Pos0673 the Comparative Observational Study About Efficacy, Safety and Drug Survival Rate of Janus Kinase Inhibitors Between Difficult-to-Treat Rheumatoid Arthritis (D2tra) and Non-D2tra

Background: Although the remission rate of RA has increased dramatically with the application of targeted therapies, such as biologic agents or Janus kinase inhibitors (JAKi) in combination with methotrexate. D2TRA, defined as patients having active disease with failure of at least two biological or targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) with different mechanisms of action, occurs in about 5-10% of RA patients. The physical and economic burden on patients is significant, and effective treatment for D2TRA needs to be investigated. Objectives: To compare the efficacy, safety, and drug survival rate of JAKi between the D2TRA and non-D2TRA groups. Methods: This study was conducted in one hundred and eighteen patients with RA treated with JAKi at Saitama Medical University Hospital between Oct. 2014 and Nov. 2023. All patients fulfilled the 1987 or 2010 classification criteria for RA. The patients were divided into two groups; D2TRA (n=56) fulfilling of the EULAR DT2RA definition and non-D2TRA (n=62), and retrospectively observed for 12 months. We compared the baseline characteristics, disease activity, drug continuation rate, and adverse events between the two groups. Results: In background, there were no significant differences in age at initiation of JAKi, the percentage of female patients, duration of RA, tender joint counts, swollen joint counts, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score of 28 joints (DAS28), rheumatoid factor (RF) positivity, anti-cyclic citrullinated peptide (CCP) antibody positivity, frequency of corticosteroid use, and methotrexate use between the two groups. The patients with a history of JAKi use were 39.3% in the D2TRA group and 8.1% in the non-D2TRA group. In both the D2TRA and the non-D2TRA group, DAS28-CRP showed decrease from baseline until 12 weeks after starting JAKi therapy. The median DAS28-CRP decreased from 4.21 to 3.18 (p=0.012) in the D2TRA group and from 3.95 to 2.17 (p<0.001) in the non-D2TRA group. The rate of patients in remission and low disease activity at the start of treatment and after 12 weeks of treatment increased from 10.7% to 43.2% in the D2TRA group and from 22.2% to 60.6% in the non-D2TRA group. Among patients in the D2TRA group who had previously failed treatment with JAKi, the rate of patients in remission and low disease activity at 12 weeks was 21.4%. There was no significant difference in the drug survival rate for 12 months between the D2TRA and the non-D2TRA (57.1% vs. 59.7%). JAKi therapy was discontinued due to adverse events in 21% of the D2TRA versus 23% of the non-D2TRA group, with the difference not being significant. Patients who discontinued the drug due to lack of efficacy were 21% in D2TRA and 18% in non-D2TRA group. Conclusion: Based on the results of our real-world clinical study, JAKi was effective for D2TRA, with safety and drug survival rates comparable to non-D2TRA. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: MAYUMI MATSUDA: None declared, Yu Funakubo Asanuma: None declared, Takuma Tsuzuki Wada: None declared, Yuji Akiyama: None declared, Yasuto Araki: None declared, Kazuhiro Yokota: None declared, Hiroshi Kajiyama: None declared, Toshihide Mimura Pfizer Japan, Gilead Sciences.