The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis.
OBJECTIVE
To determine whether sulfasalazine is better than placebo in slowing disability progression in MS.


METHODS
In this randomized, double-blind, placebo-controlled phase III trial, 199 patients with active relapsing-remitting (n = 151) or progressive (n = 48) MS were evaluated at 3-month intervals for a minimum of 3 years (94% completed 3 years of follow-up; mean follow-up, 3.7 years). MRI studies were performed at 6-month intervals on a subset of 89 patients.


RESULTS
Sulfasalazine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability Status Scale [EDSS] score by at least 1.0 point on two consecutive 3-month visits). Sulfasalazine influenced favorably a number of secondary outcomes during the first 18 months of the trial (e.g., annualized relapse rate, proportion of relapse-free patients; progressive subgroup only: rate of EDSS progression at 1 and 2 years, median time to EDSS progression) but these positive findings were not sustained into the second half of the trial.


CONCLUSIONS
Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, at least temporarily, without providing sustained slowing of EDSS progression. Phase III MS trials should be of sufficient length to determine a meaningful impact on disease course.
Noseworthy
J H
JH
Mayo Clinic/Mayo Foundation, Rochester, MN 55905, USA.
O'Brien
P
P
Erickson
B J
BJ
Lee
D
D
Sneve
D
D
Ebers
G C
GC
Rice
G P
GP
Auty
A
A
Hader
W J
WJ
Kirk
A
A
Duquette
P
P
Carter
J
J
Francis
G
G
Metz
L
L
Shuster
E
E
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D002170:Canada; D006233:Persons with Disabilities; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008910:Minnesota; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D012008:Recurrence; D012460:Sulfasalazine / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D012460:Sulfasalazine