The Journal of infection · 2026
Comparative serious infection and sepsis risks with advanced therapies in IMIDs: a Bayesian network meta-analysis.
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Allen Victoria, Gibson Mark, Adas Maryam, Chavali Rohan, De Gracia Leigh, Hussain Hassan, Muzafar Iman, Muzafar Samaad, Suresh Nithya, Yoon Youngsung, Bechman Katie, Brown Jeremy, Russell Mark, Goodman Anna L, Langan Sinead M, Norton Sam, Phillippo David, Welton Nicky, Galloway James
Аннотация
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.
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.