Journal Article

POS0051 DRUG RETENTION AND REASONS FOR DISCONTINUATION OF BIOLOGICS AND JAK INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS – THE ANSWER COHORT STUDY

Hirao, M., Okita, Y., Ebina, K., Murata, K., Kumanogoh, A., Son, Y., Okano, T., Katayama, M., Nakata, K., Hashimoto, M., Yamamoto, W., Etani, Y., Amuro, H., Fujii, T., Hiramatsu, Y., Okada, S., Maeda, Y., Hara, R., Nagai, K., Ueda, Y.

2023

Overview

2022 EULAR recommendation announced that both biological disease-modifying antirheumatic drugs (bDMARDs) and janus kinase inhibitors (JAKi) are considered in the phase Ⅱ treatment of rheumatoid arthritis (RA). However, we still lack reliable evidence of direct comparison between these agents' retention, which may reflect effectiveness and safety. The aim of this multi-center (7 university-related hospitals)[1]-[3], retrospective study is to clarify the factors affecting treatment retention of bDMARDs and JAKi in a real-world setting. This study assessed 6,666 treatment courses of bDMARDs and JAKi introduced from 2001 to 2022 (TNF inhibitors [TNFi]=3,577, anti-IL-6 receptor antibody [aIL-6R]=1,497, cytotoxic T lymphocyte-associated antigen-4-Ig [CTLA4-Ig]=1,139, JAKi=453; Bio/JAK naive cases 55.4%, baseline age 58.8 years, female 82.6%, disease duration 9.7 years, DAS28-ESR 4.3, concomitant methotrexate [MTX] [52.8%], other csDMARDs [26.0%], and oral glucocorticoid [GC] [36.4%]). Reasons for discontinuation were classified into four categories by each attending physician: 1) lack of effectiveness (primary and secondary), 2) toxic adverse events (infection, malignancies, and cardiovascular events, et al.), 3) non-toxic reasons (patient preference, change in hospital, and pregnancy, et al.), and 4) remission. Retention rates of each discontinuation reason were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, concomitant GC, MTX, and other csDMARDs, switched number of bDMARDs or JAKi, and prior use of TNFi, aIL-6R, CTLA4-Ig, or JAKi) using Cox proportional hazards modeling. Adjusted retention rates for each discontinuation reason were as follows: due to lack of effectiveness was aIL-6R=80.9%, JAKi=75.2%, CTLA4-Ig=73.6%, and TNFi=66.1% (Cox P<0.001 between 4 groups) (figure 1a), due to toxic adverse events was CTLA4-Ig=88.0%, JAKi=86.4%, aIL-6R=84.1%, and TNFi=83.6% (Cox P=0.052) (figure 1b), due to non-toxic reasons was aIL-6R=86.9%, TNFi=85.9%, JAKi=85.9%, and CTLA4-Ig=82.6% (Cox P=0.064), and due to remission was JAKi=97.1%, CTLA4-Ig=96.7%, aIL-6R=96.0%, and TNFi=94.9% (Cox P=0.18). Compared to TNFi, aIL-6R (hazard ratio [HR]=0.54, 95%CI=0.47–0.61, P<0.001), JAKi (HR=0.69, 95%CI=0.56–0.85, P<0.001), and CTLA4-Ig (HR=0.75, 95%CI=0.66–0.86, P<0.001) showed lower discontinuation rate due to lack of effectiveness. Compared to TNFi, CTLA4-Ig showed lower discontinuation rate due to toxic adverse events (HR=0.77, 95%CI=0.63–0.93, P=0.008) and remission (HR=0.67, 95%CI=0.46–0.98, P=0.041). Other factors increasing drug discontinuation due to lack of effectiveness was switched number of bDMARDs or JAKi (HR=1.42, 95%CI=1.24–1.63, P<0.001), concomitant GC (HR=1.17, 95%CI=1.06–1.29, P=0.0018), and prior aIL-6R use (HR=1.24, 95%CI=1.05–1.45, P=0.011). On the other hand, higher age (HR=1.01, 95%CI=1.00–1.02, P<0.001) and concomitant GC (HR=1.29, 95%CI=0.47–0.61, P<0.001) increased drug discontinuation due to toxic adverse events. Adjusted by potential confounders, aIL-6R showed lowest discontinuation due to lack of effectiveness, and CTLA4-Ig showed lowest discontinuation due to toxic adverse events. Besides the difference of bDMARDs and JAKi, concomitant GC increased drug discontinuation due to lack of effectiveness and toxic adverse events. [1]Ebina K, et al. Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis-the ANSWER cohort study. Arthritis Res Ther. Apr 11 2019;21(1):91. [2]Ebina K, et al. Drug retention of 7 biologics and tofacitinib in biologics-naive and biologics-switched patients with rheumatoid arthritis: the ANSWER cohort study. Arthritis Res Ther. Jun 15 2020;22(1):142. [3]Ebina K, et al. Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study. Sci Rep. Jan 7 2022;12(1):134. NIL. Kosuke Ebina Speakers bureau: AbbVie, Amgen, Asahi-Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Pfizer, Sanofi, Taisho, and UCB Japan., Consultant of: Asahi-Kasei and Taisho., Grant/research support from: AbbVie, Asahi-Kasei, Eisai, Mitsubishi-Tanabe, and Teijin Pharma. Affiliated with the Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, which is supported by Taisho., Yuki Etani Grant/research support from: Eli Lilly, Yuichi Maeda Speakers bureau: Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol Myers Squibb, and Mitsubishi Tanabe Pharma Corporation, Grant/research support from: Eli Lilly, Yasutaka Okita Speakers bureau: Chugai Pharmaceutical, Pfizer, and Ono, Makoto Hirao Speakers bureau: Astellas, Ono Pharmaceutical, Eli Lilly, Mitsubishi-Tanabe, Pfizer, Ayumi, and Takeda, Wataru Yamamoto: None declared, Motomu Hashimoto Speakers bureau: Mitsubishi-Tanabe, Eisai, Eli Lilly, Bristol-Myers Squibb, and Novartis Pharma, Grant/research support from: Mitsubishi-Tanabe, Eisai, Eli Lilly, Bristol-Myers Squibb, and Novartis Pharma, Koichi Murata Speakers bureau: AbbVie GK, Eisai Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Bristol-Myers Squibb, Daiichi Sankyo Co. Ltd., and Asahi Kasei Pharma Corp., Grant/research support from: Daiichi Sankyo, Ryota Hara Speakers bureau: AbbVie and Eisai, Koji Nagai: None declared, Yuri Hiramatsu: None declared, Yonsu Son: None declared, Hideki Amuro: None declared, Takayuki Fujii Speakers bureau: Asahi Kasei Pharma, Abbvie, Jansen, Tanabe Mitsubishi Pharma, and Eisai, Takaichi Okano: None declared, Yo Ueda: None declared, Masaki Katayama: None declared, Tadashi Okano Speakers bureau: Abbvie, Chugai, Eli Lilly, Janssen and Novartis Pharma., Grant/research support from: Abbvie, Asahi Kasei, Chugai, Eisai, Eli Lilly and Tanabe Mitsubishi., Atsushi Kumanogoh Speakers bureau: Chugai, Eisai, Tanabe-Mitsubishi, Abbvie, and Ono, Grant/research support from: Chugai, Seiji Okada: None declared, Ken Nakata Grant/research support from: Astellas. [Display omitted]

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Adverse events / Biological products / Cohort analysis / CTLA-4 protein / Cytotoxicity / Disease-modifying Drugs (DMARDs) / Enzyme inhibitors / Immunoglobulins / Interleukin 6 / Interleukin 6 receptors / Janus kinase / Lymphocytes T / Malignancy / Methotrexate / Patients / Pharmaceuticals / Real-world evidence / Regenerative medicine / Remission / Remission (Medicine) / Retention / Rheumatoid arthritis