Efficacy of Induction Therapy With High-Intensity Tofacitinib in 4 Patients With Acute Severe Ulcerative Colitis

Abstract

As many as 25% of patients diagnosed with ulcerative colitis are hospitalized with an episode of acute severe ulcerative colitis (ASUC). 1 The standard of care for patients hospitalized with ASUC relies on rapid induction with intravenous (IV) corticosteroids. Up to 30% of patients do not respond to corticosteroids alone. 2 Rescue therapy with infliximab or cyclosporine has been shown to reduce rates of colectomy to 20% by 90 days. 3,4 This still represents a significant rate of treatment failure, which leads to an unplanned and irreversible surgery. In recent years, increasing numbers of patients admitted with ASUC have already failed infliximab therapy, highlighting the need for additional treatment options for these patients. Tofacitinib is a rapidly acting, oral, small-molecule Janus kinase inhibitor that was recently approved by the Food and Drug Administration for treatment of ulcerative colitis. 5 We present the first reported use of off-label, high-intensity tofacitinib in 4 patients admitted to our institution with ASUC predicted to fail medical management. MethodsAll 4 patients with ASUC had a high likelihood of failing IV corticosteroid monotherapy based on severe Truelove and Witt's criteria, C-reactive protein (CRP) >100 mg/L at presentation, endoscopic features during admission (Figure 1A-1D

Long-term outcomes of infliximab in a real-world multicenter cohort of patients with acute severe ulcerative colitis

“…Further clinical trials with different biologics or small molecules are also needed in this setting. 32,33 In conclusion, we have reported the favorable short-term and long-term outcomes of IFX treatment in Korean patients with ASUC, pointing to IFX as an effective therapeutic option in such a critical situation. We believe that IFX can be considered as a first-line option for the treatment of ASUC, in highly selected patients, who cannot receive initial therapy with IVCS.…”

Ulcerative Colitis: Current and Emerging Treatment Strategies

“…The use of tofacitinib has been investigated in ASUC, given its rapid onset of action, its appropriateness and efficacy as both an induction and maintenance agent, and, relatedly, its safety profile. In a small retrospective series of four hospitalized patients with ASUC, high intensity tofacitinib dosed as 10 mg three times a day was associated with rapid improvement in clinical symptoms and inflammatory biomarkers [68]. These results suggest tofacitinib could be an effective therapeutic option for patients with ASUC who previously failed TNF inhibitors.…”

Treatment Algorithm for Mild and Moderate-to-Severe Ulcerative Colitis: An Update

“…If patients are not responding to IV corticosteroids within 3-5 days, having sustained fever, bloody diarrhea ≥4 times daily, or elevated CRP, rescue therapy with ciclosporin or infliximab must be considered [85,86]. Only case reports exist for the use of tofacitinib in this clinical scenario [87]. Extending IV corticosteroid ther- apy beyond 7-10 days has no benefit [84].…”