Linomide in the treatment of multiple sclerosis: MRI results from prematurely terminated phase-III trials

Due to on unexpected increase in serious cardiovascular events in MS patien ts treated with Linomide, a synthetic immunomodulator, two phase-111 multin ational relapsing remitting (RR) and secondary progressive (SP) MS trials h ad to be discontinued. MRI results of 413 patients who participated for at least 3 months were analysed. Patients received placebo, 2.5 or 5 mg Linomi de. Scans were Performed at pre-enrolment, month 3 and termination. The num ber and volume of enhancing lesions (ELV), and the number of active scans w ere evaluated. At month 3, the decrease in the number of enhancing lesions in the Placebo group was 11% compared with 15% in the 2.5 mg group (P=0.027 ) and 23% in the 5 mg group (P=0.057). Using the percentage of active scans as outcome parameter, the odds ratio for improvement between placebo and 2 .5 mg group was 1.62 (P=0.14); between placebo and 5 mg Linomide group 3.58 (P=0.003). At termination, a rebound effect was noted in the 2.5 mg group (P=0.01). Analysis of the ELV showed no significant difference between plac ebo and treatment groups. Although Linomide has unacceptable side effects, it seems to have a modest effect on MS disease activity as measured by MRI.