UPADACITINIB RESOLVES DIARRHEA AND FECAL CALPROTECTIN ABNORMALITIES IN BUDESONIDE-DEPENDENT MICROSCOPIC COLITIS
Authors: Hassan Syed Adeel , Kasem Ahmad , Elsayed Mohamed , Perry Courtney , Flomenhoft Deborah , Barrett Terrence 
Published: January 2024

Abstract

BACKGROUND
Current American Gastroenterological Association guidelines are devoid of recommendations for steroid and biologic refractory microscopic colitis (MC). Upadacitinib (UPA) is a small molecule that selectively inhibits janus kinase-1 (JAK1). Evidence pertaining to its utility in the management of steroid and biologic refractory MC remains limited. Herein, we report efficacy and safety of UPA in medically refractory MC.

METHODS
Three patients presenting with severe MC refractory to budesonide and biologic therapy (vedolizumab, Table 1) were treated with standard UPA therapy. UPA was initiated at standard induction of 45 mg/day for 8 weeks. All patients had their UPA reduced to 30 mg/d for maintenance. Therapeutic response was assessed using Hjortswang’s criteria (HC), and serial fecal calprotectin measurements. HC defines clinical remission as &lt; 3 bowel movements (BM)/day and &lt; 1 watery stools/day. Active disease was defined as ≥ 3 BM/day or ≥1 watery stool/day. FC &lt; 150 ug/g was deemed normal.

RESULTS
Three patients (Table 1) were included in this study. Overall, our cohort had 2 cases of collagenous colitis and 1 case of lymphocytic colitis. Two patients had an association with diagnosis of celiac disease. All patients failed steroid and biologic therapy (Table 1) with an average of 5 failed medications. At the end of UPA induction, all patients attained &lt; 3 BM/day (% reduction: -79%±6). Resolution of abdominal pain, nocturnal stooling, fatigue and fecal urgency were observed. As per HC, 1 patient displayed clinical remission and two achieved significant symptomatic improvement (Table 2). All patients displayed significant reductions in FC (-71%±1.5). At 16 weeks, none of the patients experienced LBM (-100%±0) and all resolved abdominal pain, nocturnal stooling, fatigue and fecal urgency (Table 2). FC normalized (-93%±6.4) in all three patients (Table 3). No serious infections, cardiovascular events or thromboembolic events occurred. One patient experienced gout and required further UPA dose reduction to 15 mg/day. This patient continues to maintain remission at 15 mg/day.

DISCUSSION
UPA is a novel JAK1 inhibitor with a favorable pharmacokinetic profile. It’s rapid onset of action and relative safe profile compared to chronic steroid use makes it an ideal treatment for refractory MC. The pathophysiology of MC remains poorly elucidated. It is postulated that JAK1 is involved in IL-2, IL-4, IL-6, IL-15 and IFN signaling. UPA-inhibited JAK-STAT ameliorates IFN-γ and IL-6, implicated in MC pathogenesis. Data here supports UPA use in steroid and biologic refractory MC. Further large-scale studies are warranted to delineate long term efficacy and safety of UPA in MC.

Table 1 Demographics and Baseline Disease Characteristics.

Table 2 Trends in clinical parameters at baseline versus Weeks 8 and 16

Table 3 Percentage reduction in loose bowel movements (LBM) and fecal calprotectin (FC)