ACR-HYBRID ANALYSIS CONFIRMS BENEFIT OF CERTOLIZUMAB PEGOL WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: DATA FROM THE RAPID 1 AND 2 TRIALS

Background: Certolizumab pegol (CZP), a PEGylated monomeric tumour necrosis factor (TNF) inhibitor, showed significant clinical efficacy in 2 Phase III trials when analysed using conventional ACR 20/50/70 responses. The ACR-hybrid outcome was recently proposed to provide metrological advantages over classic ACR 20/50/70 responses, since it equally weights mean changes in all ACR components, allowing for detection of smaller differences between active and placebo (PBO) therapies.Objectives: To evaluate the results from RAPID 1 and 2 (Phase III, randomised, controlled trials of 52 and 24 weeks' duration, respectively) using ACR-hybrid responses.Methods: In both RAPID 1 and 2, patients with active rheumatoid arthritis (RA) were randomised 2:2:1 to subcutaneously administered CZP (400 mg at Weeks 0, 2 and 4, followed by 200 or 400 mg every 2 weeks) or PBO, added to stable-dose MTX. Patients failing to achieve ACR20 responses at both Weeks 12 and 14 were withdrawn at Week 16 and could enter an open-label extension study. ACR-hybrid scores were determined by LOCF utilizing mean % changes from baseline bounded to +/- 100% in all 7 ACR core measures for each patient and banding each patient according to ACR 20/50/70 responses. If a patient withdrew or used rescue medication, ACR-hybrid scores were carried forward from that point onwards.Results: 982 (RAPID 1) and 619 (RAPID 2) patients were randomised. In both trials, patients receiving CZP + MTX had higher ACR-hybrid responses than PBO at all visits, with an onset of responses measured as early as Week 1. At maximum benefit (between Weeks 12 and 16), median ACR-hybrid scores for CZP peaked at approximately 50 and remained stable out to 52 weeks (see figure). Median PBO scores remained below 10 throughout the study.Conclusion: ACR-hybrid responses reinforce the strong, consistent clinical efficacy of CZP in RA, shown previously with traditional ACR 20/50/70 analyses, and demonstrate a treatment benefit as early as the first week. Importantly, these analyses show that the overall clinical response to PBO is negligible. This underlies the concern about extended PBO treatment in RA clinical trials, and supports use of early rescue as employed in these trials.Citation: Ann Rheum Dis, volume 67, supplement II, year 2008, page 333Session: RA – Anti-TNF therapy