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
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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
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)