Frequency and effectiveness of dose increase of adalimumab, etanercept, and infliximab in daily clinical practice.

Abstract

OBJECTIVE: To describe the frequency and effectiveness of dose increase of adalimumab, etanercept, and infliximab in the treatment of rheumatoid arthritis (RA) in daily clinical practice. METHODS: All RA patients with a dose increase of tumor necrosis factor (TNF)-blocking therapy between January 1997 and January 2008 were selected from a register including data from RA patients starting a first TNF-blocking agent (the Dutch Rheumatoid Arthritis Monitoring registry). The primary outcome was change in Disease Activity Score in 28 joints (DAS28) at 3 months after dose increase. Secondary outcomes were the change in DAS28 at 6 months after dose increase, the European League Against Rheumatism response rates, and the percentages of patients reaching a DAS28 of </=3.2 at 3 and at 6 months after dose increase. Furthermore, the effectiveness of dose increase was assessed for the different reasons for dose increase: nonresponse, loss of response, and partial response. RESULTS: During the study period, the dose was increased in 44 (12%) of the 368 adalimumab patients, 32 (8%) of the 420 etanercept patients, and 115 (36%) of the 323 infliximab patients. The change in DAS28 at 3 months and 6 months after dose increase was limited and only significant in etanercept patients at 3 months (-0.51; P = 0.035). Disease activity decreased significantly at 3 months from dose increase in the nonresponders and patients with loss of response (-0.66 and -0.99, respectively; both P = 0.001), but not in the partial responders. CONCLUSION: Although dose increase was applied in all 3 TNF-blocking agents in daily clinical practice, these results suggest that the effectiveness of dose increase is limited.