Safety Profile of Tofacitinib in a Single-Center Real-World Cohort: A Comprehensive Analysis of Adverse Events and Associated Risk Factors

Background and aimTofacitinib, an oral Janus kinase (JAK) inhibitor, has significantly changed the treatment landscape of inflammatory arthritis.Real-world safety data on tofacitinib regarding serious infections, major adverse cardiovascular events (MACE), and malignancies are less common.This study aimed to describe the incidence of significant adverse events (AEs) and identify baseline and treatment-related factors associated with these outcomes in a routine clinical setting. MethodsThis was a single-center observational study conducted at the Department of Rheumatology, Divisha Arthritis and Medical Center, Bengaluru, India.The study included 1,000 adult patients with inflammatory arthritides who received tofacitinib and had documented safety follow-up.Patients who received tofacitinib for various types of arthritis from January 2022 to January 2024 (two years) were observed.Patients were selected using consecutive sampling based on predefined eligibility criteria.Safety endpoints included tuberculosis (TB), MACE, stroke, herpes zoster (HZ), cytopenia, GI issues, and malignancy.Fisher's exact test was used for univariate screening, and multivariable logistic regression was used to identify independent predictors and calculate adjusted ORs (aORs). ResultsThe most frequently observed AEs were TB (21 (2.1%)), HZ (15 (1.5%)), GI issues (13 (1.3%)), and cytopenia (10 (1.0%)).Cardiovascular events were rare, with three strokes (0.3%) and two MACE events (0.2%); notably, no malignancies were reported in the dataset.Significant independent risk factors for TB included prior TB risk (aOR, 38.2), prior tumor necrosis factor inhibitor use (aOR, 3.1), and prior steroid use (aOR, 2.8).Smoking was significantly associated with MACE (p = 0.0463).The small number of stroke events precluded reliable multivariable assessment of factors associated with stroke. ConclusionsThe safety profile was consistent with known JAK inhibitor mechanisms, but the high TB incidence in this endemic region emphasizes the need for a layered risk assessment.Rigorous screening for latent TB, aggressive management of metabolic risks such as diabetes, and cardiovascular risk stratification are essential to optimize the benefit-risk balance of tofacitinib.