COMBINATION BIOLOGIC AND SMALL MOLECULE THERAPY FOR REFRACTORY ULCERATIVE COLITIS

Abstract INTRODUCTION Some inflammatory bowel disease (IBD) patients do not achieve remission with maximal medical therapy. We present a case of refractory UC who achieved clinical, endoscopic, and histologic remission after combining biologic and small molecule therapy. CASE DESCRIPTION A 25-year-old Caucasian male was referred to our clinic for refractory UC. Since diagnosis four years prior, he failed mesalamine, azathioprine (intolerant), adalimumab (secondary nonresponse), vedolizumab (secondary nonresponse) with inability to taper prednisone. Upon presentation to our clinic he was at week 14 of infliximab therapy without clinical improvement. Therapeutic drug monitoring revealed adequate infliximab levels without antibodies. Colonoscopy revealed mayo 2-3 disease with discrete ulcerations (Figure 1). Due to primary non-response, he was initiated on ustekinumab (UST). He remained clinically active despite dose escalation up to evey four weeks and prednisone use. Tofacitinib was initiated with initial clinical improvement, then worsening after 3 months. The Tofacitinib dosing was increased from twice daily to three times daily and repeat colonoscopy revealed pan-colitis with Mayo 2 disease. Due to refractory disease the patient was started on combined therapy of tofacitinib twice daily with UST. On dual therapy the patient experienced progressive clinical improvement. After a year of dual treatment colonoscopy showed no disease activity, and biopsies showed no evidence of cryptitis, or crypt abscesses or active inflammatory infiltrate (Figure 2). DISCUSSION This case highlights the benefit of combination biologic therapy with small molecule therapy in medically refractory IBD. There are limited prospective data to endorse the widespread implementation of combination therapy. A meta-analysis of thirty studies, involving 279 patients, reported 59% were able to achieve clinical remission and 34% achieved endoscopic remission with treatment of dual biologic or small molecule therapy1. Concerns involving safety of combination biologic and small molecule therapy continue to be evaluated. In our case, the patient achieved clinical, endoscopic, and histologic remission with tofacitinib and UST without adverse effects. We present this case to support the safety and efficacy of combination therapy in medically refractory patients. REFERENCES Ahmed W, Galati J, Kumar A et al. Dual Biologic or Small Molecule Therapy for Treatment of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2021. https://doi.org/10.1016/j.cgh.2021.03.034.