American College of Rheumatology hybrid analysis of certolizumab pegol plus methotrexate in patients with active rheumatoid arthritis: data from a 52-week phase III trial

Abstract

Objective: The American College of Rheumatology (ACR) hybrid (a modified mean percent response to treatment) was officially recommended by the ACR as a revision to 20%, 50%, and 70% response criteria (ACR20/50/70) scores, but has not been tested in clinical trials. We performed a post hoc analysis of a phase III study of certolizumab pegol (Rheumatoid Arthritis Prevention of Structural Damage 1 [RAPID 1]) using the ACR hybrid.

Methods: Patients with active rheumatoid arthritis were randomized to certolizumab pegol (200 mg or 400 mg every other week) plus methotrexate or placebo plus methotrexate. ACR hybrid scores were compared with ACR20/50/70 outcomes.

Results: Differences between active treatment and placebo were significant throughout the study using the ACR20 and ACR hybrid outcomes. In the certolizumab pegol 200 mg group, the median ACR hybrid score at week 52 (last observation carried forward) was 49.99. A total of 258 (65.8%) of 392 and 172 (43.9%) of 392 patients had ACR20 and ACR50 responses, respectively. An additional 55 patients (14.0%) and 59 patients (15.1%) had mean improvements in ACR core measures of ≥ 20% and ≥ 50%, respectively, and therefore had positive ACR hybrid scores, despite lacking ACR20 and ACR50 responses, respectively. In the placebo group, median ACR hybrid scores were <10 at most time points; unlike other measures, the ACR hybrid measure indicated worsening scores for many patients.

Conclusion: ACR hybrid analysis had greater sensitivity than traditional ACR20/50/70 criteria, demonstrating improvements in ACR20 nonresponders treated with certolizumab pegol. Negligible benefit was observed with placebo using ACR hybrid analysis.

Copyright © 2011 by the American College of Rheumatology.

Figures

Figure 1

Efficacy of certolizumab pegol 200 mg plus MTX versus placebo plus MTX over time in the treatment of active RA in the intent-to-treat population of RAPID 1. Responses were significantly greater in patients treated with certolizumab pegol 200 mg plus MTX versus placebo plus MTX (P < 0.001 at Weeks 1–52). A. ACR20 response rates (logistic regression, nonresponder [NRI] imputation). Adapted from Keystone et al., Arthritis Rheum 2008;58(11):3319-29 (1). B. Median ACR hybrid scores (ANCOVA on the ranks, LOCF imputation). C. Mean changes from baseline in DAS28 (erythrocyte sedimentation rate) (ANCOVA, LOCF imputation).

Figure 2

Distribution of ACR hybrid scores (LOCF imputation) over time in patients treated with certolizumab pegol 200 mg plus MTX versus placebo plus MTX in the RAPID 1 trial. The number of subjects in the analysis varies slightly from the ITT population numbers due to nonimputable missing data for each visit. A. Week 1 (CZP 200 mg + MTX group: n = 385; PBO + MTX group: n = 194). B. Week 12 (CZP 200 mg + MTX group: n = 391; PBO + MTX group: n = 196). C. Week 52 (CZP 200 mg + MTX group: n = 392; PBO + MTX group: n = 196).