Researchers from Canada and the USA evaluated the safety and efficacy of the intercellular adhesion molecule 1 (ICAM-1) antisense phosphorothioate oligonucleotide, alicaforsen (ISIS 2302), in Crohn's disease.
A total of 299 active (Crohn's disease activity index (CDAI) 200-350), steroid-dependent (prednisone 10-40 mg) Crohn's patients were included in the study.
The patients had a mean baseline CDAI of 276 and steroid dose of 23 mg/day.
Individuals were randomized into 3 treatment groups. These were placebo versus alicaforsen (2 mg/kg intravenously 3 times a week) for 2 or 4 weeks.
Patients were treated in months 1 and 3, with steroid withdrawal attempted by week 10.
|Successful steroid withdrawal:|
The primary end point (steroid-free remission) was a CDAI < 150, off steroids at the end of week 14.
The authors found that rates of steroid-free remission were equivalent for the 2- and 4-week alicaforsen groups (20% and 21%) and the placebo group (19%).
At week 14, steroid withdrawal was successful in more alicaforsen patients compared with placebo treated patients (78% vs 64%).
Steroid-free remission was highly correlated with exposure. Other clinical responses were also correlated with exposure.
CDAI scores decreased by 136 at week 14 versus 52 for placebo. In addition, inflammatory bowel disease questionnaire score improved by 43 versus 15 points for placebo.
Dr Bruce Yacyshyn, of the University of Alberta, Edmonton, Alberta, Canada, concluded on behalf of his colleagues, "Although the primary outcomes failed to demonstrate efficacy, pharmacodynamic modeling suggests that alicaforsen (ISIS 2302) may be an effective therapy for steroid-dependent Crohn's disease."