Impact of drug-drug interaction of JAK inhibitors, CYP enzyme inhibitors and OAT3 inhibitors on persistence and infection rates in patients with autoimmune rheumatic diseases.

OBJECTIVES

Janus kinase (JAK) inhibitors are effective treatments for autoimmune rheumatic diseases (AIRDs). However, concomitant use of JAK inhibitors with CYP enzyme inhibitors or OAT3 inhibitors can lead to drug-drug interactions. This study aimed to evaluate the impact of the concomitant use of CYP and OAT3 inhibitors on discontinuation of treatment and infectious complications in patients treated with JAK inhibitors.

METHODS

Using the National Health Insurance Research Database, this retrospective cohort study included patients with rheumatoid arthritis, psoriatic arthritis and atopic dermatitis treated with JAK inhibitors in 2021-2023. The risks of discontinuation of treatment and infectious complications were evaluated using Cox proportional hazards models, adjusted for age, gender, other infectious and concomitant use of steroids or methotrexate.

RESULTS

Among 7591 patients, concomitant use of strong CYP3A4, or CYP2C19 inhibitors increased the risk of treatment discontinuation for tofacitinib and baricitinib from 41% to 144%. The risk of overall infectious complications also increased when tofacitinib was used concomitantly with strong CYP2C19 inhibitors. The risk of pneumonia was further increased by concomitant use of strong CYP2C19 inhibitors with all JAK inhibitors and CYP3A4 inhibitors with tofacitinib. The risk of urinary tract infection was increased by concomitant use of strong CYP2C19 inhibitors when used with tofacitinib, or baricitinib.

CONCLUSIONS

Concomitant use of strong CYP3A4, and CYP2C19 inhibitors with JAK inhibitors significantly increases the risk of discontinuation of treatment and infectious complications in patients with AIRDs. Careful consideration of drug-drug interactions is necessary when prescribing JAK inhibitors to optimize treatment persistence and minimize adverse events.