Tocilizumab versus adalimumab for rheumatoid arthritis – Authors’ reply

Abstract

We appreciate the comments by David Felson on our report.1Gabay C Emery P van Vollenhoven R et al.Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial.Lancet. 2013; 381: 1541-1550Summary Full Text Full Text PDF PubMed Scopus (481) Google Scholar In addition to evaluating remission—defined as disease activity score using 28 joints (DAS28) of less than 2·6—we did exploratory post-hoc analyses to assess clinical disease activity index (CDAI), simplified disease activity index (SDAI), and American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean-based remission rates. Consistent with results using remission defined as DAS28 of less than 2·6, more patients who received tocilizumab achieved remission using these alternative criteria than patients who received adalimumab (CDAI: 17·2% vs 9·3%, p=0·0389; SDAI: 18·4% vs 8·0%, p<0·0067; and ACR/EULAR Boolean-based remission: 18·4% vs 11·1%, p=0·0569). As Felson noted, we stated that the efficacy results for adalimumab in the ADACTA trial were similar to those published previously, citing a study of adalimumab as monotherapy conducted by van de Putte and colleagues.2van de Putte LBA Atkins C Malaise M et al.Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed.Ann Rheum Dis. 2004; 63: 508-516Crossref PubMed Scopus (536) Google Scholar Aaltonen and colleagues’ meta-analysis3Aaltonen KJ Virkki LM Malmivaara A Konttinen YT Nordstrom DC Blom M Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis.PLoS One. 2012; 7: e30275Crossref PubMed Scopus (198) Google Scholar cited by Felson reports ACR50 responses for five adalimumab trials—three of which include adalimumab as combination therapy and two of which2van de Putte LBA Atkins C Malaise M et al.Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed.Ann Rheum Dis. 2004; 63: 508-516Crossref PubMed Scopus (536) Google Scholar, 4Miyasaka N Clinical investigation in highly disease-affected rheumatoid arthritis patients in Japan with adalimumab applying standard and general evaluation: the CHANGE study.Mod Rheumatol. 2008; 18: 252-262Crossref PubMed Scopus (0) Google Scholar focus on adalimumab monotherapy. ACR50 responses in both monotherapy trials are comparable to those observed in the ADACTA trial. The report by Aaltonen and colleagues3Aaltonen KJ Virkki LM Malmivaara A Konttinen YT Nordstrom DC Blom M Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis.PLoS One. 2012; 7: e30275Crossref PubMed Scopus (198) Google Scholar showed no difference in efficacy between high and usual doses of TNF inhibitors, including adalimumab. In the ADACTA trial, patients who did not have improvement of at least 20% in tender and swollen joint counts could receive an increase to weekly administration in the blinded subcutaneous medication dose by becoming part of an escape arm. Results of a sensitivity analysis, including results for these escape patients, were consistent with those of the primary analysis: adjusted mean change from baseline in DAS28 was significantly greater in the tocilizumab group than in the adalimumab group (–3·3 vs −1·8; difference −1·5; 95% CI −1·8 to −1·1; p<0·0001). We declare that we have no conflicts of interest other than those disclosed in the original paper. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trialTocilizumab monotherapy was superior to adalimumab monotherapy for reduction of signs and symptoms of rheumatoid arthritis in patients for whom methotrexate was deemed inappropriate. The adverse event profiles of tocilizumab and adalimumab were consistent with previous findings. Full-Text PDF Tocilizumab versus adalimumab for rheumatoid arthritisCem Gabay and colleagues (May 4, p 1541)1 should be congratulated for carrying out a large-scale comparative study of biological agents in rheumatoid arthritis. Given the panoply of effective agents now available, comparative data are crucial and more of such studies are needed. However, I have two concerns about this study.1 Full-Text PDF