Abstract | OBJECTIVE: METHODS: This was a randomised, placebo controlled, double blind, escalating dose multicentre study in 40 patients with mild to moderately active distal ulcerative colitis (disease activity index (DAI) 4-10). Patients were assigned to four dosing cohorts of 10 patients each (eight active, two placebo). Each patient received 60 ml of alicaforsen enema (0.1, 0.5, 2, or 4 mg/ml or placebo) once daily for 28 consecutive days. Safety and efficacy (DAI and clinical activity index) scores were evaluated up to six months after initiation of dosing. RESULTS: At day 29, alicaforsen enema resulted in dose dependent improvement in DAI (overall p = 0.003). Alicaforsen 4 mg/ml improved DAI by 70% compared with the placebo response of 28% (p = 0.004). Alicaforsen 2 and 4 mg/ml improved DAI status by 72% and 68% compared with a placebo response of 11.5% at month 3 (p = 0.016 and 0.021, respectively). Specifically, DAI improved from 5.6 to 1.6 and from 6.3 to 2.5 in the 2 and 4 mg/ml groups compared with placebo (7.5 to 6.1). None of the patients in the 4 mg/ml group compared with 4/8 placebo patients required additional medical or surgical intervention over baseline during the six month period after starting the enema treatment. The safety profile was favourable. CONCLUSIONS:
Alicaforsen enema showed promising acute and long term benefit in patients with mild to moderate descending ulcerative colitis. Alicaforsen enemas had a favourable safety profile. These findings require verification in larger randomised controlled clinical trials.
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Authors | S J H van Deventer, J A Tami, M K Wedel |
Journal | Gut
(Gut)
Vol. 53
Issue 11
Pg. 1646-51
(Nov 2004)
ISSN: 0017-5749 [Print] England |
PMID | 15479686
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Gastrointestinal Agents
- Oligodeoxyribonucleotides, Antisense
- Phosphorothioate Oligonucleotides
- Thionucleotides
- Intercellular Adhesion Molecule-1
- alicaforsen
|
Topics |
- Adult
- Colitis, Ulcerative
(drug therapy)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Enema
- Female
- Gastrointestinal Agents
(administration & dosage, adverse effects, therapeutic use)
- Humans
- Intercellular Adhesion Molecule-1
(immunology)
- Male
- Middle Aged
- Oligodeoxyribonucleotides, Antisense
(administration & dosage, adverse effects, therapeutic use)
- Phosphorothioate Oligonucleotides
- Severity of Illness Index
- Thionucleotides
(administration & dosage, adverse effects, therapeutic use)
- Treatment Outcome
|