Research in context
Evidence before this study
The European League Against Rheumatism (EULAR) recommends early treatment in rheumatoid arthritis to achieve clinical remission (evidence level 1a). An individualised treat-to-target approach is recommended by the EULAR guideline, including biological disease-modifying antirheumatic drugs (DMARDs), if conventional synthetic DMARDs, with methotrexate as a first choice, do not achieve the treatment target (evidence level 1b). We did a PubMed search of publications dated up to March 21, 2016, for articles on the treatment of early rheumatoid arthritis with strategies including randomisation for double-blind addition of a registered biological DMARD or placebo from start of the trial to methotrexate as the only conventional synthetic DMARD. Using the search terms “rheumatoid arthritis”, “biologic” and “clinical trial”, we identified 17 original trials. In these studies, the arm with methotrexate and a biological showed greater efficacy compared with the methotrexate-monotherapy arms, except for two trials in which in the methotrexate comparator arm, methotrexate was combined with glucocorticoids. Although in several trials the biological was discontinued, generally the conventional synthetic DMARDs were continued. Only two trials reported on drug-free remission and only one trial had an individualised treat-to-target design.
Added value of this study
Our study applied a double-blind, double-dummy design with an individualised treat-to-target approach, similar to that used in clinical practice, in DMARD-naive patients with rheumatoid arthritis. The results from our study are therefore directly applicable to clinical practice. It compared the efficacy of adding a biological DMARD only when conventional synthetic DMARDs fail to induce remission, in line with international recommendations, versus initiating from the start of therapy a biological DMARD—ie, tocilizumab. The findings from our study showed that a greater proportion of patients achieved sustained remission on strategies using tocilizumab from treatment start (with or without methotrexate), than on the reference methotrexate-based strategy. The high proportions of patients in sustained remission and sustained drug-free remission after controlled withdrawal of both methotrexate and the biological are distinctive findings compared with previous studies. The results from our study indicate that drug-free remission is an achievable treatment goal. No additional safety issues were identified.
Implications of all the available evidence
Current management of early rheumatoid arthritis can be improved by initiating therapy with biological DMARDs from the start of therapy. Currently, an individualised tocilizumab-based strategy appears the most effective choice for a strategy aimed at drug-free remission. The challenge is to identify patients with early rheumatoid arthritis who will respond sufficiently to conventional synthetic DMARDs and do not need a biological DMARD. Drug-free remission will probably become a future treatment target.