AB0548 STUDY OF CLINICAL EFFICACY AND JOINT DESTRUCTION INHIBITORY EFFECTS OF FIVE JAK INHIBITORS
Authors: T. Kawahata, K. Katayama, T. Okubo, Y. Nakino, K. Tanaka, T. Sato, S. Abe, H. Ito
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> There are hardly any reports that comprehensively examine the clinical efficacy and joint destruction inhibitory effects of the five JAK inhibitors used in the treatment of Rheumatoid Arthritis (RA). <h3>Objectives:</h3> To investigate the clinical efficacy and joint destruction inhibitory effects of the five JAK inhibitors: Tofacitinib (TOF) in 30 cases, Baricitinib (BARI) in 53 cases, Peficitinib (PEF) in 27 cases, Upadacitinib (UPA) in 41 cases, and Filgotinib (FIL) in 38 cases, totaling 189 cases. <h3>Methods:</h3> Clinical efficacy was assessed based on the treatment improvement effects using DAS28-ESR, DAS28-CRP, Patient-VAS, Pain-VAS, Doctor-VAS before and three months after drug administration, as well as the effectiveness rate in patients resistant to csDMARDs, tsDNMARDs, and b-DMARDs. The progression of joint destruction in the wrist or finger joints of the hands was examined using the mTSS method on X-rays before and one year after administration, in cases with extensive bone marrow edema observed in MRI (1.5T, Toshiba) at the same location[1]. The progression of joint destruction in medium and large joints was examined in a similar manner to small joints, using X-rays(Larsn grade)in cases with extensive bone marrow edema positivity. Paired T test was used for statistical significance. <h3>Results:</h3> Clinical efficacy showed almost similar improvement across all five groups (Table 1). However, differences were observed in the joint destruction inhibitory effects between formulations (Table 2). In TOF and UPA, the inhibitory effect on medium and large joint destruction was lower. This could be due to TOF being the first JAK inhibitor with a high occurrence of D2TRA, inclusion of joints like the hip joint that are prone to progress, and lower MTX intake in UPA. Conversely, FIL's high frequency of MTX use and evidence of RRP inhibitory effect[2] were thought to contribute to its progression inhibition. Additionally, in BARI, the effectiveness in improving RRP cases that occurred in UPA and PEF was demonstrated. This analysis indicated a need for further multi-institutional studies due to the small number of cases and differences in the background of each drug (MTX usage frequency, and the proportion of patients resistant to b-DMARDs and ts-DMARDs). Also, the short duration of the clinical efficacy study period of three months was considered a limitation that warrants further investigation. <h3>Conclusion:</h3> While the clinical improvement effects of the five JAK inhibitors were almost equivalent, differences were observed in joint destruction inhibitory effects, especially in medium and large joints, among the drugs. <h3>REFERENCES:</h3> [1] Cole1batch AN, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013; 72:804–14 [2] Tanaka Y et al. Post Hoc Analysis o Two TrialsBenefit of Filgotinib, a JAK1 Preferential Inhibitor, in Rheumatoid Arthritis Patients with Previous Rapid Radiographic Progression: Post Hoc Analysis of Two Trials. Rheumatoid Ther https://doi.org/10.1007//s40744-022-00503-3 <b>Table 1.</b> Baseline demographics and clinical improvement in five JAK inhibitors. Paired T test; **P&lt;0.01, *P&lt;0.05 <b>Table 2.</b> Inhibitory effect on small joints and medium and large joints in five JAK inhibitors. Paired T test; **P&lt;0.01, *P&lt;0.05 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>