Abstract Background Colectomy rates in acute severe UC (ASUC) have stabilized around 10-15% in the biologic era. One strategy aiming at further lowering colectomy rates following failure of steroids and a first-line rescue therapy with infliximab or Cyclosporin (CsA), is to utilize a sequential 2nd-line rescue therapy with either medication. This approach has shown promising results, salvaging up to 60% of colons at 12 months. Nonetheless, the potential for serious adverse events and fear of missing the window of opportunity for colectomy limited the wide implementation of this strategy. With growing evidence supporting their use as 1st-line rescue therapy, the role of Janus kinase inhibitors (JAKi) as 2nd-line rescue therapy in ASUC requires further evaluation. Methods A Systematic literature search was conducted through December 2024, including studies reporting original observations on adult patients with ASUC who had failed steroids and a 1st-line rescue with either IFX or CsA, and were subsequently treated with a JAKi during the same ASUC presentation. Eligible patients received their JAKi within Less than 8 weeks following failure of the 1st rescue therapy. Reports of single cases were excluded. Outcomes of interest were clinical response, remission, and colectomy-free survival. Data were retrieved from individual patients, then pooled and analysed collectively as a single cohort. Results Eleven studies reported on tofacitinib (tofa) and seven on upadacitinib (upa), enrolling a total of 90 patients (60 tofa, 30 upa). All studies were observational. ASUC was primarily defined according to Truelove and Witt’s criteria. 30% of patients were bio-experienced. The length of follow-up varied across studies, ranging from 1 to 12 months, with 15 and 11 of 18 studies reporting 3- and 6-month follow-up, respectively. Response rates during the index admission were 77% for the combined JAKi group, with equal rates in the tofa and upa groups. Remission rates at last follow-up were 41% for JAKi, 42% for tofa, and 38% for upa. Colectomy rates at 1, 3, and 6 months were 22%, 23%, and 28% for JAKi, with comparable rates between tofa and upa. (figs 1 9(3):251-262. doi:10.1016/S2468-1253(23)00313-8 2. Inflamm Bowel Dis. 2015;21(7):1683-1694. doi:10.1097/MIB.0000000000000350 3. J Crohns Colitis. 2025;19(2):jjaf021. doi:10.1093/ecco-jcc/jjaf021. Conflict of interest: Dr. Daher, Saleh: No conflict of interest Kalisky, Itay: Non Shafrir, Asher: No conflict of interest Rosenfeld, Greg: Grant: Research Grants provided by Abbvie, Pfizer, Ferring, Infoway Canada and Crohn’s and Colitis Canada Educational Grants from Celltrion, and Fresenius-Kabi Personal Fees: Speaker and Consultant fees provided by Abbvie, Celltrion, Ferring, Fresnius-Kabi, Takeda, Merck, Pfizer, Amgen, Viatris, Orgenon Bressler, Brian: No conflict of interest
Daher et al. (Thu,) studied this question.