TY - JOUR
T1 - Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated japanese patients with early rheumatoid arthritis
T2 - 52-week results of the hopeful-1 trial
AU - Yamanaka, Hisashi
AU - Ishiguro, Naoki
AU - Takeuchi, Tsutomu
AU - Miyasaka, Nobuyuki
AU - Mukai, Masaya
AU - Matsubara, Tsukasa
AU - Uchida, Shoji
AU - Akama, Hideto
AU - Kupper, Hartmut
AU - Arora, Vipin
AU - Tanaka, Yoshiya
N1 - Funding Information:
Funding: This work was supported by AbbVie GK (Tokyo, Japan) and Eisai (Tokyo, Japan).
Funding Information:
Disclosure statement: N.M. has received research grants from AbbVie GK, Astellas Pharmaceutical, Banyu Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Janssen Pharmaceuticals, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical and Teijin. H.Y. has received research grants from AbbVie GK, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Pfizer Japan, Takeda Industrial Pharmaceutical and UCB Japan, and speakers honoraria/consulting fees from AbbVie GK, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Pfizer Japan, Takeda Pharmaceutical and UCB Japan. V.A. is a full-time employee of AbbVie and may hold AbbVie stock or stock options. H.A. is an employee of Eisai, Tokyo, Japan. Y.T. has received consulting fees, speaking fees and/or honoraria from Mitsubishi-Tanabe Pharma, AbbVie GK, Eisai, Chugai Pharmaceutical, Janssen Pharmaceutical K.K., Santen Pharmaceutical, Pfizer Japan, Astellas Pharma, Daiichi-Sankyo, GlaxoSmithKline K.K., Astra-Zeneca, Otsuka Pharmaceutical, Actelion Pharmaceuticals Japan, Eli Lilly Japan K.K., Nippon Kayaku, UCB Japan, Quintiles Transnational Japan, Ono Pharmaceutical and Novartis Pharma K.K. Y.T. has received research grants from Bristol-Myers Squibb, MSD K.K., Chugai Pharmaceutical, Mitsubishi-Tanabe Pharma, Astellas Pharma, AbbVie GK, Eisai and Janssen Pharmaceutical K.K. N.I. has received research grants from Astellas Pharmaceutical, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharmaceutical, Takeda Pharmaceutical, AbbVie and Janssen Pharmaceutical. M.M. has received research grants from AbbVie GK, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Pfizer Japan, Bristol-Myers Squibb and Otsuka Pharmaceutical. S.U. has received research grants from AbbVie GK. T.M. has received research grants from Chugai Pharmaceutical, Bristol-Myers Squibb, Nippon Kayaku, Otsuka Pharmaceutical, Takeda Pharmaceutical, Eli Lilly Japan K.K., Eli Lilly and Company, Astellas Pharma Pfizer Japan, AstraZeneca K.K. and Santen Pharmaceutical. T.T. has received grants from Abbott Japan, Astellas Pharma, Bristol-Myers K.K., Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Pfizer Japan, Sanofi-Aventis K.K., Santen Pharmaceutical, Takeda Pharmaceutical, Teijin Pharma, AbbVie GK, Asahikasei Pharma and Taisho Toyama Pharmaceutical; speaking fees from Abbott Japan, Bristol-Myers K.K., Chugai Pharmaceutical, Eisai, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical, Astellas Pharma and Diaichi Sankyo; and consultant fees from Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma, Asahi Kasei Medical K.K., AbbVie GK and Daiichi Sankyo. H.K. is a full-time employee of AbbVie and may hold AbbVie stock or stock options.
PY - 2014/5
Y1 - 2014/5
N2 - 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 ΔmTSS 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.
AB - 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 ΔmTSS 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.
KW - Adalimumab
KW - Japanese patients
KW - MTX naive
KW - Rheumatoid arthritis
KW - Safety
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U2 - 10.1093/rheumatology/ket465
DO - 10.1093/rheumatology/ket465
M3 - Article
C2 - 24441150
AN - SCOPUS:84898785888
VL - 53
SP - 904
EP - 913
JO - Rheumatology and Rehabilitation
JF - Rheumatology and Rehabilitation
SN - 1462-0324
IS - 5
M1 - ket465
ER -