SAT0057 PREDICTING INADEQUATE RESPONSE TO JAK INHIBITORS BY CLUSTER ANALYSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: M. Sugawara, Y. Fujieda, A. Noguchi, S. Tanimura, Y. Shimizu, I. Nakagawa, M. Kono, M. Kato, K. Oku, T. Atsumi
Journal: Annals of the Rheumatic Diseases (2020)

Background: Oral Janus kinase inhibitors (JAKi) have dramatically altered outcomes in patients with rheumatoid arthritis (RA). However, there remains some proportion of patients who respond to inadequately JAKi treatment (JAKi-IR) [1,2]. The characteristics in RA patients associated with JAKi-IR have not been fully demonstrated. Objectives: To clarify the characteristics of JAKi-IR in patients with RA by cluster analysis. Methods: This retrospective study comprised 120 RA patients who were treated with JAKi (Tofacitinib or Baricitinib) between July 2013 and September 2019 in five facilities. The disease status at the baseline, at 12 weeks after JAKi treatment and at the time point of withdrawing JAKi was assessed using the Disease Activity Score (DAS28) and the American College of Rheumatology (ACR) response criteria. JAKi-IR was defined as follows, primary non-response at 12 weeks after JAKi treatment: withdrawal of JAKi with ACR20 non-response or non-improvement in DAS28-CRP (ΔDAS28-CRP&lt;1.2 from baseline), secondary non-response: withdrawal of JAKi without clinical remission after 12 weeks. Hierarchical cluster analysis was performed with the following variables: gender, age, disease duration, bone erosion, ACR functional classification (Class ≥3), comcomitant rheumatoid arthritis related interstitial lung disease (RA-ILD) or other autoimmune disease (AID), anti-citrullinated protein antibody (ACPA) positivity, rheumatoid factor (RF) at baseline, use/dose of methotrexate (MTX) and prednisolone (PSL), serum ESR/CRP, tender/swollen joint counts (TJC/SJC), visual analog scale by patients (VAS-Pt), and prior of biologic DMARDs. Results: The 120 enrolled patients were classified into 4 groups by cluster analysis(Figure1), The characteristics of each group are as follows, Group A(n=21): female + bone erosion + RF/ACPA positive + AID + MTX non-user, Group B(n=36): male + older age + RA-ILD + RF/ACPA positive + MTX non-user, Group C(n=35): RF/ACPA positive + absence of RA-ILD + MTX user, Group D (n=28): seronegative + MTX user + absence of RA-ILD + history of biologic DMARDs failure. The rate of JAKi-IR was A:9%, B:8%, C:20%, D:32%, and the significant difference between Group B and D was identified (p=0.02). In multiple comparison of 4 groups, no significant difference was identified (p=0.06) (Figure2). Conclusion: JAKi-IR would be more likely to be seronegative, MTX use, absence of RA-ILD and history of biologic DMARDs failure. Cluster analysis is an exploratory tool that aids in the analysis of huge amount of data. References: [1] Takeuchi T, Yamanaka H, Yamaoka K, Arai S, Toyoizumi S, DeMasi R, et al. Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: A post hoc analysis of clinical trial data. Mod Rheumatol. 2019;29(5):756-66. [2] Tanaka Y, Atsumi T, Amano K, Harigai M, Ishii T, Kawaguchi O, et al. Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials. Mod Rheumatol. 2018;28(4):583-91. Disclosure of Interests: Masanari Sugawara: None declared, Yuichiro Fujieda: None declared, Atsushi Noguchi: None declared, Shun Tanimura: None declared, Yuka Shimizu: None declared, Ikuma Nakagawa: None declared, Michihito Kono: None declared, Masaru Kato: None declared, Kenji Oku: None declared, Tatsuya Atsumi Grant/research support from: Eli Lily Japan K.K., Alexion Pharmaceuticals, Inc., Bristol-Myers Squibb Co., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Consultant of: Gilead Sciences, Inc., Eli Lilly Japan K.K., UCB Japan Co. Ltd., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Speakers bureau: Eli Lilly Japan K.K., UCB Japan Co. Ltd., Bristol-Myers Squibb Co., AbbVie Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc.