No safety transmission was observed for ophthalmic AEs, which were monitored due to unconfirmed preclinical findings in monkeys
No safety transmission was observed for ophthalmic AEs, which were monitored due to unconfirmed preclinical findings in monkeys. 1,890 patients enrolled, 551 and 559 patients with CM received quarterly and monthly dosing; 394 and 386 patients with EM received quarterly Withaferin A HK2 or monthly, respectively. The most commonly reported AEs were injection-site reactions (induration 33%, pain 31%, and erythema 26%). Fremanezumab reduced monthly migraine days (CM quarterly ?7.2 days, CM monthly ?8.0 days, EM quarterly ?5.2 days, EM monthly ?5.1 days) and headache days of at least moderate severity (CM quarterly ?6.4 days, CM monthly ?6.8 days, EM quarterly ?4.4, EM month to month Withaferin A ?4.2 days) from baseline to 12 months. Reductions in any acute headache medication use and headache-related disability were also Withaferin A managed over 12 months. Conclusions Fremanezumab quarterly and fremanezumab monthly were well tolerated and exhibited sustained improvements in monthly migraine days, headache days, and headache-related disability for up to 12 months in patients with migraine. ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT02638103″,”term_id”:”NCT02638103″NCT02638103. Classification of evidence This study provides Class IV evidence that long-term fremanezumab treatment is usually safe, well tolerated, and effective at sustaining reductions in monthly migraine and headache days. Oral medications currently utilized for migraine preventive treatment were not originally developed to target migraine pathophysiology.1,2 They are often associated with significant side effects, leading to discontinuation and poor treatment outcomes.3,4 Observational studies have shown that persistence varies widely, ranging from as low as 19% to 79% at 6 months and from 7% to 55% at 12 months.4 Switching or reinitiating treatment after initial discontinuation of an oral migraine preventive medication prospects to even reduce persistence rates.5 Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway are a new class of preventive therapy that specifically target the pathophysiology of migraine.6,C8 They have notable advantages over conventional oral migraine preventive medications such as not requiring dose titration, having a long half-life that enables month to month or quarterly administration, and having a favorable safety profile.1,6,9 Fremanezumab, a fully humanized monoclonal antibody (IgG2a)10 that selectively targets CGRP, is approved in the United States, the European Union, and Australia for the preventive treatment of migraine in adults. The efficacy and security of fremanezumab were exhibited in 2 pivotal 12-week phase 3 randomized, double-blind, placebo-controlled efficacy studies (HALO) in patients with chronic migraine (CM) (HALO CM) and episodic migraine (EM) (HALO EM).11,12 The long-term safety, tolerability, and efficacy of fremanezumab in adults with CM or EM from your 12-month, randomized, double-blind, parallel-group, phase 3 study are reported here. Methods Standard protocol approvals, registrations, and patient consents This clinical study (“type”:”clinical-trial”,”attrs”:”text”:”NCT02638103″,”term_id”:”NCT02638103″NCT02638103) was conducted in accordance with the International Conference on Harmonisation guidelines for Good Clinical Practice, principles of the Declaration of Helsinki, and local and national regulations. The protocol was approved by the relevant national/local health government bodies and each Indie Ethics Committee/Institutional Review Table. All participants provided written informed consent. Study design This multicenter, randomized, double-blind, parallel-group, phase 3 study consisted of a screening visit, 28-day run-in period (new patients only), 12-month double-blind treatment period, and 6.5-month follow-up period for antidrug antibody (ADA) assessment (figure 1). The study was conducted from March 2016 to December 2018 at 135 sites, including clinical research centers, academic medical centers, and neurology/headache practices in the United States, Japan, Czech Republic, Russia, Canada, Finland, Poland, Israel, and Spain. Open in a separate window Physique 1 Study design for the long-term security and efficacy study of fremanezumabThis long-term study was an extension of the Efficacy and Security of Subcutaneous Administration of Fremanezumab (TEV-48125) for the Preventive Treatment of Migraine (HALO) chronic Withaferin A migraine (CM) and episodic migraine (EM) studies that allowed an additional subset of new patients who had not previously participated in the HALO studies to directly enroll. BL = baseline; EOS = end.