Alicaforsen, an Antisense Inhibitor of Intercellular Adhesion Molecule-1, in the Treatment for Left-Sided Ulcerative Colitis and Ulcerative Proctitis

Dig Dis. 2018;36(2):123-129. doi: 10.1159/000484979. Epub 2017 Dec 5.

Abstract

Background: Data on the efficacy of intercellular adhesion molecule-1 antisense oligonucleotide alicaforsen in ulcerative colitis (UC) is inconsistent.

Methods: All patients, who had received at least one dose of alicaforsen, were analyzed retrospectively. Alicaforsen's efficacy was assessed in patients treated for left-sided UC and proctitis by comparing clinical and (if applicable) endoscopic disease activity before/after treatment.

Results: Twelve patients were treated for left-sided UC or proctitis. Eleven patients received a 6-week course of a once-daily 240 mg alicaforsen enema formulation. In 1 patient, treatment was discontinued, because it was found to be inefficient. Disease activity measured by the partial Mayo score and 6-point symptom score was significantly reduced after treatment (6.0 vs. 2.4, p = 0.011 and 3.7 vs. 1.4, p = 0.008). Faecal calprotectin showed a trend towards reduction (484.4 vs. 179.5 μg/g, p = 0.063). Clinical improvement was achieved in 10 patients (83.3%). In 7 patients, a relapse occurred (70%). Median duration of clinical improvement was 18.0 weeks (range 1-112). Three patients showed an ongoing improvement of >9 months. No adverse events were reported.

Conclusions: A 6-week course of alicaforsen seemed to be safe and efficacious in inducing clinical improvement in patients with left-sided UC and proctitis. Prolonged clinical improvement was observed in many but not all patients.

Keywords: Alicaforsen; Antisense oligonucleotide; Inflammatory bowel disease; Left-sided ulcerative colitis; Relapse; Ulcerative proctitis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Colitis, Ulcerative / drug therapy*
  • Demography
  • Female
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Oligonucleotides, Antisense / therapeutic use*
  • Phosphorothioate Oligonucleotides / therapeutic use*
  • Proctitis / drug therapy*
  • Treatment Outcome
  • Young Adult

Substances

  • Gastrointestinal Agents
  • Oligonucleotides, Antisense
  • Phosphorothioate Oligonucleotides
  • Intercellular Adhesion Molecule-1
  • alicaforsen