Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months. The long-term safety and durability of the effect of erenumab require further study. (Funded by Amgen and Novartis; STRIVE ClinicalTrials.gov number, NCT02456740 .).

LEV monotherapy was not superior to standard AEDs for the global outcome, namely time to treatment withdrawal, in patients with newly diagnosed focal or generalised seizures.

Background We evaluated the effect of erenumab, a fully human monoclonal antibody that inhibits the canonical calcitonin gene-related peptide receptor, on migraine-related disability, impact, and health-related quality of life among patients with episodic migraine. Methods Patients enrolled in a phase 3, 6-month, double-blind, placebo-controlled study of once-monthly erenumab 70 and 140 mg for migraine prevention (STRIVE) used an eDiary during the baseline and double-blind treatment phases to complete validated, specific questionnaires, including the modified (monthly) Migraine Disability Assessment Questionnaire; Headache Impact Test; and Migraine-Specific Quality of Life Questionnaire-role function-restrictive (MSQ-RFR), -role function-preventive (MSQ-RFP), and -emotional function (MSQ-EF). Results A total of 955 patients were randomized to receive erenumab 70 mg (n = 317), erenumab 140 mg (n = 319), or placebo (n = 319). Erenumab versus placebo resulted in significantly greater improvements in all patient-reported outcomes; changes from baseline were numerically higher with 140 mg erenumab. Improvements occurred rapidly and were maintained over 6 months of treatment. Between-group differences from placebo over months 4-6 for the 70- and 140-mg dose groups were, respectively, -2.1 and -2.8 for modified (monthly) Migraine Disability Assessment Questionnaire, -2.1 and -2.3 for Headache Impact Test, 5.1 and 6.5 for MSQ-RFR, 4.2 and 5.4 for MSQ-RFP, and 5.2 and 6.7 for MSQ-EF ( p < 0.001 for all). Erenumab also significantly reduced the proportion of patients with severe and very severe migraine-related disability and increased the proportion of patients with clinically meaningful improvements in migraine-related impact and health-related quality of life. Conclusion Erenumab reduced migraine disability and impact and improved patients' health-related quality of life, reinforcing its role as a promising new therapy for migraine prevention.

Objective:To assess efficacy and tolerability of 1-year erenumab treatment in patients with episodic migraine.Methods:Patients were randomized (n=955; 1:1:1) during the 24-week double-blind treatment phase (DBTP) to monthly subcutaneous placebo, erenumab 70 or 140mg. At Week 24, 845 patients were re-randomized (1:1) to erenumab 70 or 140mg during the 28-week dose-blinded active-treatment phase (ATP). Monthly migraine days (MMD), achieving ≥50%, ≥75% and 100% reduction in MMD, and safety/tolerability were assessed.Results:Mean MMD at DBTP baseline was 8.3. At Week 52, mean changes (SE) from pre-DBTP baseline/Week 24 (pre-ATP baseline) in MMD were −4.2 (0.2)/−1.1 (0.2) (70mg) and −4.6 (0.2)/−1.8 (0.2) (140mg) irrespective of treatment during the DBTP. For patients reducing dose from 140 (DBTP) to 70mg (ATP), change in MMD from Week 24 to 52 was −0.1 (0.3), and for those increasing from 70 (DBTP) to 140mg (ATP) was −1.8 (0.3). At Week 52, 61.0%, 38.5% and 19.8% of patients on erenumab 70mg, and 64.9%, 40.8% and 21.2% on erenumab 140mg, achieved ≥50%, ≥75% and 100% reduction in MMD from DBTP baseline, respectively. Among erenumab-treated patients in DBTP who showed ≥50% reduction in MMD during the last 3 months of DBTP and completed ATP, 86% showed sustained responses at ≥50% during the last 3 months of ATP. Safety of erenumab in the ATP was similar to the DBTP; exposure-adjusted incidence rates of adverse events were similar for either dose.Conclusion:Over 52 weeks, erenumab provided sustained efficacy in episodic migraine; the safety profiles were similar between erenumab dose groups in the presence of dose blinding.Clinicaltrials.gov identifier:NCT02456740Classification of evidence:Class II evidence that 52 weeks of treatment with erenumab 70 and 140mg subcutaneously monthly results in sustained reductions in monthly migraine days and similar dose tolerability for patients with episodic migraine.

We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions-Improvement (CGI-I) assessments of "much/very much improved" (CGI-I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (+/-SE) in IRLS score were 5.7 (+/-0.9) for placebo (median dose 0.47 mg/day) and 12.3 (+/-0.6) for pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI-I responder rates were 32.5% (placebo) and 62.9% (pramipexole) (P < 0.0001). For all secondary endpoints, pramipexole showed superior results. Pramipexole was well tolerated throughout the study.