Clin Gastroenterol Hepatol. 2026 Oct 31:S1542-3565(26)00819-0. doi: 10.1016/j.cgh.2026.10.017. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: Data on the safety of newer advanced therapies (AT) for immune-mediated inflammatory diseases (IMIDs) remain limited in older patients, and how the underlying IMID type influences treatment safety is unknown.
METHODS: We systematically searched PubMed/MEDLINE and Embase for studies evaluating the safety of anti-IL12/23 and -IL23 agents, and JAKi in older patients with IMIDs, including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. Eligible studies included patients who initiated therapy at age ≥50 years and reported outcomes in comparison with (1) younger patients receiving the same therapy, (2) older patients receiving non-AT, or (3) older patients receiving a different AT. Data on infections, major adverse cardiovascular events (MACE), venous thromboembolism (VTE), malignancy, and mortality were extracted. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a DerSimonian-Laird random-effects model.
RESULTS: Seventy-nine studies were included. Compared to other AT, JAKi were associated with a higher risk of infections (OR 1.38; 95% CI, 1.22-1.55) and serious infections (1.27; 1.06-1.52). No increase in MACE, VTE, or malignancy risk was seen overall. Among adults > 60 years, there was an increased risk of VTE in rheumatologic cohorts (3.28; 1.16-9.27) that was absent in IBD (0.99; 0.58-1.70) (p for difference = 0.045). Compared with anti-TNF, Anti-IL-12/23 and -IL-23 agents had a lower risk of serious infections (0.76; 0.68-0.84).
CONCLUSION: In older patients with IMIDs, anti-IL-12/23 and -IL-23 agents had lower serious infection risk while JAKi had an increased risk. JAKi showed a possible disease-specific thromboembolic signal in rheumatologic but not IBD cohorts.
PMID:42966459 | DOI:10.1016/j.cgh.2026.10.017