Tofacitinib in Acute Severe Ulcerative Colitis: Case Series and a Systematic Review

Dear Editors, The meta-analysis by Taxonera et al1 has shown the effectiveness of tofacitinib in refractory moderate to severe ulcerative colitis with an acceptable safety profile. There is increasing interest regarding the use of tofacitinib in acute severe ulcerative colitis (ASUC) because of its quick onset of action. We report our experience on the use of tofacitinib in ASUC and a systematic review of similar reports. Four patients hospitalized for ASUC were initiated on tofacitinib over 6 months. These patients had Mayo scores of at least 10 at admission. All 4 had failed to respond to intravenous steroids. In addition, 2 patients had also failed intravenous infliximab as second-line therapy and 1 had failed intravenous cyclosporine. Three patients had clinical improvement with reduction in stool frequency and resolution of blood in stools and were able to avoid colectomy. One patient had COVID-19 infection and improved initially, but had a sudden deterioration 4 weeks later with sudden-onset breathlessness and died. The other 2 patients are doing well at the time of this writing. One patient failed to respond to tofacitinib and underwent colectomy (Supplementary Table 1). We searched PubMed and Embase on February 24, 2021, using the keywords “acute severe ulcerative colitis” and “Tofacitinib” (detailed search strategy in Supplementary Table 2). The process of study screening and selection is shown in Fig. 1. Eventually, 6 studies (4 case series including the present series and 2 case reports) were included in the systematic review. Our analysis of 21 patients with ASUC showed an efficacy of 75% (3/4) as first-line therapy, 85.7% (12/14) as second-line therapy (steroid failure), and 66.6% (2/3) as third-line therapy. The initial doses used were variable (20-30 mg/day; Table 1). The adverse events reported were truncal maculopapular rash, fatigue and body ache, and possible pulmonary thromboembolism in 1 patient. Details of the Included Studies of Tofacitinib as Rescue Therapy in Acute Severe Ulcerative Colitis ADA indicates adalimumab; ASA, aminosalicylates; AZA, azathioprine; BD, twice a day; f/b, followed by; GOL, golimumab; IFX, infliximab; MPS, methylprednisolone; PTE, pulmonary thromboembolism; TDS, thrice a day; USK, ustekinumab; VED, vedolizumab. Details of the Included Studies of Tofacitinib as Rescue Therapy in Acute Severe Ulcerative Colitis ADA indicates adalimumab; ASA, aminosalicylates; AZA, azathioprine; BD, twice a day; f/b, followed by; GOL, golimumab; IFX, infliximab; MPS, methylprednisolone; PTE, pulmonary thromboembolism; TDS, thrice a day; USK, ustekinumab; VED, vedolizumab. PRISMA flow chart detailing the process of study selection. Although the available data were derived from a small number of patients, tofacitinib seems to be an effective rescue therapy in ASUC, reducing the need for colectomy. However, there could be concerns regarding a heightened risk of thrombosis in the setting of ASUC. In 1 patient (who also had associated recent COVID-19 infection and hypoalbuminemia), sudden-onset breathlessness and hypoxemia suggested pulmonary thromboembolism. Large randomized prospective trials should examine the efficacy of tofacitinib in comparison to infliximab and cyclosporine as a possible therapy for medical rescue in steroid-refractory ASUC.