Rowan BANDARANAIKE, Benjamin HEWITT, Samuel TARWATER
Euroasian Journal of Hepato-Gastroenterology - 2026;16(1):56-63
Aims and background: Janus kinase (JAK) inhibitors have reshaped the pharmacotherapeutic armamentarium for inflammatory bowel disease (IBD), distinguished by oral dosing, ambient-temperature stability, immunity from anti-drug antibody formation, and a characteristically brisk pharmacodynamic onset, properties that collectively set them apart from injectable biologic agents. The epidemiological footprint of IBD is expanding at an accelerating pace across Eastern Europe, Central Asia, and the Middle East, yet meaningful access to biologic therapies remains starkly uneven, constrained by coldchain dependencies, infusion-facility prerequisites, immunogenicity monitoring demands, and financial barriers. Prior reviews have been anchored to Western regulatory paradigms without examining the qualitatively distinct therapeutic roles JAK inhibitors could assume in resource-variable healthcare environments. This narrative review synthesizes comparative efficacy, tolerability, and logistical evidence for JAK inhibitors vs biologic agents and proposes a regionally grounded framework for their integration into the Euroasian IBD treatment pathway. Methods: A structured literature search of PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials was performed through March 2026, targeting randomized controlled trials (RCTs), network meta-analyses (NMAs), comparative effectiveness investigations, real-world cohort analyses, and contemporary clinical practice guidelines [American College of Gastroenterology (ACG) 2025, American Gastroenterological Association (AGA) 2024-2025, and European Crohn's and Colitis Organization (ECCO) 2025] addressing JAK inhibitors and biologic agents in moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). Endpoints of interest spanned clinical remission, endoscopic improvement, histologic remission, rapidity of symptomatic relief, and safety parameters encompassing herpes zoster reactivation, major adverse cardiovascular events (MACE), and venous thromboembolism (VTE). Results: Multiple NMAs position upadacitinib at the apex for clinical remission induction in UC (p-score 0.98-0.99), with sustained superiority across both biologic-naïve and biologic-experienced subpopulations. Pivotal phase III data in CD demonstrated clinical remission in 38.9-49.5% of upadacitinib-treated patients vs 21.1-29.1% receiving placebo (p < 0.001). With respect to onset kinetics, JAK inhibitors outpace every biologic class; upadacitinib produced symptomatic remission in 68% by week 2, contrasted with 15.7-22% for vedolizumab, ustekinumab, and tumor necrosis factor (TNF) antagonists. Among heavily pretreated real-world patients (median four prior advanced therapies), 64% achieved clinical remission by week 12, and dose re-escalation recaptured therapeutic response in 60%. Herpes zoster incidence is appreciably elevated [number needed to harm (NNH) 83-97], reinforcing the imperative for pre-treatment immunization. Cardiovascular and thromboembolic signals from the ORAL surveillance rheumatoid arthritis trial have not been substantiated in IBD-specific populations [hazard ratio (HR) 0.50-1.08 for MACE; HR 0.66-1.06 for VTE vs anti-TNF therapy]. Conclusion: Within resource-variable Euroasian healthcare systems, JAK inhibitors may merit a substantially earlier position in the IBD treatment sequence than Western algorithms currently prescribe, by virtue of logistical attributes that circumvent the infrastructure constraints impeding biologic utilization. This review presents the first regionally anchored framework for deploying JAK inhibitors in clinical contexts where the operative decision is not between a JAK inhibitor and a biologic, but between a JAK inhibitor and the total absence of advanced therapy.
