ObjectivesTo compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial.Methods400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered.ResultsData from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006).ConclusionsFor high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile.EudraCT number:2008-007225-39.

EudraCT-number 2008-007225-39 and NCT01172639; Results.

Vedolizumab therapy does not seem to show any efficacy in and might even induce arthritis and/or sacroiliitis. However, larger cohort studies are needed to provide information on the prevalence, the evolution and underlying mechanism.

IntroductionConsidering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial.MethodsDisease-modifying antirheumatic drug–naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti–citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3.2). Patients were randomized to 15 mg of MTX weekly (MTX with tight step-up (MTX-TSU)) or 15 mg of MTX weekly with prednisone bridging, starting at 30 mg and tapered to 5 mg daily from week 6 (COmbinatie therapie bij Reumatoïde Artritis (COBRA Slim)). A TSU approach was applied. Outcomes assessed were DAS28(CRP)-determined remission, cumulative disease activity, Health Assessment Questionnaire (HAQ) scores and adverse events (AEs) after 16 treatment weeks.ResultsWe analyzed 43 COBRA Slim and 47 MTX-TSU patients and found that 65.1% in the COBRA Slim group and 46.8% in the MTX-TSU group reached remission (P = 0.081). Mean ± standard deviation area under the curve values of DAS28(CRP) were 13.84 ± 4.58 and 11.18 ± 4.25 for the MTX-TSU and COBRA Slim patients, respectively (P = 0.006). More COBRA Slim patients had an HAQ score of 0 (51.2% versus 23.4%, P = 0.006) at week 16. Therapy-related AEs between groups did not differ.ConclusionIn patients with low-risk eRA, MTX with step-down glucocorticoid bridging seems more efficacious than MTX step-up monotherapy, with a comparable number of AEs observed over the first 16 treatment weeks.Trial registrationEU Clinical Trials Register Identifier: EudraCT number 2008-007225-39. Registered 5 November 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0611-8) contains supplementary material, which is available to authorized users.

Background In line with the window of opportunity theory, intensive DMARD combination therapy with glucocorticoids (GCs) is probably the most effective treatment approach for early Rheumatoid Arthritis (eRA), but the ideal content of the combination and the dose of GCs is not yet known. Objectives To compare the efficacy and safety of intensive treatment strategies associated with GCs at week (W)16, focusing on high risk patients. Methods CareRA is a prospective two-year investigator-initiated multicenter RCT rooted in daily practice. In this trial, 400 DMARD naïve eRA patients were stratified into high or low risk according to classical prognostic markers such as the presence of erosions, RF/ACPA and disease activity. High risk patients were randomized to 1/3 treatment strategies: COBRA Classic (MTX+ Sulphasalazine + 60mg GCs tapered to 7.5mg daily from W7), COBRA Slim (MTX + 30mg GCs tapered to 5 mg from W6) and COBRA Avant-Garde (MTX + Leflunomide + 30mg GCs tapered to 5 mg from W6). Treatment modifications to target low disease activity were mandatory from W8 onwards, if desirable and feasible according to the rheumatologist. The primary outcome was remission (DAS28(CRP) <2.6) at W16 (ITT analysis). Secondary endpoints were good EULAR response, clinically meaningful HAQ response and HAQ=0. Area under the curve (AUC) for DAS28(CRP) and proportion of treatment adaptations and GC injections were calculated. Adverse events (AEs) were registered. Missing data were imputed by the maximum likelihood method. Results 290 patients were stratified as high risk: 98 Classic, 98 Slim and 94 Avant-Garde patients. Remission was achieved in 70.4% COBRA CLASSIC patients, 73.5% COBRA SLIM patients, 68.1% COBRA AVANT-GARDE patients (p=0.713) at W16. No significant differences between groups were shown in the proportion with a good EULAR response, clinically meaningful HAQ response and HAQ=0 (all p>0.05). The AUC for DAS28(CRP) in the 3 treatment arms was equal (p=0.521). No difference in treatment adaptions or GCs injections was found at W16.Until W16, therapy related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). Conclusions At W16, MTX associated with a moderate step-down dose of GCs was as effective as DMARD combination therapies with moderate or even high step down GC doses in high-risk eRA. The short-term safety profile of MTX with GCs alone was more favorable. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2137