Treatment of Antibiotic Refractory Chronic Pouchitis With JAK Inhibitors and S1P Receptor Modulators: An ECCO CONFER Multicentre Case Series

Background and Aims Data regarding the effectiveness and safety of Janus kinase [JAK] inhibitors and sphingosine-1-phosphate [S1P] receptor modulators in antibiotic refractory chronic pouchitis [CARP] are lacking.Methods This ECCO-CONFER project retrospectively collected data for JAK inhibitor or S1P receptor modulator treatments for CARP with at least 3 months of follow-up. The outcomes included corticosteroid- and antibiotic-free clinical response and remission at 3 and 12 months, and trends in modified pouchitis disease activity index [mPDAI], endoscopic PDAI, C-reactive protein, and calprotectin.Results Seventeen treatments in 15 patients were evaluated. Previous pouchitis treatments included infliximab [5/15], adalimumab [4/15], vedolizumab [9/15], and ustekinumab [5/15]. Pooling data on JAK inhibitors [eight tofacitinib, one filgotinib, and six upadacitinib] after 3 months [T3], steroid- and antibiotic-free clinical response was achieved in 53.3% [8/15], and steroid- and antibiotic-free clinical remission was achieved in 40% [6/15]. Of the patients with at least 12 months of follow-up, steroid- and antibiotic-free clinical response was achieved in 50% [3/6] and remission in one patient [16.7%], endoscopic response in 50% [3/6], and endoscopic remission in 50% [3/6]. Of the two ozanimod treatments at T3, steroid- and antibiotic-free clinical response was achieved in one patient, without remission; both discontinued ozanimod before T12. No side effects were reported.Conclusions Small molecules may represent a suitable option for CARP refractory to multiple biologics, deserving further investigation.

Automated summary

There is a lack of data on the effectiveness and safety of Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators in antibiotic refractory chronic pouchitis (CARP). This study retrospectively collected data on JAK inhibitor or S1P receptor modulator treatments for CARP and found that small molecules may be a suitable option for CARP refractory to multiple biologics, but further investigation is warranted.