HIGH DOSE TOFACITINIB AS SALVAGE THERAPY IN STEROID REFRACTORY ACUTE SEVERE ULCERATIVE COLITIS FOLLOWING NON-RESPONSE TO INFLIXIMAB

Abstract

Abstract INTRODUCTION Acute Severe Ulcerative Colitis (ASUC) requiring hospitalization remains a serious concern in patients with Ulcerative colitis. In patients with steroid-refractory disease, Intravenous infliximab salvage therapy is used. Colectomy is reserved for patients refractory, even to salvage therapy. We present a young female with ASUC, who was successfully treated with high dose Tofacitinib after Steroids and Infliximab failure. CASE HISTORY A 23 years old female was diagnosed with pan-UC six months prior to the first presentation at our center. Since then, she has had a Steroid dependent disease. She was on the maximum 5-Aminosalicylic dose and could not tolerate azathioprine in the past. At the presentation, she had iron deficiency anemia (10.1 gm/dL), hypoalbuminemia (27 gm/L), C-reactive protein 4 mg/L and calprotectin of 670 mg/Kg. The colonoscopy showed pan-colitis Mayo score 3. Given her steroid dependency for the last six months, she was started on Infliximab induction followed by maintenance. After the second Induction dose of Infliximab, the patient was admitted with worsening of her clinical symptoms. Sigmoidoscopy was performed for the patient, which showed severe colitis. Biopsy showed cytomegalovirus inclusion by immunohistochemistry. The third dose of Infliximab was postponed, and the patient received IV ganciclovir followed by oral therapy for two weeks duration. She responded clinically but before her third dose again had worsening of the disease. At the time of admission, she had a hemoglobin of 7.1 gm/dL, albumin 21 gm/L, CRP 72 mg/L, and calprotectin of 1352 mg/Kg. She met Truelove and Witts criteria for ASUC with a Mayo score of 12. Sigmoidoscopy again showed pan-colitis but was negative for cytomegalovirus. The patient did not respond to 60 mg methylprednisolone daily for five days. She was re-inducted with High dose infliximab and was given two doses 10 mg/Kg one week apart. However, the Mayo score showed no improvement, and surgery was consulted for possible colectomy. After discussing with the patient, we started her on a high dose Tofacitinib of 10 mg three times a day as salvage therapy. She showed dramatic improvement within the next 72 hours, and by day five, was discharged home. Her hemoglobin improved, CRP normalized. At three months, calprotectin was less than 100 mg/Kg, and colonoscopy showed mucosal healing with a Mayo score of 1. DISCUSSION In Steroid refractory ASUC, with non-response to Infliximab, High-dose tofacitinib can be used as rescue therapy. Our patient showed clinical and biochemical remission within three days. At three months follow up, the patient remained colectomy-free and was in sustained remission.