Treatment of antibiotic refractory chronic pouchitis with JAK inhibitors and S1P receptor modulators: an ECCO CONFER Multicentre Case Series

Davide Giuseppe Ribaldone; Giulia Testa; Bram Verstockt; Tamas Molnar; Edoardo Savarino; Carsten Schmidt; Sophie Vieujean; Niels Teich; Corina Meianu; Pascal Juillerat; Nathan Grellier; Triana Lobaton

doi:10.1093/ecco-jcc/jjad194

Treatment of antibiotic refractory chronic pouchitis with JAK inhibitors and S1P receptor modulators: an ECCO CONFER Multicentre Case Series

J Crohns Colitis. 2023 Nov 15:jjad194. doi: 10.1093/ecco-jcc/jjad194. Online ahead of print.

Authors

Davide Giuseppe Ribaldone¹, Giulia Testa², Bram Verstockt^{3

4}, Tamas Molnar⁵, Edoardo Savarino⁶, Carsten Schmidt^{7

8}, Sophie Vieujean⁹, Niels Teich^{8

10}, Corina Meianu^{11

12}, Pascal Juillerat^{13

14}, Nathan Grellier¹⁵, Triana Lobaton¹⁶

Affiliations

¹ Department of Medical Sciences, Division of Gastroenterology, University of Turin, Turin, Italy.
² Gastroenterology-U, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.
³ Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
⁴ Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
⁵ University of Szeged, Hungary.
⁶ Division of Gastroenterology, Department of Surgery Oncology and Gastroenterology DiSCOG, University of Padova, Padova, Italy.
⁷ Medical Clinic II, Hospital Fulda, Fulda, Germany.
⁸ Medical Faculty of the Friedrich Schiller University, Jena, Germany.
⁹ Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium.
¹⁰ Gastroenterology Practice, Leipzig, Germany.
¹¹ Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
¹² Gastroenterology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania.
¹³ Clinic for Visceral Surgery and Medicine, Department of Gastroenterology, Bern University Hospital.
¹⁴ Crohn and Colitis Center, Gastro-enterologie Beaulieu SA, Lausanne, Switzerland.
¹⁵ Hepato-Gastroenterology Department, University Hospital of Poitiers, Poitiers, France.
¹⁶ Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium.

PMID: 37965867
DOI: 10.1093/ecco-jcc/jjad194

Abstract

Background and aims: Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in antibiotic refractory chronic pouchitis (CARP) are lacking.

Methods: This ECCO-CONFER project retrospectively collected JAK inhibitors or S1P receptor modulators treatments for CARP with at least 3-months follow up. The outcomes included corticosteroid and antibiotics-free clinical response and remission at three and twelve months, trend in mPDAI, endoscopic PDAI, CRP and calprotectin.

Results: Seventeen treatments in 15 patients were collected. Previous pouchitis treatments included infliximab (5/15), adalimumab (4/15), vedolizumab (9/15), and ustekinumab (5/15). Pooling data on JAK inhibitors (8 tofacitinib, 1 filgotinib and 6 upadacitinib), after 3 months (T3), steroid and antibiotics-free clinical response was achieved in 53.3% (8/15), steroid and antibiotics-free clinical remission was achieved in 40% (6/15). Of the patients with at least 12 months of follow-up, steroid and antibiotics-free clinical response was achieved in 50% (3/6) and remission in one patient (16.7%), endoscopic response in 50% (3/6), endoscopic remission in 50% (3/6). Of the two ozanimod treatments at T3, steroid and antibiotics-free clinical response was achieved in one patient, without remission; both discontinued ozanimod before T12. No side effects reported.

Conclusions: Small molecules may represent a suitable option for CARP refractory to multiple biologics, deserving further investigation.

Keywords: biologics; filgotinib; ozanimod; pouchitis; small molecules; target therapy; tofacitinib; ulcerative colitis; upadacitinib.