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AB0387 (2022)
THE RELATIONSHIP BETWEEN JAK INHIBITORS AND CREATINE KINASE ELEVATION IN PATIENTS WITH RHEUMATOID ARTHRITIS: A REAL-WORLD CLINICAL STUDY
M. Tada1, T. Okano2, K. Mamoto2, Y. Yamada2, K. Orita3, K. Mandai4, S. Anno2, T. Iida5, K. Inui4, T. Koike6
1Osaka City General Hospital, Orthopaedic Surgery, Osaka, Japan
2Osaka City University Medical School, Orthopaedic Surgery, Osaka, Japan
3Yodogawa Christian Hospital, Orthopaedic Surgery, Osaka, Japan
4Osaka Saiseikai Nakatsu Hospital, Orthopaedic Surgery, Osaka, Japan
5Koryokai Hospital, Orthopaedic Surgery, Osaka, Japan
6Osaka City University Medical School, Center for Senile Degenerative Disorders (CSDD), Osaka, Japan

Background: Some cases of creatine kinase (CK) elevation caused by Janus kinase (JAK) inhibitor treatment for rheumatoid arthritis (RA) have been reported in clinical trials 1 . However, the frequency and patients’ background characteristics in clinical practice are unknown.


Objectives: The correlation between JAK inhibitor treatment for RA and changes in CK levels in clinical practice were investigated using a multicenter database.


Methods: The multicenter database of JAK inhibitors was used, and 103 (tofacitinib 46, baricitinib 44, upadacitinib 11, peficitinib 1, filgotinib 1) of 265 RA patients were followed up at 24 weeks, and their CK levels were evaluated. The time-dependent change of CK was evaluated by sex and analyzed by the Wilcoxon signed-rank test. The percentage abnormal from the standard titer was calculated. The factors related to an elevated CK at 24 weeks were investigated using patients’ background characteristics at the time of starting JAK inhibitors by univariate analysis.


Results: Women accounted for 85.4% of the patients, the median age was 68 years, disease duration was 15 years, and the mean DAS28ESR was 5.00. The CK levels of both men and women were significantly elevated at 4 weeks and maintained until 24 weeks (men, women: 63, 62 (0 weeks), 101, 95 (4 weeks), 119, 96 (12 weeks), 155, 99 (24 weeks), U/L, P<0.001) ( Figure 1 ). The percentage abnormal was also significantly increased at 4 weeks and maintained until 24 weeks (5.8% (0 weeks), 20.7% (4 weeks), 26.3% (12 weeks), 24.3% (24 weeks), P=0.002). The factors significantly positively related to elevated CK levels at 24 weeks were male, CK, creatinine, and lactate dehydrogenase (LDH), and stage, class, modified health assessment questionnaire, estimated glomerular filtration rate (eGFR), and glucocorticoid use were significantly negatively correlated ( Table 1 ). There were no significant differences in CK elevation among the agents.

Characteristics at the time of starting JAK inhibitors related to elevated creatine kinase levels at 24 weeks

Univariate
Data at stating JAK inhibitors R value P value
Creatine kinase 0.653 <0.001
Gender, men 0.247 0.012
Steinbrocker stage -0.215 0.039
Steinbrocker class -0.277 0.008
modified health assessment questionnaire -0.268 0.008
Creatinine 0.289 0.003
eGFR -0.231 0.019
LDH 0.201 0.041
Glucocorticoid use -0.409 0.008

Analyzed by Spearman rank correlation coefficient

Time-dependent changes of CK in all RA patients


Conclusion: CK was significantly elevated at 4 weeks and maintained until 24 weeks. However, no patients complained of muscle pain and stopped JAK inhibitors. Patients with high CK, low eGFR, high LDH, or maintained activities of daily living at the time of starting JAK inhibitors tended to have high CK levels at 24 weeks.


REFERENCES:

[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).


Disclosure of Interests: None declared

Citation: , volume 81, supplement 1, year 2022, page 1321
Session: Rheumatoid arthritis - non biologic treatment and small molecules (Publication Only)