Tofacitinib for Acute Severe Ulcerative Colitis: A Systematic Review

Abstract

Background Tofacitinib has emerged as a new potential treatment for acute severe ulcerative colitis (ASUC). We conducted a systematic review to assess efficacy, safety, and integration in ASUC algorithms. Methods Systematic search in MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov until August 17, 2022, including all studies reporting original observations on tofacitinib for ASUC, preferably defined according to Truelove and Witts criteria. Primary outcome was colectomy-free survival. Results Of 1,072 publications identified, 21 studies were included of which three were ongoing clinical trials. The remaining comprised a pooled cohort originating from 15 case publications (n=42), a GETAID cohort study (n=55), a case-control study (n=40 cases), and a pediatric cohort (n=11). Of these 148 reported cases, tofacitinib was used as second line treatment after steroid failure in previous infliximab failures or third line after sequential steroid and infliximab or cyclosporine failure, 69 (47%) were female, age median ranged 17-34 years, disease duration 0.7-10 years. Overall, 30-day colectomy-free survival was 85% (n=123 of 145; n=3 without colectomy had follow-up <30 days), 90-day 86% (n=113 of 132; n=16 follow-up <90 days), and 180-day 69% (n=77 of 112; n=36 follow-up <180 days). Tofacitinib persistence at follow-up was 68-91%, clinical remission 35-69%, and endoscopic remission 55% reported. Adverse events occurred in 22 patients, predominantly being infectious complications other than herpes zoster (n=13), and resulted in tofacitinib discontinuation in seven patients. Conclusion Tofacitinib appears promising for treatment of ASUC with high short-term colectomy-free survival among refractory patients otherwise deemed for colectomy. However, large high-quality studies are needed.

Effectiveness and safety of a third‐line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study)

“…This rate is roughly similar to previous studies on ASUC setting for sequential treatment with IFX‐CyA and vice versa 45 . Although there are limited data for tofacitinib in ASUC in the long term, clinical remission rates of 34% at week 14 have been described, which are slightly lower than our results 41,46,47 . Of note, a recent American study revealed that tofacitinib 10 mg three times daily for the treatment of ASUC was protective against colectomy in bio‐experienced patients 39 …”

“…45 Although there are limited data for tofacitinib in ASUC in the long term, clinical remission rates of 34% at week 14 have been described, which are slightly lower than our results. 41,46,47 Of note, a recent American study revealed that tofac- On the other hand, the simultaneous use of corticosteroids, immunomodulators, biologics, and JAK inhibitors, increase the risk of complications and treatment combination or sequencing is frequently needed for ASUC. 51,52 Moreover, high risk of postoperative complications and infections has been observed when colectomy is delayed.…”

JAK inhibitors for the treatment of inflammatory bowel disease: results of an international survey of perceptions, attitudes, and clinical practice

“…The positive results from the upadacitinib phase III programme in early 2022 may have encouraged pre-licensing use in CD if local policies allowed this. Off-label JAKi use for the treatment of ASUC is unsurprising given the potency and rapidity of onset of JAKi together with the accumulating evidence for their use in this setting [21,22]. Outcomes from the clinical trials of tofacitinib in ASUC are eagerly awaited [23,24].…”

Ulcerative Colitis in Adults

“…Infliximab is the most commonly used rescue agent because cyclosporine is solely an induction agent. In patients with ASUC hospitalized following anti-TNF therapy, observational data demonstrated that tofacitinib may be used as salvage therapy to avoid colectomy (90-day colectomy-free survival of 86%) . Tofacitinib, 10 mg, 3 times daily for 3 days followed by 10 mg twice daily had lower rates of colectomy at 90 days (tofacitinib, 8.3% vs control, 20.4%; hazard ratio, 0.11 [95% CI, 0.02-0.56]); however, randomized trials are required to establish the role of JAK inhibitors in the treatment of ASUC …”