Glatiramer acetate after mitoxantrone induction improves MRI markers of lesion volume and permanent tissue injury in MS.
BACKGROUND
Glatiramer acetate (GA) therapy following brief, low-dose induction with mitoxantrone was safe and more effective than GA alone in suppressing inflammatory disease activity, as determined by a significant reduction in gadolinium (Gd)- enhancing MRI lesions, in a 15- month, randomized, single-blind study of relapsing-remitting multiple sclerosis (RRMS) patients.


OBJECTIVE
To determine whether effects on MRI markers of disease burden and tissue damage support and extend data on the benefits of mitoxantrone induction therapy before initiation of long-term GA therapy.


METHODS
40 RRMS patients, aged 18 to 55 years, with 1-15 Gd-enhancing lesions on screening MRI and EDSS score 0-6.5 were randomized to receive GA (20 mg/d SC), starting 2 weeks after the last of 3 monthly mitoxantrone infusions (36 mg/m2 total; n = 21), or to GA alone (20 mg/d SC; n = 19), for a total of 15 months. MRIs were obtained at baseline and months 6, 9, 12, and 15.


RESULTS
At baseline, mean (+/- SD) age was 37.2 +/- 9.7 years; disease duration, 3.5 +/- 4.8 years; EDSS score, 2.3 +/- 1.1; and number of Gd-enhancing lesions, 3.75 +/- 3.95. Reductions in Gd-enhancing lesions (RR = 0.30, 95 % CI, 0.11-0.86, p = 0.0147) and relapse activity favoring mitoxantrone- GA were accompanied by significant differences in changes in T2w lesion volume (p = 0.0139), T1w hypointense lesion volume (p = 0.0303), and proportion of Gdenhancing lesions that evolved into black holes (p = 0.0023) compared with GA alone.


CONCLUSIONS
Longterm continuous GA after brief, low-dose mitoxantrone induction is safe and more effective than GA alone. A trend toward decreased clinical disease activity was accompanied by major effects on MRI measures of disease burden and severe tissue injury.
Arnold
D L
DL
NeuroRx Research, 3605 University Street, Suite 4, Montreal, Quebec Canada. doug@neurorx.com
Campagnolo
D
D
Panitch
H
H
Bar-Or
A
A
Dunn
J
J
Freedman
M S
MS
Gazda
S K
SK
Vollmer
T
T
D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D004359:Drug Therapy, Combination; D005260:Female; D005682:Gadolinium / Q000378:metabolism; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008942:Mitoxantrone / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000627:therapeutic use*; D012044:Regression Analysis; D016037:Single-Blind Method
D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D005682:Gadolinium; D008942:Mitoxantrone