Safety of Janus kinase inhibitors compared to biologic therapy in patients with inflammatory bowel disease

There is a paucity of data regarding the comparative safety of Janus kinase inhibitors (JAKi) compared to biologic therapy in inflammatory bowel disease (IBD).

A retrospective cohort study was conducted using the U.S. Collaborative Network to assess the risk of adverse events in patients with IBD on JAKi compared to biologic therapies (tumor necrosis factor inhibitor, ustekinumab or vedolizumab). Outcomes assessed included infections, major adverse cardiovascular events (MACE), malignancy, venous thromboembolism (VTE), gastrointestinal perforations and laboratory abnormalities within 2 years. 1:1 propensity score matching (PSM) was performed.

There were 3,186 patients in the JAKi cohort (mean age 44.3 ± 17.1, 46.5% male sex, 85.7% ulcerative colitis, 72% tofacitinib) and 60,462 patients in the biologic cohort. After PSM, there was no difference in the risk of bacterial (adjusted odds ratio [aOR], 1.08; 95% confidence interval [CI], 0.82-1.43), viral (aOR, 1.06; 95% CI, 0.84-1.32), or fungal infections (aOR, 1.10; 95% CI, 0.84-1.44), MACE (aOR, 0.72; 95% CI, 0.47-1.10), malignancy (aOR, 0.98; 95% CI, 0.71-1.35), and VTE (aOR, 0.95; 95% CI, 0.67-1.34). This was consistent in subgroup analyses based on IBD type, JAKi type and age group. There was a higher risk of low-density lipoprotein ≥ 190 mg/dL (aOR, 1.78; 95% CI, 1.03-3.05) and grade 3 or higher lymphopenia (aOR, 2.28; 95% CI, 1.60-3.26) in the JAKi cohort. There was no difference in the 4-year risk of MACE or malignancy in the tofacitinib cohort compared with the biologic cohort.

Our real-world study did not show an increased risk of adverse events except severely elevated LDL and lymphopenia in patients on JAKi compared to biologic therapy.