Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial

Background Recently, we documented the likely non-inferiority of Combinatietherapie Bij Reumatoide Artritis (COBRA)-light therapy (methotrexate increased to 25mg/week with initial prednisolone 30mg/day) compared with the original COBRA therapy (methotrexate 7.5mg/week, sulfasalazine 2g/day, with initial prednisolone 60mg/day) after 26weeks in patients with early active rheumatoid arthritis (RA). Objective To assess the non-inferiority of COBRA-light versus COBRA after 1year in terms of disease activity (DAS44), functional outcome (Health Assessment Questionnaire (HAQ)) and radiographic progression (Sharp/van der Heijde score (SHS)), and to assess the effect of adding etanercept. Methods An open-label, randomised controlled, non-inferiority trial of 162 patients with active early RA, following a treat-to-target protocol incorporating the addition of etanercept if DAS44 1.6 at weeks 26 or 39. Results Both groups showed major improvements in DAS44 after 52weeks: mean (SD) -2.41 (1.2) in the COBRA and -2.02 (1.0) in the COBRA-light group (p=ns). In both groups, functional ability improved and radiological progression of joints was minimal. At least one adverse event was reported in 96% of the patients in both groups. In total, 25 serious adverse events occurred: 9 vs 16 in COBRA and COBRA-light, respectively. Treatment actually instituted was often less intensive than required by the protocol: of the total population, 108 patients (67%) required etanercept (more in the COBRA-light group), but only 67 of these (62%) actually received it. Conclusions Intensive COBRA or COBRA-light therapy has major, comparably favourable effects on disease activity, functional ability and radiological outcome after 1year in patients with early RA. Protocolised addition of etanercept was often not implemented by treating rheumatologists, and patients receiving it appeared to have limited added benefit, probably because of low disease activity levels at its initiation. Trial registration number: ISRCTN55552928.