Date of Award

Fall 2011

Degree Type


Degree Name

Master of Science (MSc)


Health Research Methodology


Feng Xie


Eleanor Pullenayegum



Committee Member

Ron Goeree



Oral pharmacotherapy has the potential to offer multiple sclerosis patients improved clinical outcomes compared to traditional therapies.


This review assesses the effects of oral therapies compared to placebo and interferon beta-1a in adults with relapsing-remitting multiple sclerosis (RRMS).

Search methods

We searched the MEDLINE, EMBASE, Cochrane Library, Web of Science (January 1980 to April 2011) and clinincaltrials.gov (April 2011) databases and reference lists of articles. The FDA website was also searched.

Selection criteria

Double-blind, placebo-controlled, randomized trials of RRMS patients who were treated with fingolimod, cladribine, laquinimod or interferon beta-1a.

Data collection and analysis

Two reviewers independently assessed articles for inclusion. Data extraction and quality assessment was completed by one reviewer and verified for accuracy. Meta-analysis and indirect treatment comparison methods were used to estimate relative measures of efficacy.


Although 11 trials involving 7,127 participants were included in this review, only 2,109 (30%) and 1,738 (24%) participants contributed to the direct and indirect estimates respectively, for the primary outcome, annualized relapse rate. Oral therapy and interferon beta-1a had a significantly different rate of relapse compared to placebo (Mean difference [MD] -0.21, 95% confidence interval [CI] -0.27 to -0.16 , p < 0.00001 and MD -0.33 95% CI -0.65 to -0.01). There was a significant risk reduction of 37% and 19% in the number of patients with at least one relapse for oral therapy and interferon beta-1a compared to placebo respectively. Safety analysis favoured placebo for both sets of trials (p=0.002 and p=0.04). Indirect estimates were not significant for all three outcomes however; comparability between direct evidence was noted.


Oral pharmacotherapy and interferon beta-1a are effective compared to placebo in controlling relapse rate in patients with RRMS. The indirect measures of effect provide initial estimates of comparative efficacy and incorporation of future evidence will be necessary.

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