JAK inhibitor, a new player for treatment-refractory microscopic colitis.

Abstract

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 411 Informed consent has been obtained. Rheumatoid arthritis was diagnosed and treated conventionally with steroids, nonsteroidal inflammatory drugs and methotrexate. A decreased vascular colonic pattern was observed during endoscopy while histologic evaluation showed both an increased number of inflammatory cells within the lamina propria and increased intraepithelial CD3 positive lymphocytes revealing a diagnosis of LC. Nonsteroidal therapy was reduced when the diagnosis of LC was made. She was not receiving any other medication. Budesonide and systemic corticosteroids (prednisolone up to 20 mg/day) had no effect on the diarrhea. After 12 months, anti-TNF therapy was started for her rheumatoid arthritis but this also had no impact on the diarrhea. Diarrhea persisted, with a substantial effect on her quality of life, as did LC, confirmed histologically (no fewer than 5 procedures over 4 years), until her rheumatoid arthritis lost response to anti-TNF therapy. To offer better control of the rheumatoid condition, she was then switched to upadacitinib (UPA), a selective Janus kinase inhibitor-1 (JAK 1) inhibitor (15 mg once daily) and unexpectedly, her diarrhea resolved within days. Endoscopic evaluation 5 months after UPA initiation revealed a normal mucosa and complete normalization of the histologic lesions. Sixteen months after initiation, the patient remains free of diarrhea and continues UPA 15 mg/day. The etiology and pathophysiology of MC are not well understood but MC shows a T-helper 1 (Th1) mucosal cytokine profile. Interferon-γ (IFN-γ) is the dominant cytokine in CC, but TNF-α in LC, together with increased mRNA levels of interleukin (IL)-8 and IL-15. There is also evidence of a mixed pISSN 1598-9100 • eISSN 2288-1956 https://doi.org/10.5217/ir.2023.00030 Intest Res 2023;21(3):411-412