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

• Published in: Multiple sclerosis Vol. 6; no. 2; pp. 99 - 104
• Main Authors: Tan, I L, Nijeholt, G J Lycklmaà, Polman, C H, Adér, H J, Barkhof, F
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01.04.2000; Arnold
• Subjects: Adjuvants, Immunologic - adverse effects; Adjuvants, Immunologic - therapeutic use; Adolescent; Adult; Biological and medical sciences; Cardiovascular Diseases - chemically induced; Humans; Hydroxyquinolines - adverse effects; Hydroxyquinolines - therapeutic use; Magnetic Resonance Imaging; Medical sciences; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Chronic Progressive - diagnosis; Multiple Sclerosis, Chronic Progressive - drug therapy; Multiple Sclerosis, Relapsing-Remitting - diagnosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Neurology; Treatment Outcome; magnetic resonance imaging; multiple sclerosis; Linomide; Phase III trial; Human; Roquinimex; Nervous system diseases; Multiple sclerosis; Nuclear magnetic resonance imaging; Inflammatory disease; Dose activity relation; Immunomodulator; Chemotherapy; Treatment; Central nervous system disease; Medical imagery; Evolution
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/135245850000600208

Due to an unexpected increase in serious cardiovascular event in MS patient treated with Linomide, a synthetic immunomodulator, two phase-III multinational relapsing remitting (RR) and secondary progressive (SP) MS trials had to be discontinued. MRI result of 413 patient who participated for at least 3 months were analysed. Patient received placebo, 2.5 or 5 mg Linomide. Scans were performed at pre-enrolment, month 3 and termination. The number and volume of enhancing lesions (ELV), and the number of active scans were evaluated At month 3, the decrease in the number of enhancing lesions in the placebo group was I I1%, 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=0.0 1). Analysis of the ELV showed no significant difference between placebo and treatment groups. Although Linomide has unacceptable side effect, it seems to have a modest effect on MS disease activity, as measured by MRI.