Two dosing regimens of certolizumab pegol in patients with active rheumatoid arthritis

Abstract

Objective: To investigate clinical efficacy and safety of 2 certolizumab pegol (CZP) maintenance dosing regimens plus methotrexate (MTX) in active rheumatoid arthritis (RA) patients achieving the American College of Rheumatology 20% improvement criteria (ACR20) after the CZP 200 mg every 2 weeks open-label run-in period.

Methods: DOSEFLEX (dosing flexibility) was a double-blind, placebo-controlled randomized study with an open-label run-in phase. During the run-in phase, all patients received CZP 400 mg (weeks 0, 2, and 4) and 200 mg every 2 weeks to week 16. Week 16 ACR20 responders were randomized 1:1:1 at week 18 to CZP 200 mg every 2 weeks, 400 mg every 4 weeks, or placebo.

Results: A total of 209 (of 333) patients were randomized at week 18 (CZP: 200 mg, n = 70; 400 mg, n = 70; placebo, n = 69). Groups had similar baseline characteristics (week 0). Week 34 ACR20 response rates were comparable between the CZP 200 mg every 2 weeks and the 400 mg every 4 weeks groups (67.1% versus 65.2%), which was significantly higher than placebo (44.9%; P = 0.009 and P = 0.017). ACR50/70 and remission criteria were met more frequently in CZP groups than placebo at week 34, with similar responses between anti-tumor necrosis factor-experienced and naive patients. Improvements from baseline Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and Health Assessment Questionnaire disability index scores were maintained in CZP groups from week 16 to 34 while worsening on placebo. Adverse event (AE) rates in the double-blind phase were 62.9% versus 60.9% versus 62.3%; serious AE rates were 7.1% versus 2.9% versus 0.0% (CZP 200 mg, 400 mg, and placebo groups).

Conclusion: In active RA patients with an incomplete MTX response, CZP 200 mg every 2 weeks and 400 mg every 4 weeks were comparable and better than placebo for maintaining clinical response to week 4 following a 16-week, open-label run-in phase.

Trial registration: ClinicalTrials.gov NCT00580840.

© 2015 The Authors. Arthritis Care & Research is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Figures

Figure 1

DOSEFLEX (dosing flexibility) study design (A) and patient disposition in the DOSEFLEX study (B). ACR = American College of Rheumatology; Q2W = every 2 weeks; MTX = methotrexate; RA = rheumatoid arthritis; CZP = certolizumab pegol; Q4W = every 4 weeks; anti-TNF = anti–tumor necrosis factor; PBO = placebo.

Figure 2

Outcomes at the end of the run-in phase at week 16, where all patients were treated with certolizumab pegol (CZP) 200 mg every 2 weeks (Q2W). A, Kinetics of the American College of Rheumatology 20% improvement (ACR20)/ACR50/ACR70 responses (modified enrolled set, nonresponder imputation) and B, the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28[ESR]), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI) disease activity states (modified enrolled set, last observation carried forward). MTX = methotrexate; LDA = low disease activity; MDA = moderate disease activity; HAD = high disease activity.

Figure 3

Outcomes at week 34, the end of the double-blind phase. A, American College of Rheumatology 20% improvement (ACR20)/ACR50/ACR70 responses at week 34 (nonresponder imputation); B, Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28[ESR]), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI) disease activity states at week 34 (last observation carried forward [LOCF]); C, mean change from baseline in DAS28(ESR) to week 34 (LOCF); D, mean change from baseline in Health Assessment Questionnaire disability index (HAQ-DI) to week 34 (LOCF). CZP = certolizumab pegol; MTX = methotrexate; Q2W = every 2 weeks; Q4W = every 4 weeks; LDA = low disease activity; MDA = moderate disease activity; HDA = high disease activity.

Figure 4

Clinical outcomes at the end of the double-blind phase (week 34), stratified by prior anti–tumor necrosis factor (anti-TNF) exposure. A, American College of Rheumatology 20% improvement (ACR20)/ACR50/ACR70 responses at week 34 (nonresponder imputation); B, Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28[ESR]), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI) disease activity states at week 34 (last observation carried forward). CZP = certolizumab pegol; Q2W = every 2 weeks; MTX = methotrexate; Q4W = every 4 weeks.