FRI0285 Initial Adalimumab plus Methotrexate Treatment Prevents Joint Destruction Irrespective of Treatment Duration in Japanese Patients with Early Rheumatoid Arthritis: Post-Hoc Analysis of HOPEFUL 1 and 2 Studies
Authors: Y. Tanaka, H. Yamanaka, N. Ishiguro, N. Miyasaka, K. Kawana, T. Kubo, A. Kuroki, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2014)

Background Information about the most effective use of adalimumab (ADA) to prevent joint destruction in Japanese patients with early rheumatoid arthritis (RA) is unavailable. Objectives To evaluate possible time to initiate ADA and the effect of treatment discontinuation on radiological outcomes. Methods Patients with early RA received blinded ADA 40 mg every other week (EOW) plus MTX 6-8 mg every week (EW) or MTX 6-8 mg EW alone for 26 weeks. Thereafter, all patients received open-label ADA 40 mg EOW plus MTX 6-8 mg EW for 26 weeks in the HOPEFUL 1 study. At week 52, patients could be enrolled in the 52-week observational, follow-up, HOPEFUL 2 study, during which time they received ADA plus MTX treatment (ADA-continued group), or MTX alone (ADA-withdrawal group) at the investigators' and patients' discretion. The objective of this post-hoc was to evaluate the change in modified total Sharp score (mTSS) from week 0 to week 104. Missing data were imputed using the linear extrapolation method. The 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR)Health Assessment Questionnaire Disability Index (HAQ-DI) at week 104, and factors associated with joint damage progression at week 104 were also examined. Results Among 334 patients enrolled, 276 completed the 52-week HOPEFUL 1 study and 220 were enrolled in the HOPEFUL 2 observational study. mTSS data were available for 182 patients who completed the HOPEFUL 2 study. Baseline characteristics including mTSS, DAS28-ESR, and HAQ-DI were comparable between the ADA plus MTX (n=109) and MTX (n=111) groups at week 0, and between the ADA-continued (n=106) and ADA-withdrawal (n=114) groups at week 52. At week 104, significantly more patients initially treated with ADA plus MTX had no radiographic progression (DmTSS ≤0.5), compared with those initially treated with MTX alone, irrespective of the duration of ADA treatment (table). Mean DAS28-ESR scores in patients initially treated with ADA plus MTX and MTX alone were 3.01 and 2.90, respectively, at week 104 ( P >0.5). Similarly, HAQ-DI scores at week 104 did not differ between the two groups. Factors associated with no radiographic progression at week 104 in all the patients were initial combined treatment with ADA plus MTX, and negative in MMP-3 at week 52 in multivariate analysis. ![Figure][1]</img> Conclusions Better inhibition of radiographic progression occurred in the initial combination therapy group. In this group, structural outcomes were similar whether ADA was continued or withdrawn at 52 weeks. Acknowledgements This study was sponsored by AbbVie and Eisai Co., Ltd. The design and study conduct support for this study was provided by AbbVie ([NCT01163292][2]). AbbVie participated in the interpretation of data, review, and approval of the publication. Disclosure of Interest Y. Tanaka Grant/research support: Bristol-Myers, Mitsubishi-Tanabe, AbbVie, MSD, Chugai, Astellas, Daiichi-Sankyo, Consultant for: Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei, Speakers bureau: Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei, H. Yamanaka Grant/research support: AbbVie GK; Bristol-Myers Squibb; Chugai Pharmaceutical Co; Eisai Co; Janssen Pharmaceutical K.K.; Mitsubishi Tanabe Pharma Corporation; Otsuka Pharmaceutical Co; Pfizer Japan Inc.; Takeda Industrial Pharmaceutical Co; and UCB Japan Co, Consultant for: AbbVie GK; Bristol-Myers Squibb; Chugai Pharmaceutical Co; Eisai Co; Janssen Pharmaceutical K.K.; Mitsubishi Tanabe Pharma Corporation; Otsuka Pharmaceutical Co; Pfizer Japan Inc.; Takeda Pharmaceutical Co; and UCB Japan Co., Speakers bureau: AbbVie GK; Bristol-Myers Squibb; Chugai Pharmaceutical Co; Eisai Co; Janssen Pharmaceutical K.K.; Mitsubishi Tanabe Pharma Corporation; Otsuka Pharmaceutical Co; Pfizer Japan Inc.; Takeda Pharmaceutical Co; and UCB Japan Co., N. Ishiguro Grant/research support: Abbott Japan; Astellas Pharmaceutical; Bristol-Myers Squibb; Chugai Pharmaceutical Co; Eisai Co; Janssen Pharma; Mitsubishi Tanabe Pharmaceutical Co; Pfizer Japan; and Takeda Pharma., N. Miyasaka Grant/research support: AbbVie GK; Astellas Pharmaceutical; Banyu Pharmaceutical; Chugai Pharmaceutical Co; Daiichi Sankyo Pharmaceutical Co; Eisai Co; Janssen Pharmaceuticals; Mitsubishi Tanabe Pharma Corporation; Takeda Pharmaceutical Co; and Teijin Limited., K. Kawana Employee of: Abbvie GK, T. Kubo Employee of: Abbvie GK, A. Kuroki Employee of: Abbvie GK, T. Takeuchi Grant/research support: AbbVie GK, Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nippon Shinyaku Co., Ltd., Pfizer Japan Inc., Sanofi–Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical., Speakers bureau: AbbVie GK, Ltd., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd. DOI 10.1136/annrheumdis-2014-eular.1414 [1]: pending:yes [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01163292&atom=%2Fannrheumdis%2F73%2FSuppl_2%2F487.1.atom