Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease

Background & Aims: ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Cro hn's disease in a pilot trial. The aim of this study was to investigate saf ety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD), Met hods: A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI < 150) at week 14, Results: Only 2 of 60 (3.3%) ISIS-2302-treated and no plac ebo patients reached the primary endpoint, Steroid-free remission at week 2 6 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose < 10 mg/day at weeks 14 and 2 6 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3%vs. 6.7%, respectivel y]), Treatment with ISIS-2302 was safe. The most common side effects were i njection site reactions in the active treatment group (23% in ISIS-2302-tre ated patients vs. none in placebo patients). No statistically significant d ifferences in the frequency of side effects were detected between dose grou ps, Conclusions: The trial did not prove clinical efficacy of ISIS-2302 bas ed on the primary endpoint. Positive trends were observed in some of the se condary endpoints.