Alicaforsen, an antisense inhibitor of ICAM-1, as treatment for chronic refractory pouchitis after proctocolectomy: A case series

Background and aims: The published data about the efficacy of the intercellular adhesion molecule-1 (ICAM-1) antisense oligonucleotide termed alicaforsen in inflammatory bowel disease (IBD) is rather inconsistent. This case series analyzes its efficacy in chronic refractory pouchitis, after proctocolectomy. Methods: We performed a retrospective analysis on all patients who had received at least one dose of alicaforsen for IBD at three referral centers in Switzerland. We assessed the drug's efficacy in patients treated for chronic refractory pouchitis, by comparing the clinical and/or endoscopic disease activity at baseline with a 2-3-month follow-up visit. Results: We identified 22 patients who had received at least one dose. Among them, 13 patients were being treated for chronic refractory pouchitis. These patients had a median age of 38.0 years (95% CI 21.0-69.0) and five were female (38.5%). The median time since pouch surgery was 102.5 months (95% CI 16.0-288.0), with a median pouchitis duration of 16.0 months (95% CI 4.0-216.0). At 2-3 months after therapy, clinical and endoscopic disease activity was significantly reduced (stool frequency 9.0 versus 6.0, the Pouchitis Disease Activity Index (PDAI) clinical subscore was 4.0 versus 1.0, and the endoscopic disease activity was 4.0 versus 2.0). Clinical improvement was achieved in 11 out of 13 pouchitis patients (84.6%); however, a relapse was observed in nine of these patients (81.8%). The median time from clinical improvement to relapse was 16 weeks (95% CI 9.0-23.0). Conclusions: Alicaforsen seemed to be efficacious in inducing clinical and/or endoscopic improvement in chronic refractory pouchitis and may be a promising treatment alternative in those patients; however, given the high proportion of relapse, one 6-week course of alicaforsen may not be sufficient.