Background/Purpose: The objective of this systematic review was to evaluate the clinical evidence on the efficacy of different drug regimens for the treatment of early rheumatoid arthritis (RA). Different cut-off points have been used to define early RA. For this review we used duration of symptoms of ≤2 years, since this limit has been used in several trials.

Methods: We conducted an overview of systematic reviews. We searched for reviews indexed in The Cochrane Library and PubMed through June 2016. Our search strategy was restricted to reviews published in English with efficacy data. Two reviewers screened the list of included references in each review independently. Specific criteria included: results clearly specified for all patients (or subgroup reported) in study having ≤2 years of duration of RA, and at least six months of therapy and follow-up. Data extraction and assessment of the methodological quality of the trials using the Cochrane risk of bias tool was performed by one reviewer and crosschecked by another. Our primary outcome was the proportion of patients achieving an American College of Rheumatology (ACR) 50% response. Secondary outcomes included ACR improvement criteria of 20 and 70%, and safety. We performed direct comparison meta-analyses when data was available for 2 or more studies with the same interventions and outcomes.

Results: Out of 684 reviews, over 764 relevant citations evaluating steroids, DMARDs or biologics were reviewed. There were 6 type of comparisons, including: i) conventional DMARDs vs placebo; ii) conventional DMARDs monotherapy vs another conventional DMARD monotherapy (e.g., methotrexate (MTX) vs sulfasalazine (SSZ); iii) combination therapy with conventional DMARD vs monotherapy (e.g., MTX+SSZ, MTX+Cyclosporine, MTX+ bucillamine, MTX+ doxycycline); iv) combination therapy with conventional DMARDs and added prednisone vs monotherapy (with or without prednisone); v) combination therapy with conventional DMARDs and added prednisone vs combination therapy with conventional DMARDs; and vi) combination therapy with biologic DMARDs vs conventional DMARD monotherapy. ACR 50 response criteria rates were statistically significantly improved with most combination therapies (except MTX + cyclosporine, MTX + Bucillamine) compared with MTX alone at 1 and 2 years (RRs ranged between 1.4 (95%CI 1.1 to 1.6) and 10.3 (95% CI 1.5 to 69.6)). Similar effects were observed with ACR 20 response criteria rates (RRs ranged between 1.2 (95%CI 1.0 to 1.4) and 3.0 (95%CI 1.3 to 7.1)). No differences were observed among the various conventional DMARD monotherapies examined in these trials.

Conclusion: In patients with early onset disease of less than 2 years and active disease, MTX in combination with other conventional or biologic DMARD results in greater ACR responses compared with MTX or DMARD monotherapy. These findings suggest that patient may benefit by early combination therapy, either at onset, or possibly by adding a second conventional or biological DMARD early on.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatments-for-early-rheumatoid-arthritis-ra-a-systematic-review-of-randomized-controlled-trials/