IntroductionUK 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.MethodsThe 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.ResultsACPA 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.ConclusionsACPA 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 registrationCurrent Controlled Trials ISRCTN32484878
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.
Gout is the most common inflammatory arthritis and causes significant pain and disability [...]
Background Takayasu arteritis (TA) is a chronic granulomatous large vessel vasculitis. Patients typically receive immunosuppressive therapies, often continued indefinitely. Despite recent publication of recommendations for treatment initiation in TA, there is limited data on whether immunosuppressive treatments can ever be safely withdrawn. Our aim was to investigate the characteristics and outcomes of patients in long-term remission in whom immunosuppressive treatment had been stopped. Methods Clinical and radiographic data from a cohort of 160 TA patients followed-up over 20 years in a single tertiary specialist centre were analysed cross-sectionally, identifying those in whom immunosuppressive treatment was fully withdrawn. Baseline demographic data was collected and compared to those remaining on treatment. Outcomes assessed included status of follow-up imaging, change in inflammatory markers (CRP and ESR) and National Institute of Health (NIH) scores where data was available. A Mann Whitney U test was used for statistical analysis. Results Of the 160 patients analysed, 134 required treatment of whom 22 (16%) (all female, median age 47 years) had treatment fully withdrawn, after receiving immunosuppression for >6 months. Median age at diagnosis was 30 years and median number of arteries involved was 3. In those remaining on treatment, 89% were female (median age 47 years). All those withdrawn from treatment had received prednisolone, 15 methotrexate, 8 azathioprine, 2 mycophenolate and 2 cyclophosphamides. Median duration of treatment was 106 months (IQR 104 months). Median time from treatment cessation to analysis was 26 months (IQR 67 months). All 22 patients remained alive at the time of analysis, 17 (77%) had follow-up imaging post-treatment withdrawal (5 currently awaited). Only one patient suffered a disease flare after immunosuppression was stopped. This occurred 4 months post-withdrawal, confirmed by imaging with a positive FDG-PET scan, concurrent increases in inflammatory markers and NIH score consistent with new active disease. In the 21 cases in whom treatment was successfully withdrawn, CRP and ESR results pre- and post-treatment cessation were not significantly different (p = 0.944 and p = 0.322 respectively). Likewise, NIH scores compared pre- and post-treatment withdrawal revealed a median change 0 (range -1 to + 3). Conclusion Little data exists on the cessation of immunosuppression in complex rheumatic disease. Of 160 TA patients, 21/22 patients off treatment had stable outcomes. The baseline characteristics of this sub-group did not differ significantly from the whole cohort, however none of them had ever received biological therapy, suggesting a less refractory course. Although these data demonstrate that immunosuppression can be safely withdrawn, the median duration of treatment was 106 months, raising the question of whether withdrawal should be attempted earlier. Biomarkers are required to help identify those in whom treatment can be withdrawn. We aim to develop protocols to facilitate safe treatment cessation in order to minimise treatment-related side-effects and with potential economic impact. Disclosures C. Dahanayake None. R. Maughan None. T. Youngstein None. J.C. Mason Other; Professor Mason has participated in medical board meetings with Roche/Chugai.
Background/Aims Immunosuppression in Takayasu arteritis (TA) reduces the risk of arterial disease progression. However, long-term use of glucocorticoids (GC) and other agents carries risk, particularly as patients age. GC tapering practice can vary and there are no guidelines on the safety of treatment cessation due to a lack of data. This study describes the cessation of treatment in a large single-centre cohort and evaluates the baseline, clinical and treatment parameters associated with successful treatment stop. Methods The Imperial College Takayasu Arteritis Cohort (UK) was reviewed retrospectively; 158 patients, median follow-up 8.4 [5-13.6] years. Patients with data available within 1 year of audit (31/03/2021) were analysed. Treatment was defined as > 6 months of GC, csDMARD or biologic medication and cessation as stopping treatment for >1 year. Cessation safety was assessed by serial angiography (whole aorta MRI or CT) and NIH disease activity scoring. Baseline demographic, clinical and treatment parameters as well as initial treatment responses were compared for cessation and non-cessation cases. Data are median [IQR], comparisons are non-parametric for continuous variables. Results Of 129 (82%) cases requiring treatment, 107 (83%) remained in care. 29 (27.1%) cases of cessation were identified, time off-treatment was 3.6 [2.5-8.2] years. For 25 (86%) cessation cases, treatment withdrawal was due to sustained quiescence. Infection, non-adherence and tolerance accelerated cessation in 4 cases. Long-term inactivity was confirmed by disease activity scoring in all cases and by angiography where available (23 cases). No instances of treatment restart were observed. Baseline demographic and disease severity parameters were similar in cessation and non-cessation patients (Table). Cessation cases had lower GC doses after 2 years of treatment and a trend towards lower disease activity, suggesting better responses. Relatedly, biologic administration (reserved for refractory disease) was markedly lower in the cessation group. Finally, cessation cases had earlier treatment start years, were older at audit and had an increased proportion of Numano Type V classification. Conclusion In TA, complete treatment cessation is feasible and safe in a proportion of cases. Initial treatment response, treatment duration and Numano type V arterial involvement are potential predictors of successful treatment cessation and may aid future stratification strategies after validation. Disclosure R.T. Maughan: None. A. Porter: None. C. Dahanayake: None. C. Ianonne: None. R. Alapat: None. C. Pericleous: None. T.A. Youngstein: None. J. Mason: None.
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