https://orcid.org/0000-0002-2536-5538
Introduction
Microscopic colitis (MC) is an inflammatory disorder of the colon histologically subclassified into lymphocytic colitis (LC) and collagenous colitis (CC).1,2 Budesonide is an effective first-line treatment in both forms of MC. However treatment-refractory disease, particularly in CC, remains a challenging clinical problem.3,4 Janus kinase (JAK) inhibitors are novel small molecules approved for the management of ulcerative colitis that have a rational mechanistic basis for treatment of MC based on the role of interferon-γ in disease pathogenesis.5 One recent case report described the use of upadacitinib, a selective JAK1 inhibitor, in LC.6,7 However, to date no reports exist about the effectiveness of JAK inhibitors for refractory CC. Here, we describe a patient with refractory CC who rapidly achieved clinical remission on upadacitinib.
Case
The patient was a 75-year-old woman with a history of hypothyroidism who developed watery diarrhea (4-8 bowel movements per day, Bristol Stool Scale type 7) accompanied by fecal incontinence in 2014. She was diagnosed with CC based on colonoscopy with biopsies, after ruling out celiac disease and infectious etiologies. Treatment with budesonide, cholestyramine, bismuth subsalicylate, loperamide, and later prednisone 40 mg daily resulted in a slight decrease in stool frequency, but she continued to experience urgent liquid stools and fecal incontinence that greatly impaired her quality of life. She was next treated with dose-optimized adalimumab, vedolizumab, and ustekinumab without meaningful improvement (Figure 1). Because of her refractory symptoms, she was started on upadacitinib 45 mg daily, with achievement of clinical remission by Hjortswang criteria8 for the first time since diagnosis within 1 week of therapy initiation (Figure 1). After 8 weeks of induction dosing, she had 1 to 2 formed (Bristol Stool Scale type 3-5) bowel movements per day with complete resolution of urgency and incontinence. C-reactive protein decreased from 1.1 to <0.1 mg/dL and erythrocyte sedimentation rate from 7 to 3 mm/h. Monitoring labs showed an increase in her transaminases (alanine transaminase from 21 to 40 IU/L and aspartate transaminase from 19 to 40 IU/L) and a drop in hemoglobin (from 13.2 to 11.2 g/dL). Her upadacitinib dose was decreased to 30 mg, then 15 mg daily. On this dose she has remained in clinical remission with hemoglobin normalization and stable transaminases.
Collagenous colitis disease activity trend over time by biologic and small molecule treatment regimen.
This case report illustrates the successful use of the selective JAK1 inhibitor upadacitinib for the treatment of therapy refractory CC. Prospective studies are needed to evaluate the efficacy and long-term safety of upadacitinib for refractory LC and CC.
Funding
K.E.B. was funded by National Institutes of Health grant K23DK131366
Conflict of Interest
L.B. reports no conflicts. K.E.B. has received consulting fees from Bristol Myers Squibb and OM1.
