Efficacy and safety of subcutaneous interferon ß-1a in relapsing-remitting multiple sclerosis: further outcomes from the IMPROVE study.

BACKGROUND: The IMPROVE study demonstrated that the fetal bovine serum (FBS)- and human serum albumin (HSA)-free formulation of subcutaneous (sc) interferon (IFN) beta-1a had beneficial effects on the numbers of combined unique active magnetic resonance imaging (MRI) lesions in relapsing-remitting multiple sclerosis (RRMS). Here we report additional MRI endpoints (including post hoc analyses), and clinical efficacy, safety, and immunogenicity outcomes. METHODS: Patients with active RRMS were randomized (2:1) to IFN beta-1a, 44 mcg sc three times weekly (tiw) (n=120), or placebo (n=60), for 16 weeks (double-blind phase). All patients then received IFN beta-1a, 44 mcg sc tiw, for 24 weeks (rater-blind phase). Patients underwent MRI brain scans every 4 weeks. RESULTS: Compared with placebo, there was a 68% reduction in the mean cumulative number of new gadolinium-enhancing lesions with IFN beta-1a as early as week 4 (p<0.001), and a 53% reduction in the mean cumulative number of new T2 lesions as early as week 8 (p=0.025; post hoc analyses). During the 16-week double-blind phase, the relapse rate was 0.14 (95% confidence interval [CI] 0.09-0.23) with IFN beta-1a and 0.33 (95% CI 0.22-0.52) with placebo (p=0.010). Safety outcomes were consistent with those expected with IFN-beta treatment. CONCLUSIONS: The FBS/HSA-free formulation of sc IFN beta-1a has a beneficial impact on MRI and efficacy outcomes as early as 4 weeks after treatment initiation in patients with RRMS and has a safety profile consistent with previous trials of sc IFN beta-1a.

Comparison of cinnarizine/dimenhydrinate fixed combination with the respective monotherapies for vertigo of various origins: a randomized, double-blind, active-controlled, multicentre study.

BACKGROUND AND OBJECTIVE: Vertigo may arise from dysfunction in the peripheral and/or the central vestibular system. Simultaneous activity of a medication at both sites will serve to improve the efficacy of antivertigo treatment. The aim of this study was to compare the efficacy and tolerability of a fixed combination of the peripherally acting cinnarizine (20 mg) plus the centrally acting dimenhydrinate (40 mg) with those of equally dosed monotherapies in the treatment of vertigo of various origins. METHODS: This prospective, randomized, double-blind, active-controlled, multicentre study included patients who assessed at least one vertigo symptom as being of at least medium intensity (≥2) on a 5-point visual analogue scale (VAS; ranging from 0 = not present to 4 = very strong) and who had pathological vestibulospinal movement patterns and/or nystagmus reactions. Patients were randomly assigned to receive either cinnarizine 20 mg/dimenhydrinate 40 mg as a fixed combination, cinnarizine 20 mg as monotherapy or dimenhydrinate 40 mg as monotherapy, each three times daily for 4 weeks. Patients were examined at baseline (t(0)), and after 1 week (t(1w)) and 4 weeks (t(4w)) of treatment. The primary efficacy endpoint was the decrease in mean vertigo score (MVS) at t(4w), which was calculated by averaging the total score for 12 individual vertigo symptoms, each assessed using the 5-point VAS. RESULTS: The study included 182 patients, of whom 177 were evaluable for efficacy. The mean ± SD reduction in MVS after 4 weeks of treatment with the fixed combination (-1.44 ± 0.56) was significantly greater than the reductions with each of the active treatments alone (cinnarizine -1.04 ± 0.53; dimenhydrinate -1.06 ± 0.56; p = 0.0001, both comparisons). Cinnarizine 20 mg/dimenhydrinate 40 mg as a fixed combination was associated with a significantly higher responder rate (78% of patients with MVS ≤0.5 at t(4w)) than the monotherapies. The odds ratios for MVS ≤0.5 at t(4w) in the cinnarizine or dimenhydrinate groups versus the fixed combination group were 0.345 and 0.214, respectively. The fixed combination reduced concomitant vegetative symptoms significantly more effectively than cinnarizine at both t(1w) (p < 0.05) and t(4w) (p < 0.01). Nine patients reported 15 adverse events (AEs) [three AEs for the fixed combination, six AEs each for cinnarizine and dimenhydrinate]. At t(4w) the tolerability of the treatments was rated as very good or good by almost all patients in all groups (fixed combination and dimenhydrinate 96.6% each; cinnarizine 98.3%). CONCLUSION: The fixed combination of cinnarizine 20 mg/dimenhydrinate 40 mg was an effective and well tolerated treatment for patients with vestibular vertigo of central and/or peripheral origin. The efficacy of the fixed combination exceeded that of each of the equally dosed active substances given as monotherapy, leading to higher responder rates, and showed a very good and comparable tolerability with a similar or even smaller rate of adverse events than the active substances given alone.

Rapid benefits of a new formulation of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis.

This study evaluated the efficacy of a new formulation of subcutaneous (sc) interferon (IFN)-beta1a in relapsing-remitting multiple sclerosis (RRMS). Patients (n = 180) were randomized (2 : 1) to IFN-beta1a or placebo for 16 weeks; all patients then received IFN-beta1a for 24 weeks. Monthly brain MRI was performed. At week 16, the mean number of combined unique active (CUA) lesions was lower with IFN-beta1a than with placebo (p < 0.001; 69% fewer lesions). The mean cumulative number of CUA lesions was already lower with IFN-beta1a by week 4 (post hoc analysis; p = 0.015). The new formulation of sc IFN-beta1a has rapid beneficial effects on MRI outcomes in RRMS.

Primary spinal melanoma with bilateral papilledema.

A case of primary leptomeningeal malignant melanoma localized in the cervical region in a 41-year-old woman is presented. The only clinical finding was intracranial hypertension with papilledema. A diagnosis of primary CNS melanoma was made after dermatological and ophthalmological consultations, ruled out a metastatic lesion. Primary leptomeningeal melanoma is an extremely rare spinal tumor. Its clinical presentation with signs of increased intracranial pressure but without cord symptoms is unusual. Clinical features of this case including the radiological and histologic findings are described. Diagnosis as well as management are discussed.