Tofacitinib May Effectively Treat Refractory Acute, Severe Ulcerative Colitis

Tofacitinib should be considered a new treatment option for acute, severe ulcerative colitis.

Tofacitinib reduced the need for colectomy in around 85% of refractory patients with acute, severe ulcerative colitis (ASUC) deemed for colectomy, suggesting it may offer a promising alternative treatment, according to study findings published in the Journal of Crohn’s & Colitis.

Tofacitinib is a small molecule monotherapy, targeting the Janus kinase (JAK) signaling pathway. It is used as an alternative therapy to treat UC following inadequate response or patient intolerance to other biologic therapies.

Researchers conducted a systematic review of the literature archived on MEDLINE, EMBASE, Cochrane Library, and until August 17, 2022. They summarized and analyzed available data on the efficacy, safety, and integration of tofacitinib as a treatment for ASUC.

They identified 1,072 publications, including 21 in their review, 3 of which were ongoing clinical trials. The remaining 18 studies comprised 148 patients (women, 47%) with ASUC with a median age range between 17 and 34 years.

[T]ofacitinib appears promising for treatment of ASUC with notable 30-day and 90-day colectomy-free survival of 85%…

These 148 patients with ASUC received treatment with tofacitinib either as a second- or third-line treatment after failure of steroids plus infliximab or steroids plus infliximab followed by failure of cyclosporine.

Efficacy of tofacitinib was based on colectomy-free survival within 30 days, 90 days, and 180 days following treatment. Secondary outcomes included clinical and endoscopic remission according to the full Mayo score, partial Mayo score, and Mayo endoscopic subscore. Safety was assessed according to reported adverse events.

Overall, 85% of patients achieved a global 30-day colectomy-free survival. The remaining 3 patients were assessed prior to the 30-day cutoff; however, they also remained colectomy-free. After 90 days, 86% of patients achieved colectomy-free survival with 16 colectomy-free patients seen prior to the 90-day cutoff. After 180 days, 69% of patients remained colectomy-free with 36 colectomy-free patients seen prior to the 180-day cutoff.

Between 35% and 69% of patients taking tofacitinib achieved clinical remission and approximately 55% reported endoscopic remission. Maintenance doses ranged between 5 and 10 mg twice daily; however, tapering regimens and use of steroids were not consistently reported across all studies. At follow-up, persistent tofacitinib use remained high, ranging between 68% and 91% of patients.

Adverse events mainly included infectious complications other than herpes zoster. Seven of the 22 patients who experienced adverse events discontinued treatment with tofacitinib.

Tofacitinib appears promising for treatment of ASUC with notable 30-day and 90-day colectomy-free survival of 85% and thus seemingly comparable to iv corticosteroids even among refractory patients deemed for colectomy,” the study authors wrote. “Our findings should, however, be interpreted with great caution because of limited observations and low quality of currently available studies with high risk of bias and confounding.”

Study limitations include lack of standardized reporting on clinical, endoscopic, and safety outcomes, potential lack of representation across all patients with acute severe UC, the fact that not all patients included in the studies met the formal criteria for acute severe UC, and inconsistent and low-quality, uncontrolled data introducing a high risk of bias and confounding.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for full list of authors’ disclosures.


Steenholdt C, Ovesen PD, Brynskov J, Seidelin JB. Tofacitinib for acute severe ulcerative colitis: a systematic review. J Crohns Colitis. Published online March 11, 2023. doi:10.1093/ecco-jcc/jjad036