Comparative serious infection and sepsis risks with advanced therapies in IMIDs: a Bayesian network meta-analysis
In brief
JAK inhibitors had 44% higher serious infection rates than control
Across 261 studies and 86,844 person-years, JAK inhibitors were linked to a 44% higher serious infection rate than placebo or methotrexate, and a 34% higher rate than TNF inhibitors. In high-risk populations, that amounted to 2.1 additional infections per 100 person-years; treatment choices still need to account for disease-specific risks, and the apparent lower sepsis rate with TNF inhibitors needs more study.
- Journal
- The Journal of infection (Q1)
- Published
- 23 September 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Victoria Allen, Mark Gibson, Maryam Adas, Rohan Chavali, Leigh De Gracia, Hassan Hussain, et al.
- PMID
- 42777833
- DOI
- 10.1016/j.jinf.2026.106864
Why clinicians should know about it
- Picked for Rheumatology (paper of the day, 25 September 2026): Network meta‑analysis of serious infection risk with advanced therapies
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.