S2283 Use of Ruxolitinib for the Simultaneous Treatment of Ulcerative Colitis and Polycythemia Vera

Abstract

INTRODUCTION: Janus Associated Kinase (JAK) inhibitors are a relatively new class of small molecule kinase antagonists. Tofacitinib, a JAK1/3 inhibitor, is currently the only medication in this class approved for treatment of moderate to severe ulcerative colitis (UC). Ruxolitinib, a selective JAK1/2 inhibitor, is approved to treat polycythemia vera (PV), myelofibrosis, and acute graft-vs-host disease. This case describes the use of ruxolitinib for successful treatment of a patient with both UC and PV. CASE DESCRIPTION/METHODS: A 61-year-old man was originally diagnosed with pan-UC at age 35. His medical history included JAK2 V617F mutated PV diagnosed at age 49, managed with hydroxyurea. His UC was initially treated with mesalamine for 15 + years despite persistent symptoms, given he failed azathioprine due to nausea and vomiting. When he first presented to our clinic with diarrhea and hematochezia, endoscopy revealed severe active pancolitis. Therapy was escalated to infliximab + methotrexate but methotrexate was stopped due to neutropenia. At six months follow up, endoscopic evaluation showed persistent active colitis and labs showed undetectable drug level, high antidrug antibodies, and elevated fecal calprotectin. He was switched to vedolizumab. Symptoms persisted at six months follow up; therefore, infusion frequency was increased to every four weeks from every eight. Months later, symptoms were unchanged, and endoscopy showed moderately severe colitis. During this time, his PV worsened with cardiovascular complications including myocardial infarction and claudication. In discussion with his hematologist, he was switched from hydroxyurea to ruxolitinib to treat his PV, while also discontinuing vedolizumab, hoping this would improve his UC without additional immunosuppression. At six months follow up his UC symptoms had significantly improved and his PV was at goal. At 18 months follow up his UC symptoms had resolved and endoscopy showed marked improvement with chronic quiescent disease on biopsy. DISCUSSION: The combination of UC and poorly controlled PV provided a unique opportunity to treat both conditions with a single drug, ruxolitinib, using a multidisciplinary approach. This case may support the need for further studies to investigate the effectiveness and safety of alternative JAK inhibitors other than tofacitinib, for UC.