Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease
2001; Elsevier BV; Volume: 120; Issue: 6 Linguagem: Inglês
10.1053/gast.2001.24015
ISSN1528-0012
AutoresStefan Schreiber, Susanna Nikolaus, H Malchow, Wolfgang Kruis, Herbert Lochs, Andreas Raedler, Eckhart G. Hahn, Thomas Krummenerl, Gerhard Steinmann,
Tópico(s)Immunodeficiency and Autoimmune Disorders
ResumoBackground & Aims: ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD). Methods: 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 placebo patients reached the primary endpoint. Steroid-free remission at week 26 (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 26 (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%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302–treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups. Conclusions: The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.GASTROENTEROLOGY 2001;120:1339-1346
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