Original Research
Tuesday, November 14, 2023
08:30 AM–10:00 AM
Abstract
Introduction:
Janus kinase inhibitors (JAKi), types of immunomodulatory drugs, are primarily metabolized by cytochrome P450 (CYP) enzymes, which are important determinants of drug interactions.
Research Question or Hypothesis:
This study aimed to estimate the adverse events (AEs) among patients treated with JAKi with or without drug interaction.
Study Design:
This is a retrospective observational study using a multi-institutional electronic medical database.
Methods:
Patients newly received JAKi from January 2015 to April 2022 and had at least one clinic visit during the past year were included. During JAKi treatment, patients with more than one day of overlapping any interacted medication were defined as the drug-interaction group. Drug interaction severity and possible AEs were further assessed using the Lexicomp database. Based on the database, medications causing drug-drug interactions were classified into CYP enzyme moderate inhibitors, weak inhibitors, and no drug-drug interaction groups. Eligible patients were tracked for a year to monitor potential AEs, including embolism and thrombosis, musculoskeletal tissue disorders, neutropenia, and thrombocytopenia. These AEs were identified by examining levels of D-dimer, creatinine kinase (CK), white blood cell (WBC) counts, and platelet counts, respectively, from patients' laboratory data.
Results:
A total of 1208 patients (251 in baricitinib, 856 in tofacitinib, and 101 in the upadacitinib group) were included in this study, and 24% (n=290) reported AEs. Overall, 74.3% (n=898) were female, with an average age being 55.0 (SD: 15.0). The results showed the combination of JAKi and CYP enzyme inhibitors was associated with a significantly increased risk of higher D-dimer levels (odds ratio [OR]: 4.70, 95%confidence interval [C1]:1.03-21.3), whereas those of higher CK levels (OR: 2.85, 95% CI: 0.64-12.7), decreased WBC counts (OR 2.90; 95% CI: 0.94-8.92), and decreased platelet levels (OR 1.97; 95% CI: 0.56-6.89) were relatively insignificant.
Conclusion:
This study demonstrated that patients being treated together with JAKi and CYP enzyme inhibitors were associated with an increased risk of AEs.
Presenting Author
Wei-Ting Lee Pharm DLinKou Chang Gung Memorial Hospital
Authors
Kai-Cheng Chang PHD student
Linkou Chang Gung Memorial Hospital
Hui-Yu Chen MS
Linkou Chang Gung Memorial Hospital