Upadacitinib as a rescue therapy for steroid- and infliximab-refractory acute severe ulcerative colitis: short- and long-term effectiveness and safety in a multicenter cohort study: GI Signals

IBD prospective cohort · n=50 · Jul 22, 2026 · Inflamm Bowel Dis · IF 4.5

Upadacitinib as a rescue therapy for steroid- and infliximab-refractory acute severe ulcerative colitis: short- and long-term effectiveness and safety in a multicenter cohort study.

New evidenceulcerative colitisJAK inhibitors

Clinical takeawayIn hospitalized patients with ASUC refractory to IV corticosteroids and infliximab, use upadacitinib as a third-line rescue therapy. Early response is evident by week 1 (60% clinical remission); among patients continuing treatment, improvements in symptoms and CRP are maintained through week 48 (51% CR). However, 48% discontinued by week 48, primarily due to nonresponse (42%) or loss of response (46%). Colectomy occurred in 22% (elevated with higher baseline CRP). Monitor baseline CRP as a risk factor for colectomy.

What it foundIn ASUC patients who failed IV corticosteroids and infliximab, upadacitinib achieved clinical remission in 60% by week 1 and 51% by week 48, with colectomy in 22% and adverse events in 24% (nearly all nonsevere).

ContextDemonstrates upadacitinib induces rapid remission in steroid- and infliximab-refractory ASUC with acceptable safety (24% adverse events, nearly all nonsevere), supporting its use as a third-line rescue option when initial biologic therapies fail. Sustained response observed in patients who continue therapy.

Reinforcessuggested applicable standard· ACG Clinical Guideline Update: Ulcerative Colitis in Adults, Am J Gastroenterol 2025;120(6):1187-1224; AGA Living Guideline on Pharmacological Management of Moderate-to-Severe UC, Gastroenterology 2024 (panel review March 2026, no changes)

Decision at stakeUse JAK inhibitors as third-line rescue therapy for acute severe ulcerative colitis refractory to intravenous corticosteroids and anti-TNF agents

Confirm ulcerative colitis with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step CDI testing. … Screen for acute severe UC by Truelove-Witts and admit for IV steroids. …

From our summary of this standard, unedited — the part the paper bears on. … marks omitted text. Our wording, not the guideline's; read the source for its own text.

Our full summary of this standard

Confirm ulcerative colitis with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step CDI testing. Treat mild-moderate disease with 5-ASA by route and extent (suppository for proctitis, enema for left-sided, oral plus rectal for extensive); if 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by EFFICACY TIER, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab; intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab; lower: adalimumab. PREVIOUSLY TNF-EXPOSED, higher efficacy: tofacitinib, upadacitinib, ustekinumab; lower: adalimumab, vedolizumab, ozanimod, etrasimod - S1P modulators are weakest in exactly this group. Do not cycle within the anti-TNF class after primary non-response; switch mechanism. Apply treat-to-target (STRIDE-II) to endoscopic improvement (MES 0-1). Screen for acute severe UC by Truelove-Witts and admit for IV steroids. Begin CRC surveillance 8-10 years after DIAGNOSIS for extensive or left-sided disease; isolated proctitis follows average-risk screening.

ACG Clinical Guideline Update: Ulcerative Colitis in Adults, Am J Gastroenterol 2025;120(6):1187-1224; AGA Living Guideline on Pharmacological Management of Moderate-to-Severe UC, Gastroenterology 2024 (panel review March 2026, no changes) ↗

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