The early clinical course of infliximab treatment in rheumatoid arthritis: results from the REMARK observational study

Objective We aimed to describe patterns of disease activity during infliximab plus methotrexate (MIX) treatment and explore C-reactive protein (CRP) as a potential marker of early response. Methods REMARK was a phase IV, open-label, observational study of infliximab-naive adults with rheumatoid arthritis (RA) who received infliximab 3 mg/kg plus MTX for 14 weeks. Treatment response was evaluated in 3 subgroups: patients with <1 year disease duration who were TNF-inhibitor (TNFi)-naive, patients with year disease duration who were TNFi-naive, and patients who had previous TNFi failure or intolerance. In post hoc analyses, CRP kinetic profiles were analysed by EULAR response (good, moderate, non-response) in REMARK and in an independent replication with data from the ASPIRE study. Results In the efficacy-evaluable population (n=662), median 28-joint disease activity score (DAS28) improved from baseline to Week 14 (5.2 vs. 3.6, p<0.0001). Regardless of disease history subgroup, most patients had good or moderate EULAR responses at Weeks 2 (64.9%), 6(74.1%), and 14 (73.6%). DAS28 and its components did not differ across patient subgroups. Disease flare occurred in 16.2% of patients. CRP levels declined markedly at Week 2, but patients who were EULAR non-responders at Week 14 showed a CRP rebound at Weeks 6 and 14. This CRP pattern was independently replicated in data from ASPIRE. Adverse events were consistent with the known risk profile of infliximab. Conclusion Infliximab plus MIX treatment in patients with RA rapidly diminished disease activity. A unique pattern of CRP rebound was found in non-responders early in treatment.