Gradual tapering TNF inhibitors versus conventional synthetic DMARDs after achieving controlled disease in patients with rheumatoid arthritis: first-year results of the randomised controlled TARA study.

OBJECTIVES: The aim of this study is to evaluate the effectiveness of two tapering strategies after achieving controlled disease in patients with rheumatoid arthritis (RA), during 1 year of follow-up. METHODS: In this multicentre single-blinded (research nurses) randomised controlled trial, patients with RA were included who achieved controlled disease, defined as a Disease Activity Score (DAS) ≤ 2.4 and a Swollen Joint Count (SJC) ≤ 1, treated with both a conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and a TNF inhibitor. Eligible patients were randomised into gradual tapering csDMARDs or TNF inhibitors. Medication was tapered if the RA was still under control, by cutting the dosage into half, a quarter and thereafter it was stopped. Primary outcome was proportion of patients with a disease flare, defined as DAS > 2.4 and/or SJC > 1. Secondary outcomes were DAS, European Quality of Life-5 Dimensions (EQ5D) and functional ability (Health Assessment Questionnaire Disability Index [HAQ-DI]) after 1 year and over time. RESULTS: A total of 189 patients were randomly assigned to tapering csDMARDs (n = 94) or tapering anti-TNF (n = 95). The cumulative flare rates in the csDMARD and anti-TNF tapering group were, respectively, 33 % (95% CI,24% to 43 %) and 43 % (95% CI, 33% to 53 % (p = 0.17). Mean DAS, HAQ-DI and EQ-5D did not differ between tapering groups after 1 year and over time. CONCLUSION: Up to 9 months, flare rates of tapering csDMARDs or TNF inhibitors were similar. After 1 year, a non-significant difference was found of 10 % favouring csDMARD tapering. Tapering TNF inhibitors was, therefore, not superior to tapering csDMARDs. From a societal perspective, it would be sensible to taper the TNF inhibitor first, because of possible cost reductions and less long-term side effects. TRIAL REGISTRATION NUMBER: NTR2754.

Predictive factors of radiological progression after 2†years of remission-steered treatment in early arthritis patients: a post hoc analysis of the IMPROVED study.

OBJECTIVES: To identify predictive factors of radiological progression in early arthritis patients treated by remission-steered treatment. METHODS: In the IMPROVED study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (disease activity score (DAS) <1.6 after 4 months) tapered prednisone to zero. Patients not in early remission were randomised to arm 1: MTX plus hydroxychloroquine, sulfasalazine and prednisone, or to arm 2: MTX plus adalimumab. Predictors of radiological progression (≥0.5 Sharp/van der Heijde score; SHS) after 2 years were assessed using logistic regression analysis. RESULTS: Median (IQR) SHS progression in 488 patients was 0 (0-0) point, without differences between RA or UA patients or between treatment arms. In only 50/488 patients, the SHS progression was ≥0.5: 33 (66%) were in the early DAS remission group, 9 (18%) in arm 1, 5 (10%) in arm 2, 3 (6%) in the outside of protocol group. Age (OR (95% CI): 1.03 (1.00 to 1.06)) and the combined presence of anticarbamylated protein antibodies (anti-CarP) and anticitrullinated protein antibodies (ACPA) (2.54 (1.16 to 5.58)) were independent predictors for SHS progression. Symptom duration <12 weeks showed a trend. CONCLUSIONS: After 2 years of remission steered treatment in early arthritis patients, there was limited SHS progression in only a small group of patients. Numerically, patients who had achieved early DAS remission had more SHS progression than other patients. Positivity for both anti-CarP and ACPA and age were independently associated with SHS progression. TRIAL REGISTRATION NUMBERS: ISRCTN Register number 11916566 and EudraCT number 2006 06186-16.

A multibiomarker disease activity score for rheumatoid arthritis predicts radiographic joint damage in the BeSt study.

OBJECTIVE: To determine whether a multibiomarker disease activity (MBDA) score predicts radiographic damage progression in the subsequent year in patients with early rheumatoid arthritis. METHODS: There were 180 serum samples available in the BeSt study (trial numbers NTR262, NTR 265): 91 at baseline (84 with radiographs available) and 89 at 1-year followup (81 with radiographs available). Radiographs were assessed using the Sharp/van der Heijde Score (SvdH). Twelve serum biomarkers were measured to determine MBDA scores using a validated algorithm. Receiver-operating curves and Poisson regression analyses were performed, with Disease Activity Score (DAS) and MBDA score as independent variables, and radiographic progression as dependent variable. RESULTS: At baseline, MBDA scores discriminated more between patients who developed radiographic progression (increase in SvdH≥5 points) and patients who did not [area under the curve (AUC) 0.767, 95% CI 0.639-0.896] than did DAS (AUC 0.521, 95% CI 0.358-0.684). At 1 year, MBDA score had an AUC of 0.691 (95% CI 0.453-0.929) and DAS had an AUC of 0.649 (95% CI 0.417-0.880). Adjusted for anticitrullinated protein antibody status and DAS, higher MBDA scores were associated with an increased risk for SvdH progression [relative risk (RR) 1.039, 95% CI 1.018-1.059 for baseline MBDA score; 1.037, 95% CI 1.009-1.065 for Year 1 MBDA score]. Categorized high MBDA scores were also correlated with SvdH progression (RR for high MBDA score at baseline 3.7; low or moderate MBDA score as reference). At 1 year, high MBDA score gave a RR of 4.6 compared to low MBDA score. CONCLUSION: MBDA scores predict radiographic damage progression at baseline and during disease course.