{"title":"JAK抑制剂,治疗难治性显微结肠炎的新药物。","authors":"Anne Druez, Simon Travis, Jean-François Rahier","doi":"10.5217/ir.2023.00030","DOIUrl":null,"url":null,"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. 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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. 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JAK inhibitor, a new player for treatment-refractory microscopic colitis.
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
期刊介绍:
Intestinal Research (Intest Res) is the joint official publication of the Asian Organization for Crohn''s and Colitis (AOCC), Chinese Society of IBD (CSIBD), Japanese Society for IBD (JSIBD), Korean Association for the Study of Intestinal Diseases (KASID), Taiwan Society of IBD (TSIBD) and Colitis Crohn''s Foundation (India) (CCF, india). The aim of the Journal is to provide broad and in-depth analysis of intestinal diseases, especially inflammatory bowel disease, which shows increasing tendency and significance. As a Journal specialized in clinical and translational research in gastroenterology, it encompasses multiple aspects of diseases originated from the small and large intestines. The Journal also seeks to propagate and exchange useful innovations, both in ideas and in practice, within the research community. As a mode of scholarly communication, it encourages scientific investigation through the rigorous peer-review system and constitutes a qualified and continual platform for sharing studies of researchers and practitioners. Specifically, the Journal presents up-to-date coverage of medical researches on the physiology, epidemiology, pathophysiology, clinical presentations, and therapeutic interventions of the intestinal diseases. General topics of interest include inflammatory bowel disease, colon and small intestine cancer or polyp, endoscopy, irritable bowel syndrome and other motility disorders, infectious enterocolitis, intestinal tuberculosis, and so forth. The Journal publishes diverse types of academic materials such as editorials, clinical and basic reviews, original articles, case reports, letters to the editor, brief communications, perspective, statement or commentary, and images that are useful to clinicians and researchers.