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

Authors

Victoria Allen, Mark Gibson, Maryam Adas, Rohan Chavali, Leigh De Gracia, Hassan Hussain, Iman Muzafar, Samaad Muzafar, Nithya Suresh, Youngsung Yoon, Katie Bechman, Jeremy Brown, Mark Russell, Anna L Goodman, Sinead M Langan, Sam Norton, David Phillippo, Nicky Welton, James Galloway

Published in

The Journal of infection. Pages 106864. Sep 23, 2026. Epub Sep 23, 2026.

Abstract

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.
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).
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.
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.

PMID:
42777833
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.

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