Correspondence on ‘Five-year treat-to-target outcomes after methotrexate induction therapy with or without other csDMARDs and temporary glucocorticoids for rheumatoid arthritis in the CareRA trial’

Abstract

The 5year followup data of the CareRA cohort are interesting. However, a few points merit consideration and clarification. Findings in the highrisk group reaffirm the fact that upfront combination diseasemodifying antirheumatic drugs (DMARDs) are not needed even in patients of rheumatoid arthritis (RA) with poor prognostic factors, provided a treattotarget strategy is followed. However, we wish to draw attention to the lowrisk group which compared initial methotrexate (MTX) monotherapy to MTX+prednisolone bridging (COBRASlim). The results in the lowrisk group seem counterintuitive to previous landmark trials (including the BeSt and the TEAR) that found longterm outcomes to be essentially determined by treatingtotarget, with the intensity of initial treatment only guiding the rapidity of response achieved. 3 However, in the CareRAplus, the initial difference in disease activity between MTX monotherapy vs MTX+prednisolone bridging (COBRASlim) in the lowrisk group persisted for up to 5 years—this could reignite interest in the concept of ‘a timelimited window of opportunity’ in early RA. However, it must be stressed that any conclusions in the lowrisk group should be guarded, as the numbers included in this group (n=49 at the start of this longterm extension study; 38 by the end of followup at 5 years) were too few to draw any reliable conclusions. Unfortunately, there was no MTX monotherapy arm in the highrisk group which had more patients, and thus could have better answered the question whether addition of bridging glucocorticoids to initial MTX monotherapy improves longterm outcomes in early RA, when followed by a tight stepup approach to treatment target. Considering the little incremental response in any treatment arm after the first year, more details regarding the treatment escalation strategies followed after the protocolspecified two step escalation (step 1 and step 2) would be insightful. We would be interested in knowing the treatment changes (switches or additions) after the protocolised first year till year 5 (in the ~50% of patients who required such changes) and the final treatment patients were taking at the end of 5 years. Nevertheless, the authors must be congratulated for their study which has reaffirmed the fact that excellent results are possible with conventional synthetic DMARDs+prednisolone in a majority of cases and biological DMARDs are required in only a minority of patients (onefourth) with RA.