Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial

Abstract

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.

A general practice perspective on early rheumatoid arthritis management: A qualitative study from Flanders

“…Initial intensive treatment strategies combining classical disease modifying anti-rheumatic drugs with rapid remission inducing agents like glucocorticoids or biologicals are the most effective and safe option for patients with early RA in achieving the 'window of opportunity' to control the disease (10)(11)(12)(13).…”

The impact on disability of initial treatment with methotrexate in patients with rheumatoid arthritis: results from the MARI study

“…In a Cochrane meta-analysis, which compared MTX monotherapy versus MTX combination therapy with nonbiologic DMARDs for RA, a significant improvement in physical function measured by HAQ was found in the MTX combination group, but only in MTX-inadequate responders (16). Conversely, more recent data from the CareRA trial did not show a different effect of MTX in combination with other DMARDs compared to MTX alone on HAQ scores in patients with early RA (17). This observation was not replicated, however, for patients treated with biological agents in the first 6 months, who were not more likely to have higher HAQ scores.…”

Rheumatoid Arthritis: A Novel Approach in Diagnosis and Treatment

“…In patients with RA, who were treated with glucocorticoides in low doses in combination with MTX better structural protection of affected joints was provided than in the group with monotherapy with MTX (85). After six months of therapy, the dose of glucocorticoides should be gradually decreased and stopped when DMARD-s achieved full effects (85,86). The clinical outcomes in patients with RA, in studies which compare MTX, sulfasalazine and leflunomide were similar, but MTX remains the core of therapy of RA especially because it optimizes effects of further therapy with biological drugs.…”

“…In the numerous clinical studies triple therapy for RA (MTX, sulfasalazine and hydroxychloroquine) was compared to monotherapy with MTX, but greater efficacy of triple therapy remains "blured", since in that arm of study glucocorticoides were applied ih higher doses. Further results of clinical randomised studies where lower dose of glucocorticoides was administered in tripleand in mono-therapy group have shown that no significant advantage was detected in the group with triple therapy, but only higher costs and more adverse effects (86,87). According to ACR guidelines, combination of cDMARD-s is not recommended as early first line therapy in patients with RA due to limitations of numerous clinical studies which investigate use of these kind of therapeutic strategy in RA.…”