JAK Inhibitors in ASUC: A Systematic Review: AJG March 2026

Acute severe ulcerative colitis (ASUC) is a life-threatening complication of ulcerative colitis that often requires hospitalisation and urgent therapy. Although intravenous corticosteroids remain the standard first-line treatment, a significant proportion of patients fail to respond and require rescue therapy or colectomy. Janus kinase (JAK) inhibitors, such as tofacitinib and upadacitinib, have emerged as rapidly acting oral immunomodulators and are increasingly being explored as therapeutic options in ASUC.

This systematic review and meta-analysis evaluated the effectiveness and safety of JAK inhibitors in ASUC by analysing 35 studies including 664 patients. In the short term (<1 month), clinical response rates were high, reaching 77.9% with tofacitinib and 86.5% with upadacitinib, with colectomy rates around 11% for both drugs. At intermediate follow-up (<3 months), pooled clinical response and remission rates remained moderate, with remission observed in 37.3% (tofacitinib) and 47.4% (upadacitinib) of patients. In the long term (3–12 months), sustained clinical response and remission rates ranged from 33%–41%, while colectomy rates were approximately 22%–23%.

Safety outcomes were acceptable. Adverse events included venous thromboembolism (2.2%), herpes zoster infection (3.4%), and major adverse cardiovascular events (0.7%), all occurring at relatively low frequencies. Importantly, high-dose tofacitinib did not demonstrate superior efficacy compared with standard dosing.

Overall, the analysis suggests that JAK inhibitors are effective and reasonably safe as adjunct therapy with corticosteroids or as rescue therapy in steroid-refractory ASUC. However, the authors emphasize that well-designed randomized controlled trials are still required to clearly define their optimal role in ASUC management.