Comparative serious infection and sepsis risks with advanced therapies in IMIDs: a Bayesian network meta-analysis.

OBJECTIVES: Evidence on serious infection (SI)-risk with advanced therapies across immune-mediated inflammatory diseases (IMIDs) is limited. We compared SI- and sepsis-rates within a global-IMID network and assessed whether these are consistent across IMIDs. METHODS: We included studies evaluating advanced therapies across four networks: rheumatoid arthritis (RA), psoriasis/psoriatic arthritis (Pso/PsA), inflammatory bowel disease (IBD) and a global-IMID network. We used a Bayesian framework to present SI- and sepsis-rates as rate-ratios (RR) and 95% credibility intervals (CrI). RESULTS: 261 studies providing 86,844 person-years-of-exposure were included. In the global-network, JAK-inhibition was associated with a greater SI-rate than control, (placebo/methotrexate), (RR 1.44, 95% CrI 1.12-1.89, posterior probability (pp) >99%), corresponding to 2.1 additional SI-events per 100-PYE in high-risk populations (95% CrI 0.6-4.3). JAK-inhibition was associated with greater SI-rate than TNF-inhibition (RR 1.34, 95% CrI 1.00-1.81, pp 97.3%). TNF-inhibition was associated with lower sepsis-rate than control (RR 0.54, 95% CrI 0.30-0.99, pp 98%). CTLA4-inhibition in RA (RR 0.81 vs control, 95% CrI 0.54-1.19, pp 87%) and IL-23-inhibition in Pso/PsA and IBD were ranked safest. CONCLUSIONS: Across IMIDs, JAK-inhibition carries higher SI-risk than TNF-inhibition and control. Treatment selection should integrate both drug- and IMID-specific risks. The association between TNF-inhibition and reduced sepsis-risk warrants further investigation.