Effect of mitoxantrone on MRI in progressive MS: results of the MIMS trial.
OBJECTIVE
To evaluate the effects of mitoxantrone (Mx) in progressive multiple sclerosis (MS) on MRI.


METHODS
A total of 194 patients with worsening relapsing-remitting or secondary progressive MS were treated with Mx 12 mg/m2 (n = 34), Mx 5 mg/m2 (n = 40), or placebo (n = 36) at 3-month intervals IV over a 2-year period. In preselected MRI centers unenhanced and Gd-enhanced MRI scans were performed at month (M) 0, 12, and 24 in a non-randomized subset of 110 patients and non-selected for MRI criteria. The primary MRI outcome measure was the total number of MRI scans with positive Gd enhancement per group.


RESULTS
Twelve mg/m2 Mx failed to reach a significant difference from placebo as measured by the primary MRI outcome at month 12 (p = 0.431) and 24 (p = 0.065). Secondary MRI outcome measures: 5 mg/m2 Mx influenced favorably the number of Gd-enhancing lesions only at month 24 (p = 0.004), but not at month 12 (p = 0.095). Twelve mg/m2 Mx reduced the number of T2-weighted lesions at month 24 (p = 0.027) and showed a positive trend at month 12 (p = 0.069), but not 5 mg/m2 Mx. The number of active MR lesions showed a strong trend toward reduction in the 12 mg/m2 Mx group only at month 24 (p = 0.054). All comparisons are vs placebo, and unadjusted for baseline incidence.


CONCLUSIONS
In the MIMS trial 12 mg/m2 Mx does not reduce the number of MRI scans with positive Gd enhancement at month 12 and 24 vs placebo. Results of secondary MRI outcome measures are suggestive of a positive impact of 12 and 5 mg/m2 Mx on some of the Gd enhanced and unenhanced MRI measures as expected from other Mx MRI studies in the past.
Krapf
H
H
Department of Neuroradiology, Eberhard-Karls-University, Tübingen, Germany. hilmar.krapf@dgn.de
Morrissey
S P
SP
Zenker
O
O
Zwingers
T
T
Gonsette
R
R
Hartung
H-P
HP
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D008942:Mitoxantrone