Document Detail


Boosting endogenous neuroprotection in multiple sclerosis: the ASsociation of Inosine and Interferon beta in relapsing- remitting Multiple Sclerosis (ASIIMS) trial.
MedLine Citation:
PMID:  20200198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Anti-inflammatory drugs are effective on relapses, but neuroprotective agents to prevent disability are still unavailable. Uric acid has neuroprotective effects in experimental models including encephalomyelitis and appears to be involved in multiple sclerosis. Oral administration of inosine, a precursor of uric acid, increases serum uric acid levels and is well tolerated. Our objective was to test the possibility that a combination therapy associating an anti-inflammatory drug (interferon beta) and an endogenous neuroprotective molecule (uric acid) would be more effective than interferon beta alone on the accumulation of disability. Patients with relapsing-remitting multiple sclerosis on interferon beta for at least 6 months were randomized to interferon beta + inosine or interferon beta + placebo for 2 years. The dose of inosine was adjusted to maintain serum uric acid levels in the range of asymptomatic hyperuricaemia (<or=10 mg/dl). The primary end points were percentage of patients with progression of disability and time to sustained progression (Kaplan-Meier analysis). The combination of interferon beta and inosine was safe and well tolerated but did not provide any additional benefit on accumulation of disability compared with interferon beta alone. We conclude that endogenous neuroprotective mechanisms recently identified in multiple sclerosis are complex and uric acid does not reflect the entire story.
Authors:
Richard E Gonsette; Christian Sindic; Marie B D'hooghe; Peter-Paul De Deyn; Robert Medaer; Alex Michotte; Pierrette Seeldrayers; Daniel Guillaume;
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-03-03
Journal Detail:
Title:  Multiple sclerosis (Houndmills, Basingstoke, England)     Volume:  16     ISSN:  1477-0970     ISO Abbreviation:  Mult. Scler.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-13     Completed Date:  2010-07-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9509185     Medline TA:  Mult Scler     Country:  England    
Other Details:
Languages:  eng     Pagination:  455-62     Citation Subset:  IM    
Affiliation:
National Centre for Multiple Sclerosis, Vanheylenstraat 16, Melsbroek, Belgium. r.gonsette@skynet.be
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-Inflammatory Agents / adverse effects,  therapeutic use*
Belgium
Disability Evaluation
Disease Progression
Double-Blind Method
Drug Therapy, Combination
Female
Humans
Inosine / adverse effects,  metabolism,  therapeutic use*
Interferon-beta / adverse effects,  therapeutic use*
Kaplan-Meiers Estimate
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting / blood,  diagnosis,  drug therapy*
Neuroprotective Agents / adverse effects,  metabolism,  therapeutic use*
Severity of Illness Index
Time Factors
Treatment Outcome
Uric Acid / blood
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Neuroprotective Agents; 145155-23-3/interferon beta-1b; 145258-61-3/interferon beta 1a; 58-63-9/Inosine; 69-93-2/Uric Acid; 77238-31-4/Interferon-beta
Investigator
Investigator/Affiliation:
R E Gonsette / ; C Sindic / ; S Goffette / ; V van Pesch / ; T Duprez / ; P Demaerel / ; M B D'hooghe / ; G Nagels / ; M Descamps / ; A Van Remoortel / ; M C Deville / ; A van Nunen / ; R Medaer / ; E Vanroose / ; A Bogaerts / ; A Michotte / ; V Bissay / ; M De Boeck / ; P De Deyn / ; R Sheorajpanday / ; E Braxel / ; P Seeldrayers / ; J Jacquy / ; T Piette / ; C De Cock / ; D Guillaume / ; R Reznik / ; R Metz / ; A Maertens de Noordhout / ; V Delvaux / ; M Dupuis / ; P Cras / ; B Willekens / ; H Timperman / ; D Decoo / ; M De Sutter / ; M Van Zandijcke / ; I Dehaene / ; K Verhoeven / ; O Deryck / ; J Casselman / ; A Criel / ; V Schotte / ; R Verhaeghe / ; C Dusautoir / ; L Hermoye / ; F Maes /

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