OBJECTIVES: We aimed to describe patterns of disease activity during infliximab plus methotrexate (MTX) 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-naïve 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)-naïve, patients with ≥ 1 year disease duration who were TNFi-naïve, 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. CONCLUSIONS: Infliximab plus MTX treatment in patients with RA rapidly diminished disease activity. A unique pattern of CRP rebound was found in non-responders early in treatment.
OBJECTIVES: We aimed to describe patterns of disease activity during infliximab plus methotrexate (MTX) 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-naïve 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)-naïve, patients with ≥ 1 year disease duration who were TNFi-naïve, 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. CONCLUSIONS:Infliximab plus MTX treatment in patients with RA rapidly diminished disease activity. A unique pattern of CRP rebound was found in non-responders early in treatment.
Authors: Mark C Genovese; Roy Fleischmann; Alan Kivitz; Eun-Bong Lee; Hubert van Hoogstraten; Toshio Kimura; Gregory St John; Erin K Mangan; Gerd R Burmester Journal: Arthritis Res Ther Date: 2020-06-10 Impact factor: 5.156