Tofacitinib in Acute Severe Ulcerative Colitis—A Real-World Tertiary Center Experience

To the Editors, Tofacitinib, a Janus kinase inhibitor, has proven efficacy in the treatment of moderate to severe ulcerative colitis (UC).1 However, real-world data are limited and outcomes for tofacitinib in hospitalized patients with severe UC are scarce.2,3 Of patients presenting with acute severe UC (ASUC), 20% require colectomy and medical options in cases of prior anti-tumor necrosis factor (anti-TNF) failure or intolerance are extremely limited.4 We conducted a retrospective analysis of consecutive patients treated with tofacitinib in the inpatient setting at a tertiary inflammatory bowel disease referral center between February 2019 and February 2020. The primary outcome was need for colectomy during admission or follow-up. Table 1 summarizes the baseline characteristics and treatment outcomes of 7 anti-TNF refractory patients receiving in-hospital tofacitinib following intravenous hydrocortisone. The median disease duration was 51 months, and all patients with at least left-sided involvement had severe colitis at admission with a baseline Mayo endoscopic subscore of 3. Five patients met Truelove and Witts’s criteria for ASUC.5 Summary of Disease Characteristics and Treatment Outcomes of Hospitalized Patients Treated With Tofacitinib ADA indicates adalimumab; Alb, albumin (normal 40-52 g/L); AZA, azathioprine; CRP, C-reactive protein (normal 0-5 mg/L); CSF, corticosteroid-free; FCAL, fecal calprotectin; GOL, golimumab; Hb, hemoglobin (normal 130-170 g/L); IFX, infliximab; MES, Mayo Endoscopic Subscore; PRED, prednisolone; SF, stool frequency; UCEIS, ulcerative colitis endoscopic index of severity; UST, ustekinumab; VED, vedolizumab. Summary of Disease Characteristics and Treatment Outcomes of Hospitalized Patients Treated With Tofacitinib ADA indicates adalimumab; Alb, albumin (normal 40-52 g/L); AZA, azathioprine; CRP, C-reactive protein (normal 0-5 mg/L); CSF, corticosteroid-free; FCAL, fecal calprotectin; GOL, golimumab; Hb, hemoglobin (normal 130-170 g/L); IFX, infliximab; MES, Mayo Endoscopic Subscore; PRED, prednisolone; SF, stool frequency; UCEIS, ulcerative colitis endoscopic index of severity; UST, ustekinumab; VED, vedolizumab. Five of the 7 admitted patients (3 with ASUC) had a rapid clinical response with significant reduction of bloody stool frequency alongside normalization of C-reactive protein (<5 mg/L), facilitating hospital discharge between 2 and 7 days after first dose (median C-reactive protein in responders at admission = 13 mg/L). Of the patients discharged, 3 patients (2 with ASUC) showed marked endoscopic improvement postinduction (Fig. 1) and remain corticosteroid-free on maintenance tofacitinib. Endoscopic appearances for patients 2, 4, and 6 pre- and post-tofacitinib induction. Baseline endoscopy was undertaken during hospital admission and postinduction endoscopy at week 14 in all 3 cases. Patient 1 had superficial ulceration and spontaneous bleeding to 30 cm from the anal verge and had mucosal healing postinduction. Week 52 endoscopy (not shown) showed endoscopic and histological remission. Patient 4 had deep ulceration with significant mucosal congestion, edema, and luminal narrowing to the point of insertion (midsigmoid colon). The postinduction image shows marked improvement with healing. At endoscopy there was only a small area (<1 cm) of superficial ulceration in the sigmoid colon (not seen in photo). Patient 6’s baseline image shows loss of vascularity and superficial ulceration, and postinduction image shows mucosal healing. All patients remain steroid-free on maintenance tofacitinib with no readmission. Despite standard tofacitinib induction dosing throughout, 4 patients required subtotal colectomy, 2 during index admission (1 had cytomegalovirus-related colitis) and 2 following readmission within 90 days. Only 1 patient received tofacitinib directly after the failure of IV steroids and rescue infliximab on the same admission, without adverse events. No other drug-related adverse events were recorded. This study is the largest reported case series of the effectiveness of tofacitinib in hospitalized patients with severe colitis. Tofacitinib may have a role as a potential rescue agent in severe UC, with our experience showing the avoidance of surgery in 3 out of 7 steroid refractory hospitalized patients who had previously failed anti-TNF treatment. Its short half-life compared to other immunosuppressive therapies is advantageous in the event of treatment failure and need for surgery, potentially reducing the risk of postoperative complications. However, the failure rate of tofacitinib rescue therapy remains high, with the remaining 4 patients in our cohort eventually requiring colectomy. Further controlled studies are warranted evaluating the efficacy and safety of tofacitinib in this setting. Supported by: None. Conflicts of interest: SH has received lecture fees from Pfizer, Janssen, and Takeda and meeting support fees from Pfizer, Janssen, Vifor Pharma, Dr Falk Pharma, and Ferring. SR has received speaker fees from AbbVie and Takeda and meeting support fees from Pharmacosmos. MAS has served as a speaker, a consultant, and/or an advisory board member for Sandoz, Janssen, Takeda, MSD, Dr Falk Pharma, and Samsung Bioepis. PMI has received lecture fees from AbbVie, Warner Chilcott, Ferring, Dr Falk Pharma, Takeda, MSD, Johnson & Johnson, Shire, and Pfizer. Advisory fees were received from AbbVie, Warner Chilcott, Takeda, MSD, Vifor Pharma, Pharmacosmos, Topivert, Genentech, Hospira, and Samsung Bioepis.