Michelle Frits

Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR/EULAR remission criteria in an observational cohort

Objectives One goal of remission in rheumatoid arthritis (RA) is to halt joint damage. The authors assessed the progression of radiographic joint damage among RA patients in remission by the new ACR/EULAR criteria (Boolean approach) compared with remission thresholds for the simplified disease activity index (SDAI), clinical disease activity index (CDAI) and disease activity score based on 28 joints and C-reactive protein (DAS28-CRP) in an observational cohort, and evaluated the relationship between time in remission and radiographic joint damage. Methods 535 RA patients underwent physical examination and laboratory assessment at baseline, 1 and 2 years. Radiographs at baseline and 2 years were scored by the van der Heijde modified Sharp score (TSS). Positive likelihood ratios for a good radiographic outcome (change in TSS <1 unit/year) were calculated for each of the remission criteria. Radiographic progression was compared between patients in remission at none, one, two and three visits by χ2 goodness of fit statistics. Results 20% of patients in ACR/EULAR remission at baseline had radiographic progression, 24% in SDAI remission, 19% in CDAI remission and 30% of patients in DAS28–CRP remission. The positive likelihood ratio for good radiographic outcome was 2.6 for ACR/EULAR criteria, 2.1 for SDAI, 2.8 for CDAI and.1.5 for DAS28–CRP. Reduced radiographic progression was observed for patients with an increasing number of visits in remission (p<0.003 for all criteria, χ2 goodness of fit statistics). Conclusions Patients with RA in remission by any established criteria can experience radiographic progression. An increased number of visits in remission was associated with reduced radiographic damage.

Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study

IntroductionDisease remission has become a feasible goal for most rheumatoid arthritis (RA) patients; however, patient-reported symptoms, such as pain, may persist despite remission. We assessed the prevalence of pain in RA patients in remission according to the Disease Activity Score (DAS28-CRP4) and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria.MethodsData were analyzed from RA patients in the Brigham Rheumatoid Arthritis Sequential Study with data at baseline and 1 year. DAS28 remission was defined as DAS28-CRP4 <2.6. The ACR/EULAR remission criteria included (a) one or more swollen joints, (b) one or more tender joints, (c) C-reactive protein ≤1 mg/dl, and (d) patient global assessment score ≤1. Pain severity was measured by using the pain score from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ). The associations between baseline clinical predictors and MDHAQ pain at baseline and 1 year were assessed by using multivariable linear regression.ResultsAmong the 865 patients with data at baseline and 1 year, 157 (18.2%) met DAS28-CRP4 remission criteria at both time points. Thirty-seven (4.3%) met the ACR/EULAR remission criteria at baseline and 1 year. The prevalence of clinically significant pain (MDHAQ pain ≥4) at baseline ranged from 11.9% among patients meeting DAS28-CRP4 remission criteria to none among patients meeting ACR/EULAR remission criteria. Patient global assessment, MDHAQ function, MDHAQ fatigue, MDHAQ sleep, and arthritis self-efficacy were significantly associated with MDHAQ pain in cross-sectional (P ≤ 0.0005) and longitudinal analyses (P ≤ 0.03). Low swollen-joint counts were associated with high MDHAQ pain in longitudinal analyses (P = 0.02) but not cross-sectional analyses. Other measures of inflammatory disease activity and joint damage were not significantly associated with MDHAQ pain at baseline or at 1 year.ConclusionsClinically significant pain continues among a substantial proportion of patients in DAS28 remission but not among those in ACR/EULAR remission. Among patients in DAS28 remission, patient global assessment, disability, fatigue, sleep problems, and self-efficacy are strongly associated with pain severity at baseline and 1 year, whereas inflammatory disease activity and joint damage are not significantly associated with elevated pain severity at either baseline or 1 year.

Sustained rheumatoid arthritis remission is uncommon in clinical practice

IntroductionRemission is an important goal of therapy in rheumatoid arthritis (RA), but data on duration of remission are lacking. Our objective was to describe the duration of remission in RA, assessed by different criteria.MethodsWe evaluated patients from the Brigham and Womens Rheumatoid Arthritis Sequential Study (BRASS) not in remission at baseline with at least 2 years of follow-up. Remission was assessed according to the Disease Activity Score 28-C-reactive protein (DAS28-CRP4), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) scores, and the recently proposed American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria for remission. Analyses were performed by using Kaplan-Meier survival curves.ResultsWe identified 871 subjects with ≥2 years of follow-up. Of these subjects, 394 were in remission at one or more time-points and not in remission at baseline, according to at least one of the following criteria: DAS28-CRP < 2.6 (n = 309), DAS28-CRP < 2.3 (n = 275), SDAI (n = 168), CDAI (n = 170), and 2010 ACR/EULAR (n = 158). The median age for the 394 subjects at entrance to BRASS was 56 years; median disease duration was 8 years; 81% were female patients; and 72% were seropositive. Survival analysis performed separately for each remission criterion demonstrated that < 50% of subjects remained in remission 1 year later. Median remission survival time was 1 year. Kaplan-Meier curves of the various remission criteria did not significantly differ (P = 0.29 according to the log-rank test).ConclusionsThis study shows that in clinical practice, a minority of RA patients are in sustained remission.

The Association Between Reduction in Inflammation and Changes in Lipoprotein Levels and HDL Cholesterol Efflux Capacity in Rheumatoid Arthritis

Background Potent anti‐inflammatory rheumatoid arthritis (RA) treatments are associated with reduced cardiovascular risk as well as increases in low‐density lipoprotein (LDL) cholesterol. This apparent paradox may be explained by favorable changes in other lipid measurements. The objective of this study was to determine the longitudinal association between changes in inflammation with advanced lipoprotein measurements and high‐density lipoprotein (HDL) cholesterol efflux capacity. Methods and Results We conducted this study in a longitudinal RA cohort from a large academic center, including subjects with high‐sensitivity C‐reactive protein (hs‐CRP) reduction ≥10 mg/L at 2 time points 1 year apart. Subjects receiving statins during the study period or preceding 6 months were excluded. We compared total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B, and apolipoprotein A1 levels and HDL cholesterol efflux capacity at baseline and 1‐year follow‐up by using the paired t test. We also assessed the correlations between reductions in hs‐CRP with percentage change in lipid parameters. We studied 90 RA subjects (mean age 57 years, 89% female), all of whom were receiving disease‐modifying antirheumatic drugs. We observed a 7.2% increase in LDL cholesterol levels (P=0.02) and improvement in efflux capacity by 5.7% (P=0.002) between baseline and follow‐up, with a median hs‐CRP reduction of 23.5 mg/L. We observed significant correlations between reductions in hs‐CRP with increases in apolipoprotein A1 (r=0.27, P=0.01) and HDL cholesterol efflux capacity (r=0.24, P=0.02). Conclusion Among RA subjects experiencing reductions in hs‐CRP, we observed increased LDL cholesterol levels and concomitant improvements in HDL cholesterol efflux capacity. These findings provide further insight into lipid modulation and the beneficial effect of reduction in inflammation on lipids in vivo.

Subgrouping of Patients With Rheumatoid Arthritis Based on Pain, Fatigue, Inflammation, and Psychosocial Factors

Among patients with rheumatoid arthritis (RA), pain may be attributed to peripheral inflammation or other causes, such as central pain mechanisms. The aim of this study was to use self‐report measures and physical examination findings to identify clusters of RA patients who may have different causes of pain as well as different prognoses and treatment options.

Functional Impact of a Spectrum of Interstitial Lung Abnormalities in Rheumatoid Arthritis

BACKGROUND Approximately 10% of patients with rheumatoid arthritis (RA) have interstitial lung disease (ILD), and one-third have subclinical ILD on chest CT scan. In this study, we aimed to further characterize functional decrements in a spectrum of RA-associated ILD. METHODS All subjects were enrolled in the Brigham and Womens Hospital Rheumatoid Arthritis Sequential Study (BRASS). The presence of interstitial lung abnormalities (ILAs) on clinically indicated chest CT scans was determined using a previously validated sequential reading method. Univariate and multivariate analyses were used to assess the association between degree of ILAs and physiologic, functional, and demographic variables of interest. RESULTS Of 1,145 BRASS subjects, 91 subjects (8%) were included in this study. Twelve had radiologically severe ILAs, 34 had ILAs, and 38 had no ILAs on CT scan. Subjects with radiologically severe ILAs were older (P = .0037), had increased respiratory symptoms (cough, P = .027; dyspnea, P = .010), and more severe RA disease (rheumatoid factor, P = .018; total swollen joints, P = .046) compared with subjects with no ILAs. Participants also had a trend toward having an increased smoking history (P = .16) and having lower FVC % predicted (77% vs 94%, P = .097) and diffusion capacity of carbon monoxide % predicted (52% vs 77%, P = .068). Similar but attenuated increases in respiratory symptoms, functional decrements, and RA disease severity were observed in subjects with ILAs compared with those with no ILAs. CONCLUSIONS We have shown that patients with RA have varying degrees of ILAs that are associated with a spectrum of functional and physiologic decrements. Our findings suggest that improved risk stratification and detection of ILAs will provide a therapeutic window that could improve RA-ILD outcomes.

Detection of Rheumatoid Arthritis–Interstitial Lung Disease Is Enhanced by Serum Biomarkers

RATIONALE Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized. OBJECTIVES To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD. METHODS Subjects enrolled in Brigham and Womens Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. MEASUREMENTS AND MAIN RESULTS A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD. CONCLUSIONS Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.

Performance of matrix-based risk models for rapid radiographic progression in a cohort of patients with established rheumatoid arthritis.

Matrix‐based risk models have been proposed as a tool to predict rapid radiographic progression (RRP) in rheumatoid arthritis (RA), but the experience with such models is limited. We tested the performance of 3 risk models for RRP in an observational cohort.

Associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis.

Objective. To investigate the associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis (RA). Methods. We conducted a prospective study consisting of 662 patients with RA who were followed up to 7 years from the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study. Smoking and alcohol consumption were assessed through yearly questionnaires. The disease activity and functional status were measured annually by the Disease Activity Score examined in 28 commonly affected joints using C-reactive protein (DAS28-CRP3) and the Modified Health Assessment Questionnaire (MHAQ). Linear mixed models were developed to assess the longitudinal effects of smoking and alcohol consumption on DAS28-CRP3 and MHAQ after adjustment for potential confounders. The HLA-DRB1 shared epitope (HLA-SE) by smoking and alcohol interactions were also evaluated in the analysis. Results. The median followup time of the cohort was 4 years. Current smoking was not associated with DAS28-CRP3 in our study, but was associated with a higher MHAQ than nonsmokers with seropositive RA (p = 0.05). Alcohol consumption showed an approximate J-shaped relationship with MHAQ, with the minima occurring at 5.1–10.0 g/day. Compared to no alcohol use, alcohol consumption of 5.1–10.0 g/day was associated with a significant decrease of MHAQ (p = 0.02). When stratified by HLA-SE, the effect of alcohol consumption appeared to be stronger in HLA-SE–positive RA than HLA-SE–negative RA. Conclusion. We found that current smoking was associated with a worse functional status, while moderate alcohol consumption was associated with a better functional status in RA. Replications of these findings in other prospective studies are needed.

Flares in Rheumatoid Arthritis: Frequency and Management. A Report from the BRASS Registry

Objective. To describe the frequency, duration, and management of flares as reported by patients with rheumatoid arthritis (RA). Methods. Data were collected in a prospective observational study of patients with RA recruited from a single academic center and treated according to the rheumatologists’ discretion. Every 6 months, patients reported the number and duration of RA flares and described how these were managed in terms of adding or changing medication and use of nonpharmacologic strategies. Results. Of patients who reported flares at least once during the study, 74% reported having flares 6 months prior to study entry and 59% reported flares prior to the first 6-month visit. At subsequent visits, 54–57% reported having > 1 flare. Thirty percent of patients in remission reported flares. Flare duration lasted ≥ 2 weeks in 30%, 1–2 weeks in 13%, and < 1 week in 57%. Forty percent reported medication changes at the time of their flare; 16% changed medication and used nonpharmacologic strategies and 26% of patients reported no changes in treatment as a result of flares. Longer duration of flare was associated with changes in disease-modifying therapy. Conclusion. Patients with RA experienced flares more often when noted to be in higher disease activity states than when in remission and reported changes in disease-modifying antirheumatic drugs or biologics more frequently when flares were of longer duration. There is a need to prospectively study symptom intensity and duration of flare in relation to disease activity and consider self-management strategies in the development of a measure of flare.