P044 EFFICACY OF INDUCTION THERAPY WITH HIGH-INTENSITY TOFACITINIB IN 4 PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS. (7th February 2019)

• Record Type: Journal Article
• Authors: Berinstein, Jeffrey; Steiner, Calen; Regal, Randolph; Allen, John; Kinnucan, Jami; Stidham, Ryan W; Waljee, Akbar K; Bishu, Shrinivas; Aldrich, Leslie; Higgins, Peter
• Is Part Of: Inflammatory bowel diseases. Volume 25(2019)Supplement 1
• Page Start: S22
• Page End: S23
• Publication Date: 2019-02-07
• Subjects: Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1093/ibd/izy393.050
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract: Background: Acute severe ulcerative colitis (ASUC) is a serious presentation of ulcerative colitis (UC) that carries a high risk for medical failure. First line therapy relies on IV corticosteroids, however up to 30% of patients will not respond. Even when second line rescue therapy with infliximab or cyclosporine is used, there is still significant rates of medical failure leading 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. We present the first reported use of off-label, high-intensity, tofacitinib, in four patients admitted with ACUS predicted to fail medical management. Methods: All four patients with ASUC had a high likelihood of failing medical therpay based on severe Truelove and Witt's criteria, C-reactive protein (CRP) >100 mg/L at presentation, endoscopic features during admission, and prior failure of IV corticosteroids or infliximab therapy (Table 1). Clostridium difficile and cytomegalovirus colitis were. These patients were offered total abdominal colectomy or tofacitinib at 10mg three times daily for 9 doses. Three of the four patients received IV methylprednisolone 60mg daily in addition to tofacitinib. One patient received tofacitinib in addition to budesonide due to a previous corticosteroid-induced exacerbation of psychiatric illness. IRB approval was obtained for this retrospective case series. Results: After receiving tofacitinib, all four patients had a rapid improvement in patient-reported clinical symptoms and decline in CRP (Figure 1). Patient 1 and patient 2 achieved clinical remission with IV corticosteroids and tofacitinib, while patient 4 achieved clinical remission with tofacitinib and budesonide. Only patient 3, who had the most elevated CRP (242 mg/L) and severe colonic dilation despite receiving more than 7 days of IV corticosteroids at an outside hospital, was unable to achieve clinical remission. Patient 4, with the contraindication to systemic corticosteroids, provides proof of concept that tofacitinib therapy may be an effective induction agent in the treatment of ASUC even without systemic corticosteroids. No major adverse effects were reported during the induction phase of drug administration or up to 18 months of reported follow-up. Discussion: The rapid improvement in clinical symptoms and inflammatory biomarkers after 10 mg t.i.d. of tofacitinib therapy, including patient 4 who did not receive IV corticosteroids, provides convincing support that tofacitinib could be an effective therapeutic augmentation option for patients with ASUC likely to fail first-line medical management. Additional trials are needed to identify the optimal dose, frequency, duration, and safety of high-intensity tofacitinib in patients presenting with ASUC. Figure 1. CRP improvement after initiation of tofacitinib. + Indicates when tofacitinib was initiated. *Indicates when the dose of tofacitinib was reduced.