POS0648 EFFICACY AND SAFETY OF LOW OR HIGH DOSE METHOTREXATE IN COMBINATION WITH ADALIMUMAB IN PATIENTS WITH ELDERLY-ONSET RHEUMATOID ARTHRITIS: RESULTS FROM THE RANDOMISED, CONTROLLED MIRACLE TRIAL (2024)

Abstract

Background: Elderly-onset rheumatoid arthritis (EORA) is reported to present with higher disease activity and greater disability at diagnosis, but comorbidities and adverse events are also more frequent, thus the treatment of these patients is challenging. The MIRACLE trial demonstrated the non-inferiority of efficacy of reduced dose of concomitant methotrexate compared to maximum tolerated dose of methotrexate in combination with adalimumab. Whether this result can be applied to the elderly population needs to be evaluated.

Objectives: To clarify the efficacy and safety of reduced dose of methotrexate in combination with adalimumab comparing to maximum tolerated dose of methotrexate in EORA.

Methods: The MIRACLE trial (NCT03505008) was a multinational, randomised trial in patients with RA with inadequate response to methotrexate. Three hundred methotrexate-naive patients were enrolled in the study and started methotrexate with an increase to maximum tolerated dose. Patients who did not achieve remission according to simplified disease activity index (SDAI) at week 24 were randomised to the continued dose or the reduced dose of methotrexate group and started subcutaneous adalimumab 40 mg every other week [1]. In the current analysis, we focused on 144 EORA patients aged 60 or older and evaluated the efficacy and safety of reduced dose of methotrexate with adalimumab.

Conclusion: In the MIRACLE trial, half of patients were diagnosed with the age of 60 or older. When treated with methotrexate monotherapy, the EORA patients had higher efficacy with higher total polyglutamates concentrations despite lower methotrexate doses. When combined with adalimumab, the SDAI remission rate was not different with a tendency of inferior HAQ remission rate in the reduced dose of methotrexate group. Safety profile tended to be superior to the reduced dose group.

Acknowledgements: We thank all the MIRACLE trial collaborators and staff at the participating centers for assistance with the care of the patients enrolled in this study and for their support in data collection.

Disclosure of Interests: Hiroya Tamai AbbVie, Eisai, Kei Ikeda Abbvie, Asahi-Kasei, Astellas, Bristol-Myers Suibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Mitsubishi-Tanabe, Gilead, UCB, Mitsubishi-Tanabe, Toshiaki Miyamoto AbbVie, Astellas, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kirin, Pfizer, UCB, Hiroaki Taguchi: None declared, Chang-Fu Kuo: None declared, Kichul Shin Novartis, Astellas, AbbVie, BMS, Yuhan, Shintaro Hirata AbbVie, AbbVie, Asahi-Kasei Pharma, Astellas, AstraZeneca, Ayumi, Bristol Myers Squibb, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Gilead Sciences, Glaxo SmithKline, Eli Lilly, Janssen, Novartis, Nippon Shinyaku, Pfizer, Taisho, Tanabe-Mitsubishi, UCB, Gilead Sciences, Janssen, Taisho, Asahi-Kasei Pharma, Eisai, Otsuka, Chugai, Eli Lilly, UCB, yutaka okano: None declared, Shinji Sato AbbVie, Asahi Kasei, Ayumi, Chugai, Diichi Sankyo, Eisai, Eli Lilly, Teijin, Pfizer, Hidekata Yasuoka AbbVie, Boehringer-Ingelheim, Gilead, Janssen, Nippon shinyaku, Asahi Kasei, Chugai, Eisai, Mitsubishi-Tanabe, Taisho, In Ah Choi AbbVie, Eisai, Sung-Hwan Park: None declared, Meng-Yu Weng Novartis, Eli Lilly, Chugai, AbbVie, AbbVie, Masataka Kuwana AbbVie, Asahi Kasei, Astellas, Boehringer Ingelheim, Chugai, Nippon Shinyaku, Mitsubishi-Tanabe, Boehringer Ingelheim, Kissei, Mochida, Boehringer Ingelheim, Ono, MBL, Yun Jong Lee Yuhan, Tomonori Ishii AbbVie, Asahi Kasei, Astellas, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Gilead, Glaxo Smith Kline, Janssen, Novartis, Pfizer, Jinhyun Kim: None declared, Hideto Kameda AbbVie, Asahi Kasei, Astellas, Boehringer, Bristol-Myers, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, UCB, AbbVie, Asahi Kasei, Boehringer, Chugai, Eisai, Mitsubishi-Tanabe, Taisho, Toshihisa Kojima AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Pfizer, Taisho, UCB, Han Joo Baek: None declared, Ping-Ning Hsu: None declared, Chun-Ming Huang AbbVie, Pfizer, Tien-Tsai Cheng AbbVie, AbbVie, Wan-Yu Sung: None declared, Wen-Chan Tsai: None declared, Takehiro Taninaga Eisai, Eisai, Masahiko Mori Eisai, Eisai, Hideaki Miyagishi Eisai, Eisai, Yasunori Sato Eisai, Kowa, Mochida, Tsutomu Takeuchi AbbVie, Asahi Kasei, Astellas, AstraZeneca, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Mitsubishi-Tanabe, Nippon Kayaku, Novartis, Pfizer, Sanofi, Taisho, UCB, AbbVie, Chugai, Eli Lilly, Gilead, Mitsubishi-Tanabe, AbbVie, Asahi Kasei, Ayumi, Boehringer-Ingelheim, Chugai, Eisai, Eli Lilly, Mitsubishi-Tanabe, Sanofi, Taisho, UCB, Yuko Kaneko AbbVie, Asahi Kasei, Astellas, AstraZeneca, Ayumi, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Glaxo Smith Kline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, Taisho, UCB, AbbVie, Asahi Kasei, Ayumi, Boehringer Ingelheim, Chugai, Eisai, Gilead, Mitsubishi-Tanabe, Taisho, UCB.