesarean delivery, and women who have not received epidural analgesia.
Dr. Sperling and Dr. Gossett are with the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. Dr. Gossett reported serving as a consultant to Bayer Pharmaceuticals. No other disclosures were reported (JAMA. 2018;320[14]:1439-40).
Of the almost 4 million births in the United States each year, 68% are vaginal deliveries, which illustrates how important it is to have additional evidence to guide the management of labor, Jeffrey D. Sperling, MD, and Dana R. Gossett, MD, wrote in an accompanying editorial. They noted that, despite a lack of blinding and other limitations, as well as the fact there is no one risk-free solution regarding labor management or route of delivery, the results of this study have improved the understanding “of the risks and benefits of different strategies of labor management.”
The study, they added, “presents the only contemporary level 1 evidence available on the topic of whether the timing of pushing in the second stage of labor can have an effect on outcomes.”
The data “contribute to a growing body of literature on how to optimally manage labor in an evidenced-based fashion and improve perinatal outcomes without compromising maternal satisfaction,” they wrote. They recommended that future research should include exploring the effects and outcomes of delaying pushing among multiparous women, women with a previous cesarean delivery, and women who have not received epidural analgesia.
Dr. Sperling and Dr. Gossett are with the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. Dr. Gossett reported serving as a consultant to Bayer Pharmaceuticals. No other disclosures were reported (JAMA. 2018;320[14]:1439-40).
Of the almost 4 million births in the United States each year, 68% are vaginal deliveries, which illustrates how important it is to have additional evidence to guide the management of labor, Jeffrey D. Sperling, MD, and Dana R. Gossett, MD, wrote in an accompanying editorial. They noted that, despite a lack of blinding and other limitations, as well as the fact there is no one risk-free solution regarding labor management or route of delivery, the results of this study have improved the understanding “of the risks and benefits of different strategies of labor management.”
The study, they added, “presents the only contemporary level 1 evidence available on the topic of whether the timing of pushing in the second stage of labor can have an effect on outcomes.”
The data “contribute to a growing body of literature on how to optimally manage labor in an evidenced-based fashion and improve perinatal outcomes without compromising maternal satisfaction,” they wrote. They recommended that future research should include exploring the effects and outcomes of delaying pushing among multiparous women, women with a previous cesarean delivery, and women who have not received epidural analgesia.
Dr. Sperling and Dr. Gossett are with the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. Dr. Gossett reported serving as a consultant to Bayer Pharmaceuticals. No other disclosures were reported (JAMA. 2018;320[14]:1439-40).
according to the results of a randomized trial.
“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”
They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.
The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.
Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).
The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).
In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.
Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.
“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”
They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.
The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.
SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.
according to the results of a randomized trial.
“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”
They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.
The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.
Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).
The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).
In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.
Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.
“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”
They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.
The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.
SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.
FROM JAMA
Key clinical point: Delayed pushing during the second stage of labor may not reduce the risk of cesarean delivery and may lengthen the duration of labor.
Major finding: The rate of spontaneous vaginal delivery did not differ between groups (85.9% in the immediate pushing group versus 86.5% in the delayed pushing group).
Study details: A multicenter trial involving 2,414 nulliparous women receiving neuraxial analgesia, who were randomized to immediate pushing or delayed pushing during the second stage of labor.
Disclosures: The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.
Source: Cahill AG et al. JAMA. 2018;320(14):1444-54.
Anti-RNPC3 antibody positive status linked to GI dysmotility in systemic sclerosis
in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.
GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.
Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.
In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.
Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.
Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.
Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).
Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.
“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.
This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).
Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).
Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).
However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).
Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.
They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).
“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.
“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.
The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763
This study represents good work in confirming the association of anti-RNPC3 positivity with severe GI disease first noted by Johns Hopkins investigators in a single-center study (Arthritis Rheumatol. 2017 Jun; 69[6]:1306-12). Now that Dr. McMahan and her associates have confirmed this association in the most severe of GI problems in SSc, it would be very useful to see if there is a lesser degree of GI involvement that also correlates (for example, using the validated UCLA Gastrointestinal Tract Questionnaire 2.0, which gives a continuous graded response).
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also in part-time practice in Los Angeles and Seattle.
This study represents good work in confirming the association of anti-RNPC3 positivity with severe GI disease first noted by Johns Hopkins investigators in a single-center study (Arthritis Rheumatol. 2017 Jun; 69[6]:1306-12). Now that Dr. McMahan and her associates have confirmed this association in the most severe of GI problems in SSc, it would be very useful to see if there is a lesser degree of GI involvement that also correlates (for example, using the validated UCLA Gastrointestinal Tract Questionnaire 2.0, which gives a continuous graded response).
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also in part-time practice in Los Angeles and Seattle.
This study represents good work in confirming the association of anti-RNPC3 positivity with severe GI disease first noted by Johns Hopkins investigators in a single-center study (Arthritis Rheumatol. 2017 Jun; 69[6]:1306-12). Now that Dr. McMahan and her associates have confirmed this association in the most severe of GI problems in SSc, it would be very useful to see if there is a lesser degree of GI involvement that also correlates (for example, using the validated UCLA Gastrointestinal Tract Questionnaire 2.0, which gives a continuous graded response).
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also in part-time practice in Los Angeles and Seattle.
in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.
GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.
Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.
In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.
Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.
Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.
Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).
Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.
“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.
This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).
Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).
Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).
However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).
Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.
They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).
“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.
“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.
The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763
in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.
GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.
Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.
In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.
Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.
Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.
Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).
Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.
“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.
This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).
Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).
Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).
However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).
Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.
They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).
“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.
“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.
The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Antibody status may inform GI risk stratification in people with systemic sclerosis.
Major finding: Anti-RNPC3 antibody positive SSc patients are significantly more likely to have moderate to severe GI dysfunction. In a fully adjusted model, patients with moderate to severe GI disease had 3.8-fold higher odds of having anti-RNPC3 antibodies.
Study details: A comparison of anti-RNPC3 antibodies in a discovery cohort of SSc patients with severe GI dysfunction who were on total parenteral nutrition compared with asymptomatic patients from the Johns Hopkins Scleroderma Center. Followed by a case control study to confirm the findings using the Pittsburgh Scleroderma cohort.
Disclosures: The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.
Source: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763.
Swings in four metabolic measures predicted death in healthy people
, based on data from a 5.5-year population-based study in Korea.
In a model adjusted for age, sex, smoking, alcohol consumption, regular exercise, and income status the group with high variability for all four parameters had a significantly higher risk for all-cause mortality (hazard ratio, 2.27; 95% confidence interval, 2.13-2.42), for MI (HR, 1.43; 95% CI, 1.25-1.64), and for stroke (HR, 1.41; 95% CI, 1.25-1.60), compared with the group with low variability for all four parameters. The association with risk was graded and persisted after multivariable adjustment.
“Variability in metabolic parameters may be prognostic surrogate markers for predicting mortality and cardiovascular outcomes,” wrote senior author Seung-Hwan Lee, MD, PhD, and professor of endocrinology at the College of Medicine of the Catholic University of Korea in Seoul, South Korea, and colleagues. “High variability in metabolic parameters (may be) associated with adverse health outcomes not only in a diseased population, but also in the relatively healthy population although the mechanism could be somewhat different.”
Korea has a single-payer system, the Korean National Health Insurance system, that includes health information on its entire population. The researchers selected data from 6,748,773 people who were free of diabetes mellitus, hypertension, and dyslipidemia, and who underwent three or more health examinations during 2005-2012 that documented body mass index (BMI), fasting blood glucose, systolic blood pressure, and total cholesterol. Participants were followed to the end of 2015, for a median follow-up of 5.5 years. There were 54,785 deaths (0.8%), 22,498 cases of stroke (0.3%), and 21,452 MIs (0.3%).
The research team defined high variability as the highest quartile, classifying participants according to the number of high-variability parameters. A score of 4 indicated high variability in all four metabolic parameters – body weight, systolic blood pressure, total cholesterol, and fasting blood glucose.
In the highest quartile in fasting blood glucose variability, compared with the lowest quartile, the risk of all-cause mortality increased by 20% (HR, 1.20; 95% CI, 1.18-1.23), MI by 16% (HR, 1.16; 95% CI, 1.12-1.21), and stroke by 13% (HR, 1.13; 95% CI, 1.09-1.17).
For the highest quartile in total cholesterol variability, compared with the lowest quartile, the risk of all-cause mortality increased by 31% (HR, 1.31; 95% CI, 1.28-1.34), MI by 10% (HR, 1.10; 95% CI, 1.06-1.14), and stroke by 6% (HR, 1.06; 95% CI, 1.03-1.10).
For the highest quartile in systolic BP variability, compared with the lowest quartile, the risk of all-cause mortality increased by 19% (HR, 1.19; 95% CI, 1.16-1.22), MI by 7% (HR, 1.07; 95% CI, 1.03-1.11), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).
For the highest quartile in BMI variability, compared with the lowest quartile, the risk of all-cause mortality increased by 53% (HR, 1.53; 95% CI, 1.50-1.57), MI by 14% (HR, 1.14; 95% CI, 1.09-1.18), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).
“It is not certain whether these results from Korea would apply to the United States. However, several previous studies on variability were performed in other populations, suggesting that it is likely to be a common phenomenon,” the authors wrote.
The study was supported in part by the National Research Foundation of Korea Grant funded by the Korean Government. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
SOURCE: Lee S-H et al. Circulation. 2018 Oct.
, based on data from a 5.5-year population-based study in Korea.
In a model adjusted for age, sex, smoking, alcohol consumption, regular exercise, and income status the group with high variability for all four parameters had a significantly higher risk for all-cause mortality (hazard ratio, 2.27; 95% confidence interval, 2.13-2.42), for MI (HR, 1.43; 95% CI, 1.25-1.64), and for stroke (HR, 1.41; 95% CI, 1.25-1.60), compared with the group with low variability for all four parameters. The association with risk was graded and persisted after multivariable adjustment.
“Variability in metabolic parameters may be prognostic surrogate markers for predicting mortality and cardiovascular outcomes,” wrote senior author Seung-Hwan Lee, MD, PhD, and professor of endocrinology at the College of Medicine of the Catholic University of Korea in Seoul, South Korea, and colleagues. “High variability in metabolic parameters (may be) associated with adverse health outcomes not only in a diseased population, but also in the relatively healthy population although the mechanism could be somewhat different.”
Korea has a single-payer system, the Korean National Health Insurance system, that includes health information on its entire population. The researchers selected data from 6,748,773 people who were free of diabetes mellitus, hypertension, and dyslipidemia, and who underwent three or more health examinations during 2005-2012 that documented body mass index (BMI), fasting blood glucose, systolic blood pressure, and total cholesterol. Participants were followed to the end of 2015, for a median follow-up of 5.5 years. There were 54,785 deaths (0.8%), 22,498 cases of stroke (0.3%), and 21,452 MIs (0.3%).
The research team defined high variability as the highest quartile, classifying participants according to the number of high-variability parameters. A score of 4 indicated high variability in all four metabolic parameters – body weight, systolic blood pressure, total cholesterol, and fasting blood glucose.
In the highest quartile in fasting blood glucose variability, compared with the lowest quartile, the risk of all-cause mortality increased by 20% (HR, 1.20; 95% CI, 1.18-1.23), MI by 16% (HR, 1.16; 95% CI, 1.12-1.21), and stroke by 13% (HR, 1.13; 95% CI, 1.09-1.17).
For the highest quartile in total cholesterol variability, compared with the lowest quartile, the risk of all-cause mortality increased by 31% (HR, 1.31; 95% CI, 1.28-1.34), MI by 10% (HR, 1.10; 95% CI, 1.06-1.14), and stroke by 6% (HR, 1.06; 95% CI, 1.03-1.10).
For the highest quartile in systolic BP variability, compared with the lowest quartile, the risk of all-cause mortality increased by 19% (HR, 1.19; 95% CI, 1.16-1.22), MI by 7% (HR, 1.07; 95% CI, 1.03-1.11), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).
For the highest quartile in BMI variability, compared with the lowest quartile, the risk of all-cause mortality increased by 53% (HR, 1.53; 95% CI, 1.50-1.57), MI by 14% (HR, 1.14; 95% CI, 1.09-1.18), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).
“It is not certain whether these results from Korea would apply to the United States. However, several previous studies on variability were performed in other populations, suggesting that it is likely to be a common phenomenon,” the authors wrote.
The study was supported in part by the National Research Foundation of Korea Grant funded by the Korean Government. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
SOURCE: Lee S-H et al. Circulation. 2018 Oct.
, based on data from a 5.5-year population-based study in Korea.
In a model adjusted for age, sex, smoking, alcohol consumption, regular exercise, and income status the group with high variability for all four parameters had a significantly higher risk for all-cause mortality (hazard ratio, 2.27; 95% confidence interval, 2.13-2.42), for MI (HR, 1.43; 95% CI, 1.25-1.64), and for stroke (HR, 1.41; 95% CI, 1.25-1.60), compared with the group with low variability for all four parameters. The association with risk was graded and persisted after multivariable adjustment.
“Variability in metabolic parameters may be prognostic surrogate markers for predicting mortality and cardiovascular outcomes,” wrote senior author Seung-Hwan Lee, MD, PhD, and professor of endocrinology at the College of Medicine of the Catholic University of Korea in Seoul, South Korea, and colleagues. “High variability in metabolic parameters (may be) associated with adverse health outcomes not only in a diseased population, but also in the relatively healthy population although the mechanism could be somewhat different.”
Korea has a single-payer system, the Korean National Health Insurance system, that includes health information on its entire population. The researchers selected data from 6,748,773 people who were free of diabetes mellitus, hypertension, and dyslipidemia, and who underwent three or more health examinations during 2005-2012 that documented body mass index (BMI), fasting blood glucose, systolic blood pressure, and total cholesterol. Participants were followed to the end of 2015, for a median follow-up of 5.5 years. There were 54,785 deaths (0.8%), 22,498 cases of stroke (0.3%), and 21,452 MIs (0.3%).
The research team defined high variability as the highest quartile, classifying participants according to the number of high-variability parameters. A score of 4 indicated high variability in all four metabolic parameters – body weight, systolic blood pressure, total cholesterol, and fasting blood glucose.
In the highest quartile in fasting blood glucose variability, compared with the lowest quartile, the risk of all-cause mortality increased by 20% (HR, 1.20; 95% CI, 1.18-1.23), MI by 16% (HR, 1.16; 95% CI, 1.12-1.21), and stroke by 13% (HR, 1.13; 95% CI, 1.09-1.17).
For the highest quartile in total cholesterol variability, compared with the lowest quartile, the risk of all-cause mortality increased by 31% (HR, 1.31; 95% CI, 1.28-1.34), MI by 10% (HR, 1.10; 95% CI, 1.06-1.14), and stroke by 6% (HR, 1.06; 95% CI, 1.03-1.10).
For the highest quartile in systolic BP variability, compared with the lowest quartile, the risk of all-cause mortality increased by 19% (HR, 1.19; 95% CI, 1.16-1.22), MI by 7% (HR, 1.07; 95% CI, 1.03-1.11), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).
For the highest quartile in BMI variability, compared with the lowest quartile, the risk of all-cause mortality increased by 53% (HR, 1.53; 95% CI, 1.50-1.57), MI by 14% (HR, 1.14; 95% CI, 1.09-1.18), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).
“It is not certain whether these results from Korea would apply to the United States. However, several previous studies on variability were performed in other populations, suggesting that it is likely to be a common phenomenon,” the authors wrote.
The study was supported in part by the National Research Foundation of Korea Grant funded by the Korean Government. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
SOURCE: Lee S-H et al. Circulation. 2018 Oct.
FROM CIRCULATION
Key clinical point: Fluctuations in fasting glucose and cholesterol levels, systolic blood pressure, and body mass index are associated with a higher risk for all-cause mortality, myocardial infarction, and stroke in otherwise healthy people.
Major finding: The hazard ratios were 2.27 (95% CI, 2.13-2.42) for all-cause mortality, 1.43 (95% CI, 1.25-1.64) for MI, and 1.41 (95% CI, 1.25-1.60) for stroke.
Study details: An observational population-based study involving more than 6.7 million Koreans age 20 and older.
Disclosures: The study was funded by the National Research Foundation of Korea. The authors had no relevant conflicts of interest to declare.
Source: Lee S-H et al. Circulation. 2018 Oct.
Sulfasalazine pinpointed as reason for high triple-therapy discontinuation
Adverse events related to sulfasalazine played a role in the higher discontinuation rate observed for rheumatoid arthritis (RA) patients on triple therapy when compared with similar patients taking methotrexate and a tumor necrosis factor inhibitor in an observational cohort study of historical data during 2006-2012.
The findings shed some light on understanding if the noninferior efficacy of triple therapy (TT) with methotrexate (MTX), sulfasalazine (SSZ), and hydroxychloroquine (HCQ) in randomized trials versus combination MTX plus tumor necrosis factor inhibitor (MTX-TNFi) is matched by patients’ persistence and adherence to TT in real-world data.
“With the proven efficacy of these combination therapies, an understanding of the real-world observations outside of clinical trials should be investigated to determine if similar experiences are seen in clinical practice as in clinical trials,” first author Daniel P. Erhardt, MD, MPH, of the George E. Wahlen VA Medical Center, Salt Lake City, and his colleagues wrote in Arthritis Care & Research.
In the current study, the research team identified veterans with RA escalating treatment from MTX to MTX-TNFi (n = 2,125) or to triple therapy (n = 171) from Veterans Affairs (VA) clinical and administrative databases during 2006-2012.
Patients taking MTX-TNFi consistently had significantly higher levels of persistence than did TT patients regardless of the strictness of the definition used. The highest level of persistence as defined in the study – all medications (including MTX) filled without a 90-day or longer gap in treatment over the 12-month study period – was observed in 43.2% of the MTX-TNFi arm, compared with 17.6% in the TT arm. A more liberal definition of persistence that allowed discontinuation of any one disease-modifying antirheumatic drug (DMARD) in TT or MTX in the MTX-TNFi group – provided no new DMARDs were initiated – yielded a persistence rate of 50.3% for MTX-TNFi vs. 32.8% for the TT arm. The persistence rate for MTX-TNFi worsened somewhat to 42.9% when the same discontinuation was allowed and switching was permitted between drugs within the TNFi class for the MTX-TNFi combination group, but it stayed lower for the TT group at 33.9% when single DMARD discontinuation was allowed and switching between nonbiologic DMARDs was permitted (without a 90-day or longer gap prior to the switch).
Adherence as defined by 80% or more of days covered at 1 year was 25.3% in the MTX-TNFi arm, with individual adherence rates of 44.3% for MTX and 46% for TNFi. In comparison, adherence for TT overall was 10.5%, with adherence rates of 48.6% for MTX, 32.8% for HCQ, and 18.7% for SSZ.
TT group patients most commonly discontinued sulfasalazine (20.9%), followed by MTX (8.7%) and HCQ (7.8%), whereas in those treated with MTX-TNFi, many more stopped TNFi alone (53.9%) than MTX alone (19.1%). It also was more common to stop SSZ and HCQ together (37.4%) or all TT drugs (23.5%) than it was to stop MTX plus HCQ together (1.7%).
The most common reason for discontinuation in both groups was an adverse drug event (ADE), cited as the reason in 43.5% of TT patients and 35.7% of combination-therapy patients. Most SSZ discontinuations were reported as an ADE, most often because of concerns of GI toxicity or symptoms, the researchers said. GI toxicity or symptoms was cited as a reason for discontinuing for 18.3% of TT patients who discontinued, compared with only 1.7% of MTX-TNFi patients.
“Findings from our study indicate that ADE play a significant role in influencing drug discontinuation, and further efforts should focus on ways to mitigate ADE when initiating or escalating drug regimens for RA,” they concluded.
They noted that a large percentage of subjects who discontinued their combination therapy for RA were lost to follow-up from the VA system: 34.8% in the TT group and 32.2% in the MTX-TNFi group.
“Research should continue to focus on ascertaining methods to improve real-world treatment retention rates,” they advised.
“More research is also warranted to determine whether patient factors that influence medication adherence independently affect the likelihood of achieving clinical remission, regardless of which therapy is chosen for the treatment of their RA,” they added.
The research was supported by Specialty Care Center of Innovation in the Veterans Health Administration and by the Health Services Research and Development division of the Department of Veterans Affairs. Several of the authors reported receiving research funding and grants from several pharmaceutical companies.
SOURCE: Erhardt DP et al. Arthritis Care Res. 2018 Sep 17. doi: 10.1002/acr.23759
Adverse events related to sulfasalazine played a role in the higher discontinuation rate observed for rheumatoid arthritis (RA) patients on triple therapy when compared with similar patients taking methotrexate and a tumor necrosis factor inhibitor in an observational cohort study of historical data during 2006-2012.
The findings shed some light on understanding if the noninferior efficacy of triple therapy (TT) with methotrexate (MTX), sulfasalazine (SSZ), and hydroxychloroquine (HCQ) in randomized trials versus combination MTX plus tumor necrosis factor inhibitor (MTX-TNFi) is matched by patients’ persistence and adherence to TT in real-world data.
“With the proven efficacy of these combination therapies, an understanding of the real-world observations outside of clinical trials should be investigated to determine if similar experiences are seen in clinical practice as in clinical trials,” first author Daniel P. Erhardt, MD, MPH, of the George E. Wahlen VA Medical Center, Salt Lake City, and his colleagues wrote in Arthritis Care & Research.
In the current study, the research team identified veterans with RA escalating treatment from MTX to MTX-TNFi (n = 2,125) or to triple therapy (n = 171) from Veterans Affairs (VA) clinical and administrative databases during 2006-2012.
Patients taking MTX-TNFi consistently had significantly higher levels of persistence than did TT patients regardless of the strictness of the definition used. The highest level of persistence as defined in the study – all medications (including MTX) filled without a 90-day or longer gap in treatment over the 12-month study period – was observed in 43.2% of the MTX-TNFi arm, compared with 17.6% in the TT arm. A more liberal definition of persistence that allowed discontinuation of any one disease-modifying antirheumatic drug (DMARD) in TT or MTX in the MTX-TNFi group – provided no new DMARDs were initiated – yielded a persistence rate of 50.3% for MTX-TNFi vs. 32.8% for the TT arm. The persistence rate for MTX-TNFi worsened somewhat to 42.9% when the same discontinuation was allowed and switching was permitted between drugs within the TNFi class for the MTX-TNFi combination group, but it stayed lower for the TT group at 33.9% when single DMARD discontinuation was allowed and switching between nonbiologic DMARDs was permitted (without a 90-day or longer gap prior to the switch).
Adherence as defined by 80% or more of days covered at 1 year was 25.3% in the MTX-TNFi arm, with individual adherence rates of 44.3% for MTX and 46% for TNFi. In comparison, adherence for TT overall was 10.5%, with adherence rates of 48.6% for MTX, 32.8% for HCQ, and 18.7% for SSZ.
TT group patients most commonly discontinued sulfasalazine (20.9%), followed by MTX (8.7%) and HCQ (7.8%), whereas in those treated with MTX-TNFi, many more stopped TNFi alone (53.9%) than MTX alone (19.1%). It also was more common to stop SSZ and HCQ together (37.4%) or all TT drugs (23.5%) than it was to stop MTX plus HCQ together (1.7%).
The most common reason for discontinuation in both groups was an adverse drug event (ADE), cited as the reason in 43.5% of TT patients and 35.7% of combination-therapy patients. Most SSZ discontinuations were reported as an ADE, most often because of concerns of GI toxicity or symptoms, the researchers said. GI toxicity or symptoms was cited as a reason for discontinuing for 18.3% of TT patients who discontinued, compared with only 1.7% of MTX-TNFi patients.
“Findings from our study indicate that ADE play a significant role in influencing drug discontinuation, and further efforts should focus on ways to mitigate ADE when initiating or escalating drug regimens for RA,” they concluded.
They noted that a large percentage of subjects who discontinued their combination therapy for RA were lost to follow-up from the VA system: 34.8% in the TT group and 32.2% in the MTX-TNFi group.
“Research should continue to focus on ascertaining methods to improve real-world treatment retention rates,” they advised.
“More research is also warranted to determine whether patient factors that influence medication adherence independently affect the likelihood of achieving clinical remission, regardless of which therapy is chosen for the treatment of their RA,” they added.
The research was supported by Specialty Care Center of Innovation in the Veterans Health Administration and by the Health Services Research and Development division of the Department of Veterans Affairs. Several of the authors reported receiving research funding and grants from several pharmaceutical companies.
SOURCE: Erhardt DP et al. Arthritis Care Res. 2018 Sep 17. doi: 10.1002/acr.23759
Adverse events related to sulfasalazine played a role in the higher discontinuation rate observed for rheumatoid arthritis (RA) patients on triple therapy when compared with similar patients taking methotrexate and a tumor necrosis factor inhibitor in an observational cohort study of historical data during 2006-2012.
The findings shed some light on understanding if the noninferior efficacy of triple therapy (TT) with methotrexate (MTX), sulfasalazine (SSZ), and hydroxychloroquine (HCQ) in randomized trials versus combination MTX plus tumor necrosis factor inhibitor (MTX-TNFi) is matched by patients’ persistence and adherence to TT in real-world data.
“With the proven efficacy of these combination therapies, an understanding of the real-world observations outside of clinical trials should be investigated to determine if similar experiences are seen in clinical practice as in clinical trials,” first author Daniel P. Erhardt, MD, MPH, of the George E. Wahlen VA Medical Center, Salt Lake City, and his colleagues wrote in Arthritis Care & Research.
In the current study, the research team identified veterans with RA escalating treatment from MTX to MTX-TNFi (n = 2,125) or to triple therapy (n = 171) from Veterans Affairs (VA) clinical and administrative databases during 2006-2012.
Patients taking MTX-TNFi consistently had significantly higher levels of persistence than did TT patients regardless of the strictness of the definition used. The highest level of persistence as defined in the study – all medications (including MTX) filled without a 90-day or longer gap in treatment over the 12-month study period – was observed in 43.2% of the MTX-TNFi arm, compared with 17.6% in the TT arm. A more liberal definition of persistence that allowed discontinuation of any one disease-modifying antirheumatic drug (DMARD) in TT or MTX in the MTX-TNFi group – provided no new DMARDs were initiated – yielded a persistence rate of 50.3% for MTX-TNFi vs. 32.8% for the TT arm. The persistence rate for MTX-TNFi worsened somewhat to 42.9% when the same discontinuation was allowed and switching was permitted between drugs within the TNFi class for the MTX-TNFi combination group, but it stayed lower for the TT group at 33.9% when single DMARD discontinuation was allowed and switching between nonbiologic DMARDs was permitted (without a 90-day or longer gap prior to the switch).
Adherence as defined by 80% or more of days covered at 1 year was 25.3% in the MTX-TNFi arm, with individual adherence rates of 44.3% for MTX and 46% for TNFi. In comparison, adherence for TT overall was 10.5%, with adherence rates of 48.6% for MTX, 32.8% for HCQ, and 18.7% for SSZ.
TT group patients most commonly discontinued sulfasalazine (20.9%), followed by MTX (8.7%) and HCQ (7.8%), whereas in those treated with MTX-TNFi, many more stopped TNFi alone (53.9%) than MTX alone (19.1%). It also was more common to stop SSZ and HCQ together (37.4%) or all TT drugs (23.5%) than it was to stop MTX plus HCQ together (1.7%).
The most common reason for discontinuation in both groups was an adverse drug event (ADE), cited as the reason in 43.5% of TT patients and 35.7% of combination-therapy patients. Most SSZ discontinuations were reported as an ADE, most often because of concerns of GI toxicity or symptoms, the researchers said. GI toxicity or symptoms was cited as a reason for discontinuing for 18.3% of TT patients who discontinued, compared with only 1.7% of MTX-TNFi patients.
“Findings from our study indicate that ADE play a significant role in influencing drug discontinuation, and further efforts should focus on ways to mitigate ADE when initiating or escalating drug regimens for RA,” they concluded.
They noted that a large percentage of subjects who discontinued their combination therapy for RA were lost to follow-up from the VA system: 34.8% in the TT group and 32.2% in the MTX-TNFi group.
“Research should continue to focus on ascertaining methods to improve real-world treatment retention rates,” they advised.
“More research is also warranted to determine whether patient factors that influence medication adherence independently affect the likelihood of achieving clinical remission, regardless of which therapy is chosen for the treatment of their RA,” they added.
The research was supported by Specialty Care Center of Innovation in the Veterans Health Administration and by the Health Services Research and Development division of the Department of Veterans Affairs. Several of the authors reported receiving research funding and grants from several pharmaceutical companies.
SOURCE: Erhardt DP et al. Arthritis Care Res. 2018 Sep 17. doi: 10.1002/acr.23759
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Compared with RA patients on methotrexate and a TNF inhibitor, patients on triple therapy are more likely to discontinue treatment, largely because of adverse events with sulfasalazine (SSZ).
Major finding: Adherence was higher for the MTX-TNFi group (26%) than for the triple-therapy group (11%) (P less than .0001). The triple-therapy group was associated with significantly more treatment discontinuation, which was most often because of the adverse drug events from SSZ.
Study details: A retrospective observational cohort study using historical data from Veterans Affairs clinical and administrative databases during Jan. 1, 2006–Dec. 31, 2012.
Disclosures: The research was supported by Specialty Care Center of Innovation in the Veterans Health Administration and by the Health Services Research and Development division of the Department of Veterans Affairs. Several of the authors reported having received research funding and grants from several pharmaceutical companies.
Source: Erhardt DP et al. Arthritis Care Res. 2018 Sep 17. doi: 10.1002/acr.23759
Online diabetes prevention programs as good as face-to-face programs
, researchers report.
Writing in background information to their paper, Tannaz Moin, MD, an endocrinologist at the VA Greater Los Angeles Healthcare System and the Veterans Affairs’ Health Services Research and Development Center for the Study of Healthcare Innovation, Implementation, and Policy, and her associates, said intensive lifestyle interventions such as diabetes prevention programs (DPP) could lower the risk of incident diabetes by 58%, but a lack of reach significantly attenuated their population impact in real-world settings.
“Building evidence for online DPP is important because of its potential for increasing reach because most U.S. adults (87%) use the Internet,” they wrote in their paper, published in the American Journal of Preventive Medicine.
They therefore set out to compare weight loss results from 114 veterans taking part in the Veterans Administration’s face-to-face standard-of-care weight management program MOVE! with an online program involving 268 obese or overweight veterans with prediabetes and 273 people taking part in an in-person program.
MOVE! included 8-12 face-to-face healthy-lifestyle sessions and monthly maintenance sessions but with no specified goals. The online program involved virtual groups of participants: live e-coaches who monitored group interactions and provided the participants with feedback via phone and private online messages; weekly educational modules on healthy eating and exercise; and wireless scales to record participant weights.
The in-person program consisted of 8-22 group-based face-to-face sessions focused on 7% weight loss and at least 150 minutes per session of moderate physical activity.
Weight loss, considered by the authors to be a significant predictor of diabetes risk reduction, was recorded at 6 months and then again at 12 months in all three interventions.
An analysis of 242 participants enrolled in the intensive, multifaceted online DPP intervention (26 were excluded because they did not have more than two available weights) revealed a significant weight change of –4.7 kg at 6 months and –4 kg at 12 months’ follow-up. On average, these participants lost 3.7% of their baseline weight at 12 months.
At both times weight change (kg and percentage) was not significantly different between the online intervention and those taking part in the in-person DPP (–4.8 and –4.1 kg for online vs –4 kg and –3.9 kg in-person for those completing more than one module/session). Both groups also had higher weight loss (percentage and kg) at 6 and 12 months compared with MOVE! participants (–1.1kg and 0.10 kg).
The research team noted that the online program had better participation than did the in-person program, with 87% of online participants completing eight or more sessions, compared with 59% for the in-person program and 55% for MOVE!
They suggested this was because the online program had several user-friendly features that increased the frequency of potential “touches” participants received over time.
“Future studies examining how inline DPP intervention components can work together to impact participation and engagement are key,” they said.
“This is one of the first studies to report weight outcomes irrespective of the level of engagement with an online DPP intervention and to examine outcomes compared with in person DPP. Overall, these findings may have important implications for national efforts to disseminate DPP,” they concluded.
The authors conceded that the generalizability of their study was limited as it included veterans receiving care in the VHA.
SOURCE: Am J Prev Med. 2018 Sep 24. doi: 10.1016/j.amepre.2018.06.028
, researchers report.
Writing in background information to their paper, Tannaz Moin, MD, an endocrinologist at the VA Greater Los Angeles Healthcare System and the Veterans Affairs’ Health Services Research and Development Center for the Study of Healthcare Innovation, Implementation, and Policy, and her associates, said intensive lifestyle interventions such as diabetes prevention programs (DPP) could lower the risk of incident diabetes by 58%, but a lack of reach significantly attenuated their population impact in real-world settings.
“Building evidence for online DPP is important because of its potential for increasing reach because most U.S. adults (87%) use the Internet,” they wrote in their paper, published in the American Journal of Preventive Medicine.
They therefore set out to compare weight loss results from 114 veterans taking part in the Veterans Administration’s face-to-face standard-of-care weight management program MOVE! with an online program involving 268 obese or overweight veterans with prediabetes and 273 people taking part in an in-person program.
MOVE! included 8-12 face-to-face healthy-lifestyle sessions and monthly maintenance sessions but with no specified goals. The online program involved virtual groups of participants: live e-coaches who monitored group interactions and provided the participants with feedback via phone and private online messages; weekly educational modules on healthy eating and exercise; and wireless scales to record participant weights.
The in-person program consisted of 8-22 group-based face-to-face sessions focused on 7% weight loss and at least 150 minutes per session of moderate physical activity.
Weight loss, considered by the authors to be a significant predictor of diabetes risk reduction, was recorded at 6 months and then again at 12 months in all three interventions.
An analysis of 242 participants enrolled in the intensive, multifaceted online DPP intervention (26 were excluded because they did not have more than two available weights) revealed a significant weight change of –4.7 kg at 6 months and –4 kg at 12 months’ follow-up. On average, these participants lost 3.7% of their baseline weight at 12 months.
At both times weight change (kg and percentage) was not significantly different between the online intervention and those taking part in the in-person DPP (–4.8 and –4.1 kg for online vs –4 kg and –3.9 kg in-person for those completing more than one module/session). Both groups also had higher weight loss (percentage and kg) at 6 and 12 months compared with MOVE! participants (–1.1kg and 0.10 kg).
The research team noted that the online program had better participation than did the in-person program, with 87% of online participants completing eight or more sessions, compared with 59% for the in-person program and 55% for MOVE!
They suggested this was because the online program had several user-friendly features that increased the frequency of potential “touches” participants received over time.
“Future studies examining how inline DPP intervention components can work together to impact participation and engagement are key,” they said.
“This is one of the first studies to report weight outcomes irrespective of the level of engagement with an online DPP intervention and to examine outcomes compared with in person DPP. Overall, these findings may have important implications for national efforts to disseminate DPP,” they concluded.
The authors conceded that the generalizability of their study was limited as it included veterans receiving care in the VHA.
SOURCE: Am J Prev Med. 2018 Sep 24. doi: 10.1016/j.amepre.2018.06.028
, researchers report.
Writing in background information to their paper, Tannaz Moin, MD, an endocrinologist at the VA Greater Los Angeles Healthcare System and the Veterans Affairs’ Health Services Research and Development Center for the Study of Healthcare Innovation, Implementation, and Policy, and her associates, said intensive lifestyle interventions such as diabetes prevention programs (DPP) could lower the risk of incident diabetes by 58%, but a lack of reach significantly attenuated their population impact in real-world settings.
“Building evidence for online DPP is important because of its potential for increasing reach because most U.S. adults (87%) use the Internet,” they wrote in their paper, published in the American Journal of Preventive Medicine.
They therefore set out to compare weight loss results from 114 veterans taking part in the Veterans Administration’s face-to-face standard-of-care weight management program MOVE! with an online program involving 268 obese or overweight veterans with prediabetes and 273 people taking part in an in-person program.
MOVE! included 8-12 face-to-face healthy-lifestyle sessions and monthly maintenance sessions but with no specified goals. The online program involved virtual groups of participants: live e-coaches who monitored group interactions and provided the participants with feedback via phone and private online messages; weekly educational modules on healthy eating and exercise; and wireless scales to record participant weights.
The in-person program consisted of 8-22 group-based face-to-face sessions focused on 7% weight loss and at least 150 minutes per session of moderate physical activity.
Weight loss, considered by the authors to be a significant predictor of diabetes risk reduction, was recorded at 6 months and then again at 12 months in all three interventions.
An analysis of 242 participants enrolled in the intensive, multifaceted online DPP intervention (26 were excluded because they did not have more than two available weights) revealed a significant weight change of –4.7 kg at 6 months and –4 kg at 12 months’ follow-up. On average, these participants lost 3.7% of their baseline weight at 12 months.
At both times weight change (kg and percentage) was not significantly different between the online intervention and those taking part in the in-person DPP (–4.8 and –4.1 kg for online vs –4 kg and –3.9 kg in-person for those completing more than one module/session). Both groups also had higher weight loss (percentage and kg) at 6 and 12 months compared with MOVE! participants (–1.1kg and 0.10 kg).
The research team noted that the online program had better participation than did the in-person program, with 87% of online participants completing eight or more sessions, compared with 59% for the in-person program and 55% for MOVE!
They suggested this was because the online program had several user-friendly features that increased the frequency of potential “touches” participants received over time.
“Future studies examining how inline DPP intervention components can work together to impact participation and engagement are key,” they said.
“This is one of the first studies to report weight outcomes irrespective of the level of engagement with an online DPP intervention and to examine outcomes compared with in person DPP. Overall, these findings may have important implications for national efforts to disseminate DPP,” they concluded.
The authors conceded that the generalizability of their study was limited as it included veterans receiving care in the VHA.
SOURCE: Am J Prev Med. 2018 Sep 24. doi: 10.1016/j.amepre.2018.06.028
FROM AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Key clinical point: Online diabetes prevention programs (DPP) are as effective as in-person programs in terms of weight loss, and they have a wider reach.
Major finding: Participants enrolled in an intensive, multifaceted online DPP intervention had significant weight change of −4.7 kg at 6 months and −4.0 kg at 12-month follow-up, similar to that of participants enrolled in a face-to face program.
Study details: A large nonrandomized trial and a comparative analysis of individuals from a concurrent trial of two parallel in-person programs.
Disclosures: The Department of Veteran Affairs funded the study. One author reported co-owning shares in Amgen, and another reported receiving personal fees from two pharmaceutical companies.
Source: Am J Prev Med. 2018 Sep 24. doi: 10.1016/j.amepre.2018.06.028.
Nonablative laser adds benefits to low-dose isotretinoin as treatment for moderate to severe acne
A combination of low-dose isotretinoin and nonablative fractional laser (NAFL) was a safe and effective treatment for moderate to severe acne and also improved acne scars in a small Chinese study, investigators reported.
In the randomized, split-face, controlled study of 18 adult Asian patients with moderate to severe acne, low-dose isotretinoin alone effectively controlled papule and pustule acne lesions, whereas NAFL had the additional effect of reducing the number of comedones and improving boxcar atrophic scars, reported Weihui Zeng, MD, and associates from the department of dermatology at the Second Affiliated Hospital of Xi’an Jiaotong University, Shanxi, China.
The authors noted that many patients seen at their clinic cannot tolerate a 20 mg/day dose of isotretinoin because of severe mucocutaneous side effects and that treatment with nonablative lasers, which – in contrast to ablative lasers – use infrared radiation to penetrate the skin deeply and thereby selectively heat dermal tissue while sparing the epidermis, could be a treatment option for these patients.
Therefore, they set out to investigate a treatment plan combining 1,550-nm NAFL with low-dose isotretinoin (10 mg/day) in the 18 patients (mean age, 24 years; skin types II-IV) attending their outpatient dermatology clinic. Three laser treatments were administered at monthly intervals to one side of the face, with the other side of the face serving as a control. Each patient was on low-dose isotretinoin for 30-45 days before laser treatment. A revised Leeds acne-grading system was used.
At follow-up after the third treatment – 3 months after the first laser treatment – both sides of the face showed significant recovery in all participants, but there was greater improvement on the laser-treated side. The mean Leeds acne-grading scores decreased from 10.6 at baseline to 5.8 on the control side of the face, and from 10.4 at baseline to 3.5 on the laser-treated side. The changes in scores differed significantly between sides (P less than .05), and the number of comedones decreased more on the laser-treated side of the face than it did the control side.
Significant improvements were also seen with superficial scars (P less than .05) and deep boxcar atrophic scars (P less than .01) on the laser-treated sides of patients’ faces, compared with the control sides, but significant improvements were not seen with the number of papules and nodules or with icepick or rolling scars.
Patients reported discomfort after NAFL treatment, including pain (100%), sensation of heat (100%), erythema (94.5%), and edema (88.9%), which resolved spontaneously within 24 hours.
Most of the patients (n = 12; 66.7%) were satisfied after the last treatment, two (11.1%) were “very satisfied,” and four (22.2%) were neutral; none were dissatisfied.
“Low-dose isotretinoin effectively controlled papule and pustule acne lesions, whereas use of 1,550-nm Er:glass NAFL may significantly reduce the number of comedones and improve boxcar atrophic scars,” the authors wrote.
They authors reported no significant interest with commercial supporters.
SOURCE: Xia J et al. Dermatol Surg. 2018 Sep;44(9):1201-8.
A combination of low-dose isotretinoin and nonablative fractional laser (NAFL) was a safe and effective treatment for moderate to severe acne and also improved acne scars in a small Chinese study, investigators reported.
In the randomized, split-face, controlled study of 18 adult Asian patients with moderate to severe acne, low-dose isotretinoin alone effectively controlled papule and pustule acne lesions, whereas NAFL had the additional effect of reducing the number of comedones and improving boxcar atrophic scars, reported Weihui Zeng, MD, and associates from the department of dermatology at the Second Affiliated Hospital of Xi’an Jiaotong University, Shanxi, China.
The authors noted that many patients seen at their clinic cannot tolerate a 20 mg/day dose of isotretinoin because of severe mucocutaneous side effects and that treatment with nonablative lasers, which – in contrast to ablative lasers – use infrared radiation to penetrate the skin deeply and thereby selectively heat dermal tissue while sparing the epidermis, could be a treatment option for these patients.
Therefore, they set out to investigate a treatment plan combining 1,550-nm NAFL with low-dose isotretinoin (10 mg/day) in the 18 patients (mean age, 24 years; skin types II-IV) attending their outpatient dermatology clinic. Three laser treatments were administered at monthly intervals to one side of the face, with the other side of the face serving as a control. Each patient was on low-dose isotretinoin for 30-45 days before laser treatment. A revised Leeds acne-grading system was used.
At follow-up after the third treatment – 3 months after the first laser treatment – both sides of the face showed significant recovery in all participants, but there was greater improvement on the laser-treated side. The mean Leeds acne-grading scores decreased from 10.6 at baseline to 5.8 on the control side of the face, and from 10.4 at baseline to 3.5 on the laser-treated side. The changes in scores differed significantly between sides (P less than .05), and the number of comedones decreased more on the laser-treated side of the face than it did the control side.
Significant improvements were also seen with superficial scars (P less than .05) and deep boxcar atrophic scars (P less than .01) on the laser-treated sides of patients’ faces, compared with the control sides, but significant improvements were not seen with the number of papules and nodules or with icepick or rolling scars.
Patients reported discomfort after NAFL treatment, including pain (100%), sensation of heat (100%), erythema (94.5%), and edema (88.9%), which resolved spontaneously within 24 hours.
Most of the patients (n = 12; 66.7%) were satisfied after the last treatment, two (11.1%) were “very satisfied,” and four (22.2%) were neutral; none were dissatisfied.
“Low-dose isotretinoin effectively controlled papule and pustule acne lesions, whereas use of 1,550-nm Er:glass NAFL may significantly reduce the number of comedones and improve boxcar atrophic scars,” the authors wrote.
They authors reported no significant interest with commercial supporters.
SOURCE: Xia J et al. Dermatol Surg. 2018 Sep;44(9):1201-8.
A combination of low-dose isotretinoin and nonablative fractional laser (NAFL) was a safe and effective treatment for moderate to severe acne and also improved acne scars in a small Chinese study, investigators reported.
In the randomized, split-face, controlled study of 18 adult Asian patients with moderate to severe acne, low-dose isotretinoin alone effectively controlled papule and pustule acne lesions, whereas NAFL had the additional effect of reducing the number of comedones and improving boxcar atrophic scars, reported Weihui Zeng, MD, and associates from the department of dermatology at the Second Affiliated Hospital of Xi’an Jiaotong University, Shanxi, China.
The authors noted that many patients seen at their clinic cannot tolerate a 20 mg/day dose of isotretinoin because of severe mucocutaneous side effects and that treatment with nonablative lasers, which – in contrast to ablative lasers – use infrared radiation to penetrate the skin deeply and thereby selectively heat dermal tissue while sparing the epidermis, could be a treatment option for these patients.
Therefore, they set out to investigate a treatment plan combining 1,550-nm NAFL with low-dose isotretinoin (10 mg/day) in the 18 patients (mean age, 24 years; skin types II-IV) attending their outpatient dermatology clinic. Three laser treatments were administered at monthly intervals to one side of the face, with the other side of the face serving as a control. Each patient was on low-dose isotretinoin for 30-45 days before laser treatment. A revised Leeds acne-grading system was used.
At follow-up after the third treatment – 3 months after the first laser treatment – both sides of the face showed significant recovery in all participants, but there was greater improvement on the laser-treated side. The mean Leeds acne-grading scores decreased from 10.6 at baseline to 5.8 on the control side of the face, and from 10.4 at baseline to 3.5 on the laser-treated side. The changes in scores differed significantly between sides (P less than .05), and the number of comedones decreased more on the laser-treated side of the face than it did the control side.
Significant improvements were also seen with superficial scars (P less than .05) and deep boxcar atrophic scars (P less than .01) on the laser-treated sides of patients’ faces, compared with the control sides, but significant improvements were not seen with the number of papules and nodules or with icepick or rolling scars.
Patients reported discomfort after NAFL treatment, including pain (100%), sensation of heat (100%), erythema (94.5%), and edema (88.9%), which resolved spontaneously within 24 hours.
Most of the patients (n = 12; 66.7%) were satisfied after the last treatment, two (11.1%) were “very satisfied,” and four (22.2%) were neutral; none were dissatisfied.
“Low-dose isotretinoin effectively controlled papule and pustule acne lesions, whereas use of 1,550-nm Er:glass NAFL may significantly reduce the number of comedones and improve boxcar atrophic scars,” the authors wrote.
They authors reported no significant interest with commercial supporters.
SOURCE: Xia J et al. Dermatol Surg. 2018 Sep;44(9):1201-8.
FROM DERMATOLOGIC SURGERY
Key clinical point: Adding nonablative fractional laser (NAFL) treatment to low-dose isotretinoin may reduce comedones and improve boxcar atrophic scarring in people with moderate to severe acne .
Major finding: Low-dose isotretinoin effectively controlled papule and pustule acne lesions, whereas nonablative laser also reduced the number of comedones and improved boxcar atrophic scars.
Study details: A prospective randomized, controlled, split-face study of 18 Asian adult patients with moderate to severe acne vulgaris, treated with low-dose isotretinoin, as well as NAFL to one side of the face.
Disclosures: The authors reported no significant interests with commercial supporters.
Source: Xia J et al. Dermatol Surg. 2018 Sep;44(9):1201-8.