Adverse reactions to Janus kinase inhibitors: Study of their incidence and predictive factors in patients with rheumatoid arthritis

Background and objective

The safety profile of Janus kinase (JAK) inhibitors has acquired attention due to post-marketing observed adverse drug reactions. The study focuses on the analysis of adverse reactions related to tofacitinib, baricitinib, upadacitinib, and filgotinib in rheumatoid arthritis patients, including identifying predictive factors linked to their occurrence.

Patients and methods

Observational retrospective study. Adult patients with rheumatoid arthritis from a university hospital receiving JAK inhibitor treatment between September 2017 and January 2024 were included. The cumulative incidence of each adverse reaction was calculated using the Naranjo scale. Risk factors for developing adverse reactions were identified through logistic regression analyses.

Results

Two hundred twenty-three patients were included, with 28.7% presenting adverse reaction related to JAK inhibitor treatment. The adverse drug reactions with the highest cumulative incidence were infections and gastrointestinal disorders. Infections included: upper respiratory tract (4.5%), cellulitis (3.1%), urinary tract (2.7%), herpes zoster (1.8%). Gastrointestinal disorders comprised: abdominal pain (4.0%), diarrhea (3.6%), nausea and vomiting (3.6%), gastrointestinal perforation (1.3%), diverticulitis (0.9%). Classified at 0.5% were: headache, paresthesias, skin rash, severe neutropenia, insomnia, dyspnea, hypertensive crisis. As risk factors, were identified: the treatment with a non-selective JAK inhibitor (OR adjusted: 4.03; 95% CI: 1.15–14.10; P = 0.029) and older age (OR adjusted: 1.03; 95% CI: 1.00–1.05; P = 0.036).

Conclusions

Infections and gastrointestinal disorders represented the adverse reactions related to JAK inhibitor treatment with the highest cumulative incidence, with risk factors for their occurrence being non-selective JAK inhibitor treatment and older age of the patient.