TREATMENT OF SECONDARY PROGRESSIVE MULTIPLE-SCLEROSIS WITH THE IMMUNOMODULATOR LINOMIDE - A DOUBLE-BLIND, PLACEBO-CONTROLLED PILOT-STUDY WITH MONTHLY MAGNETIC-RESONANCE-IMAGING EVALUATION

Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that increases the natural killer cell activity. We previously demonstrate d that linomide effectively inhibited the clinical and histopathologic signs of acute and chronic relapsing experimental autoimmune encephal omyelitis. We report a double-blind, placebo-controlled study to evalu ate tolerability and to obtain preliminary indications of the clinical efficacy of linomide on secondary progressive MS. Thirty patients suf fering from clinically definite and laboratory-supported secondary pro gressive MS, with an expanded disability status scale (EDSS) of 3.0 to 7.0, were included in this study. Patients were treated daily with li nomide (2.5 mg) or placebo orally and were followed up for side effect s and changes in their neurologic status; monthly MRI scans were taken throughout the treatment period. Twenty-four patients completed at le ast 6 months of treatment. Mild to moderate side effects, including mu scle pains, arthralgia, and edema, were present in 11 of the 15 patien ts receiving placebo and in 13 of the 15 patients treated with linomid e. At 24 weeks, the mean shift in EDSS was +0.272 +/- 0.156 in the pla cebo group versus -0.166 +/- 0.167 in the linomide group (p = 0.0451). The percentage of patients with evidence of ''activity'' on their MRI (new, enlarging, or new gadolinium diethylenetriaminepentaacetic acid [Gd-DTPA]-enhancing lesions) throughout the treatment period was 75% in the placebo group and 33% in the linomide group (p = 0.0205). The m ean total number of ew Gd-DTPA-enhancing lesions per MRI scan for the same period was 0.42 +/- 0.143 in the placebo group and 0.19 +/- 0.114 in the linomide group (p = 0.0387). In this study, linomide proved to be safe and well tolerated in patients with secondary progressive MS. In addition, our results indicate that linomide tends to inhibit the progression of the disease, especially preventing the appearance of ne w active lesions in the MRI scans. Based on these results, two multice nter phase III trials are currently under way in the United States and in Europe and Australia.