Masahiro Tada1, Tadashi Okano2, Kenji Mamaoto2, Yutaro Yamada2, Kazuki Orita3, Koji Mandai4, Shohei Anno3, Takahiro Iida5, Kentaro Inui4, Tatsuya Koike6

1Department of Orthopaedic Surgery, Osaka City General Hospital, Osaka, Japan
2Department of Orthopaedic Surgery, Osaka Metropolitan University Medical School, Osaka, Japan
3Department of Orthopaedic Surgery, Yodogawa Christian Hospital, Osaka, Japan
4Department of Orthopaedic Surgery, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
5Department of Orthopaedic Surgery, Koryokai Hospital, Osaka, Japan
6Shirahama Foundation For Health and Welfare, Search Institute For Bone and Arthritis Disease (sinbad), Wakayama, Japan

Keywords: Creatine kinase, Il-6 inhibitor, JAK inhibitor, multicenter observational study, rheumatoid arthritis.


Objectives: This study aimed to examine whether creatine kinase (CK) elevation occurs with interleukin (IL)-6 inhibitors, as in Janus kinase (JAK) inhibitors, which are reported to increase CK levels in rheumatoid arthritis.

Patients and methods: A multicenter database of JAK inhibitor and IL-6 inhibitor treatment was retrospectively searched between January 2016 to December 2022; 142 cases (117 females, 25 males, mean age: 63.8±13.0 years; range, 20 to 85 years), with 71 cases in each group, were extracted by propensity score matching using age, sex, body mass index, and CK at 0 weeks. The outlier rate was compared. Patients’ background characteristics related to elevated CK levels at 24 weeks were investigated by univariate and multivariate analyses.

Results: Creatine kinase levels at 4 and 12 weeks were significantly higher with JAK inhibitors than with IL-6 inhibitors (four weeks, 72 vs. 87.5 IU/mL, p=0.016; 12 weeks, 71 vs. 95.5 IU/mL, p=0.028). The outlier rate (Grade 1) with JAK inhibitors increased significantly over time (0 weeks, 4.2%; four weeks, 18.1%; 12 weeks, 21.7%; 24 weeks, 18.3%; p=0.015), whereas that with IL-6 inhibitors increased slightly (0 weeks, 5.6%; four weeks, 9.2%; 12 weeks, 8.6%; 24 weeks, 8.5%; p=0.745), with a significant difference between the groups (p=0.035). No patients discontinued treatment due to myalgia or renal dysfunction. The factors significantly positively related to elevated CK levels at 24 weeks were male sex and creatinine. Those significantly negatively related were Steinbrocker stage and class, modified health assessment questionnaire scores, estimated glomerular filtration rate, and glucocorticoid dose.

Conclusion: Mild CK elevations with JAK inhibitors are not a particular clinical problem. CK elevation might be specific to JAK inhibitors.

Citation: Tada M, Okano T, Mamaoto K, Yamada Y, Orita K, Mandai K, et al. Comparison of creatine kinase elevation caused by Janus kinase inhibitors and interleukin-6 inhibitors in patients with rheumatoid arthritis: A propensity score-matched study. Arch Rheumatol 2024;39(x):i-viii. doi: 10.46497/ArchRheumatol.2024.10645.