Linomide in relapsing and secondary progressive MS - Part II: MRI results

Objective: To determine the safety and efficacy of roquinimex (linomide) in the management of relapsing-remitting and secondary progressive MS as moni tored by MRI. Background: Preclinical studies and several short term random ized trials of linomide suggested clinical and MRI-measured benefits with a cceptable risk for closely followed MS patients. Methods: The North America n Linomide Trial formally screened 853 individuals for relapsing or seconda ry progressive, clinically definite MS; recent disease activity or progress ion; and an Expanded Disability Status Scale score at entry of 3.0 to 6.5 i nclusive. MRI was obtained on 811 subjects at; pre-enrollment, 718 cases at enrollment, and then at three monthly intervals until the trial was premat urely terminated for unacceptable toxicity. Results: Enhancement was found on 40.2% of 718 entry scans. Statistically robust correlations were found b etween clinical demographic data and several entry MRI measures including C SF volume, a reflection of brain atrophy. Assessment of the effect of treat ment on MRI-measured disease was limited by early trial termination. Howeve r, active treatment for 3 months reduced the proportion of patients with on e or more enhancements. An exploratory analysis suggested that 2.5 mg was t he most active of three doses tested in limiting the total volume of enhanc ed tissue, the proportion of MRI-defined lesions designated as "black holes ," and by a novel MRI composite disease measure. Conclusions: The short ter m signature of the effect of linomide on MRI-measured aspects of the diseas e suggests that safer drugs of this class might be useful in the management of MS. The use of a composite index of the heterogeneous nature of the pat hology of MS as captured by MRI may have merit as an outcome measure in cli nical trials.