https://orcid.org/0000-0003-3558-7123
To the Editors,
Collagenous colitis [CC] is a subtype of microscopic colitis [MC] typically affecting middle-aged and elderly women accompanied by persistent watery diarrhoea. Diagnosis relies on histological observations, specifically thickening of the subepithelial collagen band [SECB] beneath the colonic epithelium.1 The aetiology of CC is unknown, but genetics, environmental factors, and drugs such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and serotonin selective receptor inhibitors are suspected triggers. Discontinuing the implicated drugs often alleviates symptoms. In cases unrelated to drugs, corticosteroids are prescribed but treatment can be challenging.
Janus kinase [JAK] inhibitors are novel small molecules approved for the management of inflammatory bowel disease [IBD] that have a rational mechanistic basis for treatment of CC based on the role of interferon-γ in disease pathogenesis.2 Recent case reports have described the use of JAK inhibitors tofacitinib and upadacitinib for MC.3–5 While three JAK inhibitors are available for IBD, filgotinib has fewer adverse events than upadacitinib and tofacitinib. However, there are currently no data on filgotinib’s efficacy in treating refractory CC. We herein report a patient with medically refractory CC successfully treated with the selective JAK1 inhibitor, filgotinib, leading to rapid clinical remission.
A 54-year-old woman was diagnosed with CC at the age of 48 years, following persistent watery diarrhoea, as confirmed by colonoscopy with biopsies. She had no medications that caused CC. Treatment with mesalazine, cholestyramine, ramosetron hydrochloride, and loperamide had been only intermittently successful. Corticosteroid 30 mg daily was added due to worsening of watery diarrhoea [seven to nine bowel movements per day]. Bowel movements improved to almost normal. However, when the steroid dose was reduced, the diarrhoea recurred. She had a cys/cys mutation in the NUDT15 gene and was unable to use thiopurines. A re-colonoscopy was performed which showed no inflammation with a visible vascular pattern throughout the entire colon. As expected, non-targeted colon biopsies obtained during the colonoscopy [and multiple prior examinations] showed an increase in the SECB, consistent with CC [Figure 1]. Filgotinib 200 mg once daily was initiated, and the diarrhoea improved within 2 weeks. At week 3 after starting therapy, she reported passing one formed stool a day. Total protein [TP] increased from 4.5 to 5.6 g/dL and albumin increased from 2.8 to 3.8 g/dL. By 5 weeks, she was able to achieve steroid-free remission. Afterward, TP improved to 6.0 g/dL and albumin normalized to 4.0 g/dL, and she has continued with treatment without any adverse events.
Haematoxylin and eosin stain (×200) of a non-targeted biopsy of the colon which resulted in the diagnosis of CC before filgotinib treatment. Marked deposition of collagen fibres is visible beneath the superficial layer.
This is the first case report of the successful use of the JAK1 inhibitor, filgotinib, in treating therapy-refractory CC. Further prospective studies are required to assess its effectiveness and long-term safety in managing refractory CC.
Funding
No funding was provided for this case report.
Conflicts of Interest
None of the authors has a conflict of interest.
Author Contributions
TS and AN conceived the study. TS and AN wrote the manuscript and created the figure. TS and AN revised the manuscript. Both authors approved the final version of the manuscript.
Data Availability
Raw data were generated at Juntendo University. Derived data supporting the findings of this study are available from the corresponding author TS on request.
