Variable impacts of different remission states on health-related quality of life in rheumatoid arthritis.

OBJECTIVES: Targeting remission in rheumatoid arthritis (RA) improves health-related quality of life (HRQoL) and disability. However, the impacts of different remission criteria and durations and their frequencies are uncertain. Our observational study assessed these factors. METHODS: We recruited RA patients with disease durations <10 years, stable suppressive therapies and stable disease activity scores for 28 joints using ESR (DAS28-ESR) ≤3.2. Intermittent and sustained remisisons were classified using DAS28ESR, simple disease activity index (SDAI) and ACR/EULAR Boolean criteria. HRQoL, measured using SF-36, fatigue, EuroQol and health assessment questionnaire (HAQ) was compared using time-integrated areas under the curve (AUC). RESULTS: 104 patients were enrolled and followed for 12 months. DAS28-ESR remissions were intermittent in 42%, sustained in 47% and absent in 11%. Boolean remissions were intermittent in 38%, sustained in 10% and absent in 52%. Baseline remissions by all criteria significantly improved HAQ, Euroqol, SF36 and fatigue scores compared with low disease activity (LDAS); AUCs showed significant benefits for all HRQoLs persisted over 12-months. Boolean remissions achieved most benefits. Over time all remission states gave significantly better HRQoL scores than LDAS. Sustained DAS28ESR and SDAI remissions improved HRQoL more than intermittent remissions. Sustained and intermittent Boolean remissions gave similar improvements. Analysis of SF-36 domains showed even sustained Boolean remissions failed to optimise pain and fatigue. CONCLUSIONS: All remissions improve HRQoL but different criteria have variable impacts. Boolean remission had most impact but occurred least. There are trade-off between optimising individual impacts (Boolean remissions) and achieving maximal overall impacts (DAS28-ESR remissions).

Attitudes and Behaviors of Patients With Rheumatic Diseases During the Early Stages of the COVID-19 Outbreak.

OBJECTIVE: To evaluate attitudes and behaviors of patients with rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: An online survey delivered by text message to 4695 patients on follow-up at a tertiary rheumatology center. Latent class analysis was performed on the survey variables. RESULTS: There were 2239 (47.7%) who responded to the survey and 3 clusters were identified. Cluster 3 (C3) was defined by patients who were most worried about COVID-19, more likely to wear face masks, and more likely to alter or stop their medications. Patients in C3 were more likely to be female, Malay, and unemployed. CONCLUSION: We identified 3 clusters with different healthcare beliefs and distinct sociodemographics.

A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis.

OBJECTIVE: We examined how combination DMARD therapies and TNF inhibitors therapies plus MTX (TNF/MTX) affect clinical and radiological outcomes compared with MTX monotherapy in early RA. METHODS: We systematically searched EMBASE, PubMed and Ovid Medline for randomized controlled trials (RCTs) of combination therapy in early RA. We evaluated ACR responses, withdrawals for inefficacy and toxicity, HAQ and radiographic progression. Meta-analysis using Review Manager evaluated random effects odds ratios (ORs) and random effects weighted mean differences (WMDs) between treatments. RESULTS: A preliminary search identified 2029 citations; 15 were relevant RCTs (4200 randomized patients). Patients with active disease were enrolled. Compared with MTX monotherapy, both combination DMARDs and TNF/MTX increased ACR20-70 responses (OR 1.64-2.02 and 2.03-2.30, respectively), reduced withdrawals for inefficacy (OR 0.52 and 0.29), reduced HAQ (WMD -0.17 and -0.16) and reduced annual X-ray progression (WMD -1.20 and -0.84%). DMARD combinations increased withdrawals for toxicity (OR 2.69; there was no difference with TNF/MTX). The only head-to-head RCT showed comparable efficacy for combination DMARDs and TNF/MTX combinations. CONCLUSIONS: In early active RA, both combination DMARDs and TNF/MTX are more effective than MTX monotherapy. DMARD and TNF/MTX combinations had equal efficacy on ACR response, withdrawals for inefficacy, disability and erosive progression. There is an apparent advantage for TNF/MTX combinations in the effect on toxicity with fewer consequent patients. We conclude that there is strong evidence in favour of combination treatment for RA but there is still uncertainty about which regimen is preferable.

Flares in Rheumatoid Arthritis Patients with Low Disease Activity: Predictability and Association with Worse Clinical Outcomes.

OBJECTIVE: To investigate predictors of flare in rheumatoid arthritis (RA) patients with low disease activity (LDA) and to evaluate the effect of flare on 12-month clinical outcomes. METHODS: Patients with RA who were taking disease-modifying antirheumatic drugs and had a stable 28-joint count Disease Activity Score (DAS28) < 3.2 were eligible for inclusion. At baseline and every 3 months, clinical (DAS28), functional [Health Assessment Questionnaire-Disability Index (HAQ-DI), EQ-5D, Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F), Medical Outcomes Study Short Form-36 (SF-36)], serum biomarkers [multibiomarker disease activity (MBDA) score, calprotectin, CXCL10], and imaging data were collected. Flare was defined as an increase in DAS28 compared with baseline of > 1.2, or > 0.6 if concurrent DAS28 ≥ 3.2. Cox regression analyses were used to identify baseline predictors of flare. Biomarkers were cross-sectionally correlated at time of flare. Linear regressions were performed to compare clinical outcomes after 1 year. RESULTS: Of 152 patients, 46 (30%) experienced a flare. Functional disability at baseline was associated with flare: HAQ-DI had an unadjusted HR 1.82 (95% CI 1.20-2.72) and EQ-5D had HR 0.20 (95% CI 0.07-0.57). In multivariate analyses, only HAQ-DI remained a significant independent predictor of flare (HR 1.76, 95% CI 1.05-2.93). At time of flare, DAS28 and its components significantly correlated with MBDA and calprotectin, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers. Patients who flared had significantly worse outcomes at 12 months (HAQ-DI, EQ-5D, FACIT-F, SF-36, and radiographic progression). CONCLUSION: Flares occur frequently in RA patients with LDA and are associated with worse disease activity, quality of life, and radiographic progression. Higher baseline HAQ-DI was modestly predictive of flare, while biomarker correlation at the time of flare suggests a noninflammatory component in a majority of events.

Clinical and serological predictors of remission in rheumatoid arthritis are dependent on treatment regimen.

OBJECTIVE: Early intensive treatment is now the cornerstone for the management of rheumatoid arthritis (RA). In the era of personalized medicine, when treatment is becoming more individualized, it is unclear from the current literature whether all patients with RA benefit equally from such intensive therapies. We investigated the benefit of different treatment regimens on remission rates when stratified to clinical and serological factors. METHODS: The Combination Anti-rheumatic Drugs in Early Rheumatoid Arthritis (CARDERA) trial recruited patients with RA of less than 2 years' duration who had active disease. The trial compared 4 treatment regimens: methotrexate monotherapy, 2 different double therapy regimens (methotrexate and cyclosporine or methotrexate and prednisolone) and 3-drug therapy. Clinical predictors included age, male sex, and tender joint count (TJC) and serological biomarkers included rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). RESULTS: Patients who were male, over 50 years, had ≥ 6 TJC, were RF-IgM-positive, or ACPA-positive were more likely to achieve remission at 24 months using 3-drug therapy compared to monotherapy (OR 2.99, 4.95, 2.71, 2.54, and 3.52, respectively). There were no differences in response to monotherapy and 3-drug therapy if patients were female, under 50 years, had < 6 TJC, or were seronegative. CONCLUSION: Early intensive regimens have become the gold standard in the treatment of early RA. Our study suggests that this intensive approach is only superior to monotherapy in certain subsets of patients. Although these are unlikely to be the only predictors of treatment response, our study brings us a step closer to achieving personalized medicine in RA.

ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial.

INTRODUCTION: UK guidelines recommend that all early active rheumatoid arthritis (RA) patients are offered combination disease-modifying antirheumatic drugs (DMARDs) and short-term corticosteroids. Anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA may differ in their treatment responses. We used data from a randomized controlled trial - the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial - to examine whether responses to intensive combination treatments in early RA differ by ACPA status. METHODS: The CARDERA trial randomized 467 early active RA patients to receive: (1) methotrexate, (2) methotrexate/ciclosporin, (3) methotrexate/prednisolone or (4) methotrexate/ciclosporin/prednisolone in a factorial-design. Patients were assessed every six months for two years. In this analysis we evaluated 431 patients with available ACPA status. To minimize multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline for each outcome (Larsen, disease activity scores on a 28-joint count (DAS28), Health Assessment Questionnaire (HAQ), EuroQol, SF-36 physical component summary (PCS) and mental component summary (MCS) scores). When a significant interaction was present, mean changes in outcomes were compared by treatment group at each time point using t-tests stratified by ACPA status. Odds ratios (ORs) for the onset of new erosions with treatment were calculated stratified by ACPA. RESULTS: ACPA status influenced the need for combination treatments to reduce radiological progression. ACPA-positive patients had significant reductions in Larsen score progression with all treatments. ACPA-positive patients receiving triple therapy had the greatest benefits: two-year mean Larsen score increases comprised 3.66 (95% confidence interval (CI) 2.27 to 5.05) with triple therapy and 9.58 (95% CI 6.76 to 12.39) with monotherapy; OR for new erosions with triple therapy versus monotherapy was 0.32 (95% CI 0.14 to 0.72; P = 0.003). ACPA-negative patients had minimal radiological progression irrespective of treatment. Corticosteroid's impact on improving DAS28/PCS scores was confined to ACPA-positive RA. CONCLUSIONS: ACPA status influences the need for combination DMARDs and high-dose tapering corticosteroids in early RA. In CARDERA, combination therapy was only required to prevent radiological progression in ACPA-positive patients; corticosteroids only provided significant disease activity and physical health improvements in ACPA-positive disease. This suggests ACPA is an important biomarker for guiding treatment decisions in early RA. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32484878.

Remission in early rheumatoid arthritis: predicting treatment response.

OBJECTIVE: Optimizing therapeutic strategies to induce remission requires an understanding of the initial features predicting remission. Currently no suitable model exists. We aim to develop a remission score using predictors of remission in early rheumatoid arthritis (RA). METHODS: We used a dataset from a UK randomized controlled trial that evaluated intensive treatment with conventional combination therapy, to develop a predictive model for 24-month remission. We studied 378 patients in the trial who received 24 months' treatment. Our model was validated using data from a UK observational cohort (Early RA Network, ERAN). A group of 194 patients was followed for 24 months. Remission was defined as 28-joint Disease Activity Score < 2.6. Logistic regression models were used to estimate the associations between remission and potential baseline predictors. RESULTS: Multivariate logistic regression analyses showed age, sex, and tender joint count (TJC) were independently associated with 24-month remission. The multivariate remission score developed using the trial data correctly classified 80% of patients. These findings were replicated using ERAN. The remission score has high specificity (98%) but low sensitivity (13%). Combining data from the trial and ERAN, we also developed a simplified remission score that showed that younger men with a TJC of 5 or lower were most likely to achieve 24-month remission. Remission was least likely in older women with high TJC. Rheumatoid factor, rheumatoid nodules, and radiographic damage did not predict remission. CONCLUSION: Remission can be predicted using a score based on age, sex, and TJC. The score is relevant in clinical trial and routine practice settings.

Remission in early rheumatoid arthritis.

OBJECTIVE: We systematically reviewed remission as an outcome measure in observational studies and randomized controlled trials (RCT) in early rheumatoid arthritis (RA). Our objectives were to identify its frequency using different criteria, to determine the influence of different treatment strategies on remission, and to review the effects of remission on radiological outcomes. METHODS: Pubmed, Medline and Embase were searched using the following terms: Early Rheumatoid Arthritis or Early RA combined with Remission, Treatment, anti-Tumor Necrosis Factor (TNF) or Disease-modifying Antirheumatic Drugs (DMARD). Remissions were reported using American College of Rheumatology (ACR) criteria and Disease Activity Score (DAS) criteria. RESULTS: Seventeen observational studies (4762 patients) reported remission in 27% of patients, 17% by ACR criteria and 33% by DAS criteria. Twenty RCT (4 comparing DMARD monotherapies, 13 comparing monotherapy with combination therapies, 3 comparing combination therapies) enrolled 4290 patients. ACR remissions occurred in 16% receiving DMARD monotherapy and 24% combination therapies (random effects OR 1.69, 95% CI 1.12-2.36). DAS remissions occurred in 26% and 42%, respectively (OR 2.01, 95% CI 1.46-2.78). Observational studies showed continuing radiological progression despite remission. RCT showed less radiological progression in remission when treated with combination therapy compared to monotherapies. CONCLUSION: Remission is a realistic treatment goal in early RA. Combination therapies using DMARD with or without TNF inhibitors increase remissions. Radiological progression occurred in remission but is reduced by combination therapies. ACR and DAS remission criteria are not directly comparable and standardization is needed.