Pos0840 the difference in creatine kinase elevation caused by jak inhibitors and il-6 inhibitors in rheumatoid arthritis

Background Cases of creatine kinase (CK) elevation caused by Janus kinase inhibitor (JAKi) treatment for rheumatoid arthritis (RA) have been reported in clinical trials[1]. IL-6 signals via the JAK-STAT pathway. However, it is not known whether the CK elevation is due to JAKi alone or to IL-6 inhibitor (IL-6i) as well. Objectives The objective was to examine whether the CK elevation is specific to JAKi therapy or similar to IL-6i therapy by propensity score (PS)-matching. Methods A multicenter database of JAKi (n=168) and IL-6i (n=113) treatment was used. All cases were followed-up at 24 weeks, and their CK levels were evaluated. A total of 71 cases in each group were extracted by the PS-matching method (using age, sex, BMI, and CK at 0 weeks (W)). The percentage abnormal from the standard titer was compared for the JAKi and IL-6i groups. The factors related to an elevated CK at 24 weeks were investigated using patients’ background characteristics at the time of starting treatment by univariate analysis. Results The patients’ median age was 66 years, CK at 0W was 57I U/L, and mean BMI was 22.5 kg/m2. There were no significant differences between the groups at the time of starting treatment (Table 1). The changes in CK by JAKi and IL-6i treatments are shown in the Figure 1. The CK at 4W with JAKi treatment was significantly higher than that with IL-6i treatment (83 vs 72 IU/L; P=0.018). The same tendency was seen at 12W and 24W. The outlier rate (Grade 1: 1 < titer < 2.5 times) with JAKi treatment increased significantly over time (0W: 4.2%, 4W: 18.1%, 12W: 21.7%, 24W: 18.3%, P=0.015), whereas that with IL-6i treatment increased slightly (0W: 5.6%, 4W: 9.2%, 12W: 8.6%, 24W: 8.5%, P=0.745), with a significant difference between the groups (P=0.035). Of all the patients, only three showed Grade 2 (2.5 < titer < 5 times). No RA patients discontinued treatment due to myalgia or renal dysfunction. The factors significantly positively related to elevated CK at 24W were male and creatine, and those significantly negatively related were stage, class, mHAQ, eGFR, and PSL dosage. Conclusion CK elevation was greater with JAKi treatment at 4W and maintained until 24W than with IL-6i treatment in RA patients with adjustment for background characteristics. The CK elevation might be specific to JAKi treatment. The mechanism needs to be clarified in the future. Reference [1]Fleischmann, R. et al. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis & rheumatology (Hoboken, N.J.) 71, 1788-1800, doi:10.1002/art.41032 (2019). Acknowledgements: NIL. Disclosure of Interests None Declared.