Tuberculosis during JAK inhibitor or TNF-α inhibitors therapy: a disproportionality analysis from WHO pharmacovigilance database

Small-molecule oral Janus kinase (JAK) inhibitors are increasingly used for treatment of digestive and rheumatic inflammatory diseases or haematological disorders. Based on limited data, the risk of tuberculosis (TB) has been reported but considered lower compared with that observed with TNF-α inhibitors a finding we propose to clarify using the WHO VigiBase pharmacovigilance database. We performed a disproportionality analysis of drug-related TB infection using VigiBase. An information component 0.25 (IC0.25) >0 was considered statistically significant. Data were extracted on 09/12/2024. Main characteristics of patients with respiratory infection under JAK and TNF-α inhibitors were analysed. Globally, the mean IC0.25 for TB was 2.0 and 3.2 for JAK and TNFα inhibitors, respectively. Among JAK inhibitors, the risk of TB varied and appeared significant for ruxolitinib, baricitinib, tofacitinib and upadacitinib. A total of 695 patients with TB occurring during JAK inhibitor therapy were included. We observed a higher proportion of reported cases among women (54.7%), aged from 45 to 64 years (35.7%). Extra-thoracic TB involvements were reported in 133 cases (66%). TB cases were most frequently reported among patients receiving tofacitinib (n=330, 47.5%), ruxolitinib (n=217, 31.1%) and upadacitinib (n=102, 14.6%). Overall, 42 patients (5.9%) died with active TB. JAK inhibitors are associated with an increased risk of TB. These results argue to recommend latent TB infection screening and systematic anti-TB preventive therapy even in low endemic countries, before initiating JAK inhibitor therapy.