Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial

Rheumatology, May 2014

Yamanaka, Hisashi, Ishiguro, Naoki, Takeuchi, Tsutomu, Miyasaka, Nobuyuki, Mukai, Masaya, Matsubara, Tsukasa, Uchida, Shoji, Akama, Hideto, Kupper, Hartmut, Arora, Vipin, et al.

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Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial

please contact by guest on 04 May 2018 Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial Hisashi Yamanaka 2 Naoki Ishiguro 1 Tsutomu Takeuchi 0 Nobuyuki Miyasaka 6 Masaya Mukai 5 Tsukasa Matsubara 4 Shoji Uchida 3 Hideto Akama Hartmut Kupper Vipin Arora Yoshiya Tanaka 0 Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University , Shinjuku-ku 1 Department of Orthopedic Surgery, Nagoya University Graduate School and School of Medicine , Showa-ku, Nagoya 2 Institute of Rheumatology, Tokyo Women's Medical University , Shinjuku-ku, Tokyo 3 Uchida Clinic of Rheumatic Diseases , Sumida-ku, Tokyo 4 Matsubara Mayflower Hospital , Katou-shi, Hyogo 5 Division of Rheumatology and Hematology, Department of Medicine, Sapporo City General Hospital , Chuo-ku, Sapporo 6 Department of Medicine and Rheumatology, Graduate School of Tokyo Medical and Dental University , Bunkyo-ku, Tokyo Objective. The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity. Methods. Patients completing the 26-week, randomized, placebo-controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open-label adalimumab + MTX. Patients were assessed for mean change from baseline in the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and for the proportions of patients achieving clinical, functional or radiographic remission. Results. Of 333 patients assessed, 278 (137 from the initial adalimumab + MTX and 141 from the initial placebo + MTX groups) completed the 52-week study. Significant differences in clinical and functional parameters observed during the 26-week blinded period were not apparent following the addition of open-label adalimumab to MTX. Open-label adalimumab + MTX slowed radiographic progression through week 52 in both groups, but patients who received adalimumab + MTX throughout the study exhibited less radiographic progression than those who received placebo + MTX during the first 26 weeks (mean mTSS at week 52 = 2.56 vs 3.30, P < 0.001). Conclusion. Delayed addition of adalimumab in Japanese MTX-naive early RA patients did not impact clinical and functional outcomes at week 52 compared with the earlier addition of adalimumab. However, the accrual of significant structural damage during blinded placebo + MTX therapy contributed to the persistence of differences between the treatment strategies, suggesting that Japanese patients at risk for aggressive disease should benefit from the early inclusion of adalimumab + MTX combination therapy. Trial registration. ClinicalTrials.gov (http://clinicaltrials.gov/), NCT00870467. adalimumab; rheumatoid arthritis; Japanese patients; MTX naive; safety Introduction RA is a debilitating disease associated with inflammation of the synovial tissue in affected joints. Progression of the disease, if not abated, may lead to the erosive loss of bone and cartilage in affected joints and subsequent physical disability. The early inclusion of effective therapies aimed at tight control of disease activity minimizes the risk of irreversible erosive damage [ 1 4 ]. International recommendations suggest treatment initiation with MTX administered as monotherapy, which, in the event of an inadequate response, can then be supplemented with or switched to additional synthetic DMARDs or a biologic agent [ 5, 6 ]. Patients at risk for aggressive disease (e.g. those with autoantibody positivity, early erosive damage, etc.) may benefit from the early inclusion of a biologic agent, such as a TNF inhibitor, as a biologic combination with MTX suppresses inflammation and halts erosive damage more effectively than the addition of synthetic DMARDs [ 1, 7 ]. In fact, high disease activity along with the presence of risk factors may warrant the immediate inclusion of a TNF antagonist in the treatment regimen [ 5 ], given the relatively narrow window during which aggressive disease may be halted. Western trials of biologic agents have compared initial combination therapy vs initial MTX monotherapy in such patient populations [8 11], however, studies in Eastern populations are lacking, where environmental, genetic and medical and/or disease management differences may impact drug effectiveness and tolerability. The combination of adalimumab, a fully human monoclonal antibody against TNF-a, with MTX has been shown in global clinical trials to significantly reduce disease activity, improve physical function and prevent structural damage more effectively than MTX monotherapy in MTX-naive patients with early RA and high disease activity [ 8, 12 ]. The HOPEFUL-1 trial (adalimumab, a human antiTNF monoclonal antibody, outcome s (...truncated)


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Yamanaka, Hisashi, Ishiguro, Naoki, Takeuchi, Tsutomu, Miyasaka, Nobuyuki, Mukai, Masaya, Matsubara, Tsukasa, Uchida, Shoji, Akama, Hideto, Kupper, Hartmut, Arora, Vipin, Tanaka, Yoshiya. Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial, Rheumatology, 2014, pp. 904-913, Volume 53, Issue 5, DOI: 10.1093/rheumatology/ket465