Disability progression in a clinical trial of relapsing-remitting multiple sclerosis: eight-year follow-up.
OBJECTIVE
To investigate the value of Expanded Disability Status Scale (EDSS) worsening sustained for at least 6 months and other parameters as predictors for disability status.


METHODS
Retrospective analysis of the Multiple Sclerosis Collaborative Research Group study data.


METHODS
The intramuscular interferon beta-1a pivotal trial was a double-blind, placebo-controlled phase 3 study.


METHODS
Patients with relapsing-remitting multiple sclerosis who received at least 2 years of treatment and completed an EDSS evaluation 8 years postrandomization.


METHODS
Thirty micrograms of intramuscular interferon beta-1a or placebo once weekly during the 2-year clinical trial.


METHODS
Positive predictive values for 6-month sustained progression during 2 years were calculated to determine the ability to predict disability status at 8 years. A multivariate logistic regression model was used to assess the relationship between predictors and EDSS milestones at follow-up.


RESULTS
Forty-five patients had sustained 6-month EDSS progression during the clinical trial and 115 did not. Progression during the trial was the strongest predictor of reaching EDSS milestones at the follow-up visit, 8 years after randomization. Other independent predictors were treatment arm assignment and baseline EDSS score.


CONCLUSIONS
In this phase 3 clinical trial of intramuscular interferon beta-1a, compared with effects of treatment, baseline EDSS score, and number of relapses during the study, worsening of 1 point or more on EDSS from baseline lasting 6 months was the strongest predictor of clinically significant disability 8 years after randomization into the clinical trial.
Rudick
Richard A
RA
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA. rudickr@ccf.org
Lee
Jar-Chi
JC
Cutter
Gary R
GR
Miller
Deborah M
DM
Bourdette
Dennis
D
Weinstock-Guttman
Bianca
B
Hyde
Robert
R
Zhang
Hao
H
You
Xiaojun
X
D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007273:Injections, Intramuscular; D016899:Interferon-beta / Q000627:therapeutic use*; D016015:Logistic Models; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D011237:Predictive Value of Tests; D016896:Treatment Outcome
D007155:Immunologic Factors; D016899:Interferon-beta