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Optimal Dosing of Immunomodulating Drugs: A Dose-Comparison Study of GA in RRMS

Published online by Cambridge University Press:  22 October 2007

Daniel Wynn ,
Catherine Meyer ,
Neil Allen  and
Dennis O'Brien
Daniel Wynn
Affiliation:
Consultants in Neurology, Northbrook, IL, USA; Email: [email protected]
Catherine Meyer
Affiliation:
Consultants in Neurology, Northbrook, IL, USA; Email: [email protected]
Neil Allen
Affiliation:
Consultants in Neurology, Northbrook, IL, USA; Email: [email protected]
Dennis O'Brien
Affiliation:
Billings Clinic, Billings, MT, USA
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Extract

ABSTRACT

Background: Though indications of a dose–response for glatiramer acetate (GA) were apparent during early drug development and clinical testing, no formal dose-comparisons of GA had been conducted before the present study. Design/Methods: This multicenter, randomized, double-blind study compared the safety and efficacy of two GA doses: 20 mg/day, the currently approved dose, versus 40 mg/day. Relapsing–remitting multiple sclerosis (RRMS) patients with active disease (1–15 gadolinium-enhancing (GdE) lesions on screening magnetic resonance imaging (MRI) and ≥1 relapse in the previous year) were eligible. The primary outcome was change from baseline in total number of GdE lesions at 7, 8, and 9 months. Other outcomes included effects on relapse, changes in expanded disability status scale (EDSS) scores, and responder analyses. Results: Benefits of the 40 mg GA dose versus the 20 mg dose on GdE lesions were evident by month 3. Additionally, significant advantages of the 40 mg dose were observed for time to first relapse and proportion of relapse-free patients. There was a trend for better outcomes with 40 mg/day GA for the primary efficacy measure, but the difference between doses was not statistically significant. Both GA doses were safe and similarly well tolerated. Interpretation: A 40 mg/day GA dosage may be more effective than the 20 mg/day recommended dosage for reducing disease activity, and appears to have an earlier onset of action. A large, phase III study is underway to confirm these findings.

Keywords

dose–responseglatiramer acetatemultiple sclerosisrelapsing–remitting.
Type
Research Article
Information
Progress in Neurotherapeutics and Neuropsychopharmacology , Volume 3 , Issue 1 , January 2008 , pp. 137 - 151
Copyright
© 2008 Cambridge University Press

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