S4994 JAK of All Trades: Upadacitinib-Induced Remission of Medically Refractory Lymphocytic Colitis

Introduction: Microscopic colitis (MC) is an idiopathic, inflammatory colitis that causes chronic watery diarrhea and adversely impacts quality of life. Remission is defined clinically with the Hjortswang criteria (mean of <3 stools/day and <1 watery stool/day). Most patients respond to budesonide therapy, although relapse rates are high. Approximately 20% of patients have steroid-refractory disease. Guidelines recommend thiopurines, anti-tumor necrosis factor agents, and vedolizumab for budesonide-refractory MC. There is a paucity of data supporting these off-label advanced therapies, particularly for newer agents, such as the Janus-Kinase (JAK) inhibitors. Here, we present a case of upadacitinib-induced clinical remission of steroid-refractory lymphocytic colitis (LC) in a patient with concurrent celiac disease. Case Description/Methods: A 38-year-old woman with well-controlled celiac disease and LC previously responsive to budesonide presented with recurrent loose stools (4 stools/day), urgency, and incontinence. Colonoscopy confirmed active LC. The patient was not taking medications associated with MC risk. Stool pathogens were excluded, and tissue transglutaminase IgA suggested good celiac disease control. An 8-week course of ileal-release budesonide 9 mg daily did not induce remission. Off-label vedolizumab and adalimumab failed to induce symptomatic remission, and repeat histologic evaluations confirmed persistent LC activity. She began upadacitinib 45 mg daily induction dosing. Within 1 week, she achieved clinical remission with 1-2 Bristol Type 4 stools daily and no urgency or incontinence. After an 8-week induction, she transitioned to upadacitinib 30 mg daily maintenance dosing. Symptomatic remission has been sustained for over 11 months with no serious adverse effects. Discussion: Budesonide-refractory MC has a significant adverse impact on quality of life and no FDA-approved therapies. Case series show the potential efficacy of off-label advanced inflammatory bowel disease therapies (primarily anti-tumor necrosis factor and vedolizumab) in this setting. We’ve identified published cases of JAK inhibitor therapy for refractory MC, describing upadacitinib in 6 cases and tofacitinib in 1 case. In all cases, including ours, clinical remission was achieved rapidly (within days). Our patient’s rapid and sustained improvement with upadacitinib adds to the emerging evidence supporting the potential role for JAK inhibition as a refractory MC therapy. Future exploration in controlled studies is warranted.