Ustekinumab Rescue Therapy in a Patient With Chronic Refractory Pouchitis

Ustekinumab Rescue Therapy in a Patient With Chronic Refractory Pouchitis Letter Restorative proctocolectomy with ileal pouch anal anastomosis [IPAA] is the treatment of choice in patients with refractory ulcerative colitis [UC].1 A challenging situation in up to 10% of IPAA patients is recurrent or refractory pouchitis.2 Some alternative immunosuppressive therapy options are successful.2 A subset of patients with IPAA may develop Crohn’s disease [CD] or a Crohn’s disease–like condition of the pouch. Therapeutic management of this situation can be challenging. Tran-Minh et al. presented two patients with clinical remission under ustekinumab [UST] therapy.3 We would like to report another patient with suspected CD-like chronic pouchitis with bloody diarrhea, refractory to fecal microbiota transplantation [FMT], anti-TNF therapies and continued steroids. A 40-year-old male patient with bloody diarrhea was diagnosed with UC in 2005. Steroid therapy was initiated. In the further course, a chronic active UC developed, and medication with azathioprine had to be stopped due to pancreatitis as a side effect of azathioprine. Biologics therapy involving infliximab, adalimumab and vedolizumab did not achieve remission. Even treatment with leukocyte apheresis did not reduce the disease activity. Therefore, in January 2015, a colectomy and IPAA was performed. In the further course stenosis of the anastomosis and refractory pouchitis occurred. Various antibiotic treatments did not lead to any improvement, but surgical complications in the form of fistulae or abscesses were excluded. Four FMTs in an interval of 4 weeks failed to produce clinical improvement. Due to the therapy-resistant pouchitis, including failure of antibiotic treatment, FMT, and a steroid-dependent course, and additionally on the basis of an endoscopic image indicating mucosal erythema, ulcerations, loss of vascular pattern, and granularity of pouch mucosa, induction therapy with UST in combination with 50 mg prednisolone was initiated in April 2017 [Week 0]. At this time, the histology assumed a CD-like disease in the pouch and neoterminal ileum. No NOD2 mutations [rs2066844, rs2066845 or rs2066847] were found. After initiation of UST 390 mg parenterally at Week 0, the patient was followed up as an outpatient every 4 weeks. He reported improvement in clinical symptoms at Week 4. Frequency of defecation decreased from 20 bowel movements to 8–10/day without blood or mucus. Pouchoscopy on Week 8 demonstrated significant improvement [Figure 1]. Serum CRP and fecal calprotectin in the stool also normalized on repeated testing. After 6 months, prednisolone was able to be reduced to 5 mg per day. Figure 1. View largeDownload slide A1 shows the chronic refractory pouchitis at the time of initiating UST [PDAI 12], A2 shows the pouch in Week 4, and A3 shows the pouch in Week 12 [PDAI 6]. B1 and B2 show the histological aspects of chronic inflammation featuring CD-like disease. Figure 1. View largeDownload slide A1 shows the chronic refractory pouchitis at the time of initiating UST [PDAI 12], A2 shows the pouch in Week 4, and A3 shows the pouch in Week 12 [PDAI 6]. B1 and B2 show the histological aspects of chronic inflammation featuring CD-like disease. The etiology of pouchitis is still not fully understood. Therapy, especially therapy of chronic pouchitis, remains challenging. In an earlier case series, we showed beneficial effects with FMTs in three out of five patients, and our report suggests that UST might be a treatment option worthy of consideration.4 Clinical trials are warranted to assess the efficacy and safety of UST in this patient group. Funding The data have been generated during routine work. Conflict of Interest JP has no conflict of interests; JZ has no conflict of interests; AS has received lecture fees and travel accommodation from AbbVie, Falk-Foundation, Janssen, MSD, Mundipharma, and Takeda. AS has received consulting fees from AbbVie, Astellas, Biogen, Janssen, MSD, Mundipharma, Shield Therapeutics, Summit Therapeutics, and Takeda. Author Contributions JP: writing of the first draft of the manuscript; JZ: writing and correction of the manuscript; AS: data collection, writing and correction of the manuscript. References 1. Lightner AL , Mathis KL , Dozois EJ et al. Results at up to 30 years after ileal pouch–anal anastomosis for chronic ulcerative colitis . Inflamm Bowel Dis 2017 ; 23 : 781 – 90 . Google Scholar CrossRef Search ADS PubMed 2. Herfarth HH , Long MD , Isaacs KL . Use of biologics in pouchitis: a systematic review . J Clin Gastroenterol 2015 ; 49 : 647 – 54 . Google Scholar CrossRef Search ADS PubMed 3. Tran-Minh ML , Allez M , Gornet JM . Successful treatment with ustekinumab for chronic refractory pouchitis . J Crohns Colitis 2017 ; 11 : 1156 . Google Scholar CrossRef Search ADS PubMed 4. Stallmach A , Lange K , Buening J , Sina C , Vital M , Pieper DH . Fecal microbiota transfer in patients with chronic antibiotic-refractory pouchitis . Am J Gastroenterol 2016 ; 111 : 441 – 3 . Google Scholar CrossRef Search ADS PubMed Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Crohn's and Colitis Oxford University Press

Ustekinumab Rescue Therapy in a Patient With Chronic Refractory Pouchitis

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Publisher
Elsevier Science
Copyright
Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
ISSN
1873-9946
eISSN
1876-4479
D.O.I.
10.1093/ecco-jcc/jjy037
Publisher site
See Article on Publisher Site

Abstract

Letter Restorative proctocolectomy with ileal pouch anal anastomosis [IPAA] is the treatment of choice in patients with refractory ulcerative colitis [UC].1 A challenging situation in up to 10% of IPAA patients is recurrent or refractory pouchitis.2 Some alternative immunosuppressive therapy options are successful.2 A subset of patients with IPAA may develop Crohn’s disease [CD] or a Crohn’s disease–like condition of the pouch. Therapeutic management of this situation can be challenging. Tran-Minh et al. presented two patients with clinical remission under ustekinumab [UST] therapy.3 We would like to report another patient with suspected CD-like chronic pouchitis with bloody diarrhea, refractory to fecal microbiota transplantation [FMT], anti-TNF therapies and continued steroids. A 40-year-old male patient with bloody diarrhea was diagnosed with UC in 2005. Steroid therapy was initiated. In the further course, a chronic active UC developed, and medication with azathioprine had to be stopped due to pancreatitis as a side effect of azathioprine. Biologics therapy involving infliximab, adalimumab and vedolizumab did not achieve remission. Even treatment with leukocyte apheresis did not reduce the disease activity. Therefore, in January 2015, a colectomy and IPAA was performed. In the further course stenosis of the anastomosis and refractory pouchitis occurred. Various antibiotic treatments did not lead to any improvement, but surgical complications in the form of fistulae or abscesses were excluded. Four FMTs in an interval of 4 weeks failed to produce clinical improvement. Due to the therapy-resistant pouchitis, including failure of antibiotic treatment, FMT, and a steroid-dependent course, and additionally on the basis of an endoscopic image indicating mucosal erythema, ulcerations, loss of vascular pattern, and granularity of pouch mucosa, induction therapy with UST in combination with 50 mg prednisolone was initiated in April 2017 [Week 0]. At this time, the histology assumed a CD-like disease in the pouch and neoterminal ileum. No NOD2 mutations [rs2066844, rs2066845 or rs2066847] were found. After initiation of UST 390 mg parenterally at Week 0, the patient was followed up as an outpatient every 4 weeks. He reported improvement in clinical symptoms at Week 4. Frequency of defecation decreased from 20 bowel movements to 8–10/day without blood or mucus. Pouchoscopy on Week 8 demonstrated significant improvement [Figure 1]. Serum CRP and fecal calprotectin in the stool also normalized on repeated testing. After 6 months, prednisolone was able to be reduced to 5 mg per day. Figure 1. View largeDownload slide A1 shows the chronic refractory pouchitis at the time of initiating UST [PDAI 12], A2 shows the pouch in Week 4, and A3 shows the pouch in Week 12 [PDAI 6]. B1 and B2 show the histological aspects of chronic inflammation featuring CD-like disease. Figure 1. View largeDownload slide A1 shows the chronic refractory pouchitis at the time of initiating UST [PDAI 12], A2 shows the pouch in Week 4, and A3 shows the pouch in Week 12 [PDAI 6]. B1 and B2 show the histological aspects of chronic inflammation featuring CD-like disease. The etiology of pouchitis is still not fully understood. Therapy, especially therapy of chronic pouchitis, remains challenging. In an earlier case series, we showed beneficial effects with FMTs in three out of five patients, and our report suggests that UST might be a treatment option worthy of consideration.4 Clinical trials are warranted to assess the efficacy and safety of UST in this patient group. Funding The data have been generated during routine work. Conflict of Interest JP has no conflict of interests; JZ has no conflict of interests; AS has received lecture fees and travel accommodation from AbbVie, Falk-Foundation, Janssen, MSD, Mundipharma, and Takeda. AS has received consulting fees from AbbVie, Astellas, Biogen, Janssen, MSD, Mundipharma, Shield Therapeutics, Summit Therapeutics, and Takeda. Author Contributions JP: writing of the first draft of the manuscript; JZ: writing and correction of the manuscript; AS: data collection, writing and correction of the manuscript. References 1. Lightner AL , Mathis KL , Dozois EJ et al. Results at up to 30 years after ileal pouch–anal anastomosis for chronic ulcerative colitis . Inflamm Bowel Dis 2017 ; 23 : 781 – 90 . Google Scholar CrossRef Search ADS PubMed 2. Herfarth HH , Long MD , Isaacs KL . Use of biologics in pouchitis: a systematic review . J Clin Gastroenterol 2015 ; 49 : 647 – 54 . Google Scholar CrossRef Search ADS PubMed 3. Tran-Minh ML , Allez M , Gornet JM . Successful treatment with ustekinumab for chronic refractory pouchitis . J Crohns Colitis 2017 ; 11 : 1156 . Google Scholar CrossRef Search ADS PubMed 4. Stallmach A , Lange K , Buening J , Sina C , Vital M , Pieper DH . Fecal microbiota transfer in patients with chronic antibiotic-refractory pouchitis . Am J Gastroenterol 2016 ; 111 : 441 – 3 . Google Scholar CrossRef Search ADS PubMed Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

Journal of Crohn's and ColitisOxford University Press

Published: Aug 1, 2018

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