An analysis of extended survival in patients with amyotrophic lateral sclerosis treated with riluzole.

BACKGROUND: In an attempt to better understand and define the progression of amyotrophic lateral sclerosis (ALS), we developed a classification of 5 discrete health states that reflect patients' activities of daily living. These health states were used to determine whether patients with ALS who are treated with riluzole differed from those treated with placebo. SETTING: Clinics for patients with ALS. DESIGN: Placebo-controlled trial of riluzole treatment in 959 patients with ALS. INTERVENTIONS: Treatment with riluzole or placebo. MAIN DEPENDENT MEASURES: A Cox model was used to assess whether, from the initial randomization to the end of an 18-month follow-up, there was a difference in the times of transition into subsequent health states between patients treated with riluzole and those treated with placebo. RESULTS: Our analysis showed a significant difference in the time to transit between the riluzole and the placebo groups in less severely affected cases, ie, state 2 and state A (the milder states) of ALS. CONCLUSION: Patients receiving riluzole remained in the milder health states longer (P<.05).

The Riluzole Early Access Programme: descriptive analysis of 844 patients in France. ALS/Riluzole Study Group III.

Recent controlled trials in outpatients with amyotrophic lateral sclerosis (ALS) indicate that riluzole prolongs tracheostomy-free survival. After 12 months' treatment, riluzole 50 mg, 100 mg and 200 mg daily reduced the risk of death or tracheostomy (relative to placebo) by 24%, 34% and 31%, respectively (by 28%, 43% and 43%, respectively, after adjustment for known prognostic factors). This survival advantage (6-9 patients require treatment with riluzole to avoid 1 death/tracheostomy annually) compares favourably with that achieved therapeutically in breast cancer and coronary artery disease. Some 6000 ALS patients are currently receiving riluzole 50 mg twice daily within the Riluzole Early Access Program. In France, this programme is being implemented as an open-label multicentre trial to assess patients' functional status and quality of life. To date, 844 patients have been enrolled, and they will be followed up for 12 months on riluzole. Baseline demographic and clinical characteristics of this study population are presented here.

Comparison of ebastine to cetirizine in seasonal allergic rhinitis in adults.

BACKGROUND: Second-generation histamine H1-receptor antagonists are accepted first-line systemic therapy for seasonal allergic rhinitis. Ebastine is a new histamine H1-receptor blocker that may differ in efficacy from currently used second-generation agents. OBJECTIVE: To compare the efficacy of daily treatment with ebastine, 10 mg, ebastine, 20 mg, or cetirizine, 10 mg, for relieving symptoms of seasonal allergic rhinitis in adults. METHODS: In this multicenter, double-blind study, outpatients were randomized to one of three parallel treatment groups: ebastine, 10 mg, ebastine, 20 mg, or cetirizine, 10 mg once daily in the morning for a 2-week period. Patients were evaluated clinically according to symptoms, discomfort, and a global assessment at baseline and on days 8 and 15 of treatment. The total symptom score, defined as the sum of the total morning score on the day of evaluation and the total evening score on the preceding day, was the primary efficacy parameter. RESULTS: Ebastine, 20 mg (n = 111), ebastine, 10 mg (116), and cetirizine, 10 mg (116), were all effective for improving nasal and ocular symptoms. There was, however, a general trend towards more rapid relief of symptoms with ebastine, 20 mg, and this reached statistical significance in some efficacy parameters after the first week of treatment. In a subpopulation of 158 patients who presented with more severe symptoms, statistically significantly greater improvement was seen with ebastine, 20 mg, compared with ebastine, 10 mg, as indicated by the mean change from baseline in the total symptom score averaged over the treatment period (-13.7 +/- 4.7 vs -11.8 +/- 3.8; P =.027) and in the morning symptom score (-6.7 +/- 2.7 vs -5.7 +/- 2.2; P = .042). All three treatments were well tolerated. Dry mouth, headache, and somnolence were the most common adverse events. CONCLUSION: Ebastine (10 mg), cetirizine (10 mg), and ebastine (20 mg) administered orally once daily for 2 weeks all appear to be effective for relieving the symptoms of seasonal allergic rhinitis. Ebastine, 20 mg, may have advantages over ebastine, 10 mg, and cetirizine, 10 mg, in terms of a reduced time to achieve maximal efficacy and a superior level of efficacy in patients with more severe symptoms.

The Rilutek (riluzole) Global Early Access Programme: an open-label safety evaluation in the treatment of amyotrophic lateral sclerosis.

OBJECTIVES: This study had two main objectives: 1. To enable patients with amyotrophic lateral sclerosis (ALS) who had not participated in previous riluzole trials to receive riluzole therapy, and 2. To expand safety experience with the drug in a broad patient population. METHODS: This was a Phase IIIb multicentre, multinational, open-label, uncontrolled single treatment study of riluzole. Patients with diagnosed possible or probable ALS were administered 100 mg of riluzole/day (50 mg b.i.d.). Clinical and laboratory adverse events were recorded every month for the first 3 months and thereafter at 3-monthly intervals. RESULTS: 8383 patients from 44 countries were entered into the study; 7916 of these patients with recorded data were administered the study drug. The mean duration of riluzole treatment was 202.1 days, with a range of 1-630 days. The most frequently reported serious and non-serious adverse events were common symptoms of ALS (respiratory symptoms and dysphagia), and only 1.9% of serious adverse events were considered to be related to the study drug. CONCLUSIONS: The safety results with this broad population (over 10% of the estimated ALS population worldwide) were consistent with those previously reported from placebo-controlled trials. No increase in adverse events and no unexpected adverse events were observed.