Objective: Assess the effects of rimegepant on quality of life (QoL) over 1-year of open-label treatment in which rimegepant was used for both preventive and acute treatment for migraine. Background: Rimegepant is an orally administered small molecule CGRP receptor antagonist for the acute and preventive treatment of migraine. Design/Methods: This open-label extension phase of a 12-week, phase 2/3, randomized, double-blind, placebo-controlled study (NCT03732638) enrolled adults aged ≥18 years with a history of 4–18 moderate to severe monthly migraine attacks. Subjects completing 12 weeks of double-blind treatment with rimegepant 75 mg or placebo every other day could continue with open-label treatment with rimegepant 75 mg for 52 weeks of preventive treatment. On nonscheduled dosing days, subjects could take open-label rimegepant 75 mg as needed up to once per day for acute treatment of migraine. The effects of rimegepant on QoL were measured using Migraine-Specific Quality-of-Life Questionnaire v 2.1 (MSQ) scores on the role restrictive (RR), role preventative (RP), and emotional function (EF) domains. Changes from baseline in MSQ domain scores were assessed at Weeks 12 and 52 of the open-label phase (ie, overall study Weeks 24 and 64). Higher MSQ scores indicated better quality of life. Results: Respective mean (SD) baseline MSQ scores for the RR, RP, and EF domains were 51.0 (18.70), 65.2 (21.01), and 57.7 (27.23). At Week 12 (n=536) mean (SD) changes from baseline in RR, RP, and EF, respectively, were 28.4 (22.71), 21.8 (21.46), and 27.4 (26.58); at Week 52 (n=398), they were 32.9 (21.46) for RR, 25.1 (21.66) for RP, and 30.1 (26.40) for EF. Conclusions: Long-term treatment with oral rimegepant 75 mg taken every other day for preventive treatment and up to once daily on nonscheduled days as needed for acute treatment was associated with improvements in migraine-specific QoL. Disclosure: Dr. Pavlovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Turner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan, Amgen, Novartis, Teva, Lilly, Lundbeck, Biohaven,Impel. Dr. Turner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen, Teva, Allergan, Biohaven, Lilly, Lundbeck, Theranica, Revance. Dr. Turner has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Allergan, Amgen, Biohaven, Teva, Novartis, Lundbeck, Lilly. The institution of Dr. Turner has received research support from Allergan, Amgen, Biohaven, Lilly, Lundbeck, Theranica. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck . Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Allergan. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lundbeck. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for lilly. The institution of Dr. Winner has received research support from Amgen. The institution of Dr. Winner has received research support from Allergan. The institution of Dr. Winner has received research support from Lundbeck . The institution of Dr. Winner has received research support from Novartis. The institution of Dr. Winner has received research support from Lilly. The institution of Dr. Winner has received research support from Teva. The institution of Dr. Winner has received research support from Supernus. The institution of Dr. Winner has received research support from Biogen. The institution of Dr. Winner has received research support from Avinar. The institution of Dr. Winner has received research support from SAMUS. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Gilbert J. L'Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L'Italien has received stock or an ownership interest from biohaven pharmaceuticals. Dr. Jensen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Jensen has stock in Biohaven Pharmaceuticals. Alexandra Thiry has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Alexandra Thiry has received stock or an ownership interest from Biohaven Pharmaceuticals. Lisa Kamen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc.. Lisa Kamen has received stock or an ownership interest from Biohaven Pharmaceuticals, Inc.. Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.
CD4 is widely known as the HIV receptor, but is insufficient to allow viral infection. Recently, members of the family of chemokine receptors have been identified as the missing co-receptors, which act with CD4 to allow the virus to enter cells. These discoveries open up the possibilities of novel therapeutic strategies to combat HIV infection and AIDS.
Objective The objective of this study was to ascertain to what extent adults with migraine value an early onset of efficacy for preventive migraine treatments. Background In placebo-controlled clinical trials, treatment with eptinezumab resulted in a lower proportion of adults with migraine on the first day following infusion (day 1; 14% point-reduction for chronic migraine [CM] in PROMISE-2 and 8% point-reduction for episodic migraine [EM] in PROMISE-1). Methods Adults with migraine completed an online preference-elicitation thresholding exercise to ascertain to what extent they value not having a migraine on day 1 postdosing relative to a clinically relevant reduction in number of migraine days during the first month postdosing (>= 2 migraine-free days for CM and >= 1 migraine-free days for EM). Results One hundred and one participants (mean age, 50.6 +/- 12.4 years; 81 [80%] women) were included. In participants with CM, 29 of 50 (58%) considered the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing to be at least as important as a clinically relevant reduction in number of migraine days the first month postdosing, whereas 37 of 50 (74%) considered a clinically relevant reduction of migraine days the first month postdosing to have a value equivalent to the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing. In participants with EM, 18 of 35 (51%) considered the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing to be at least as important as a clinically relevant reduction in migraine days the first month postdosing, whereas 24 of 35 (69%) considered a clinically relevant reduction of migraine days the first month postdosing to have a value equivalent to the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing. Conclusion Most participants considered the reduction in the likelihood of migraine offered by eptinezumab on day 1 postdosing to be at least as important as a clinically relevant reduction in migraine days the first month postdosing.
Abstract Background Eptinezumab is an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody approved for the preventive treatment of migraine. In the phase 3 RELIEF study, eptinezumab resulted in shorter time to headache pain freedom and time to absence of most bothersome symptom (MBS; including nausea, photophobia, or phonophobia) compared with placebo when administered during a migraine attack. The objective of this exploratory analysis was to examine the earliest time points that eptinezumab separated from placebo (P < .05) on headache- and migraine-associated symptoms when administered during a migraine attack. Methods RELIEF, a multicenter, parallel-group, double-blind trial, occurred from November 7, 2019, through July 8, 2020. Adults considered candidates for preventive treatment were randomized to eptinezumab 100 mg (N = 238) or placebo (N = 242) administered intravenously over 30 min within 1–6 h of migraine onset. Outcome measures included headache pain freedom/relief and absence of MBS, patient’s choice of photophobia, phonophobia, or nausea, at regular intervals from 0.5 to 48 h after infusion start. Censoring was applied at time of acute rescue medication use. Results At hour 1, more eptinezumab-treated patients achieved headache pain freedom (9.7%), headache pain relief (38.7%), and absence of MBS (33.2%) versus placebo (4.1%, 26.9%, and 22.1%, respectively; P < .05 all), with separation from placebo (P < .05) through hour 48. Eptinezumab separated from placebo (P < .05) at hour 1 in absence-of-photophobia (29.4% vs 17.0%) and absence-of-phonophobia (41.2% vs 27.2%) and through hour 48. Initial separation from placebo (P < .05) in absence-of-nausea occurred at end-of-infusion (0.5 h; 36.7% vs 25.4%, respectively). Conclusion Preventive treatment with eptinezumab initiated during a migraine attack resulted in more patients achieving headache pain freedom/relief and absence of MBS, with separation from placebo (P < .05) as early as 0.5–1 h following the start of infusion. Rapid resolution of headache- and migraine-associated symptoms by a peripherally acting, intravenously administered antibody suggest a peripheral site of pharmacological action for CGRP blockade. Trial registration ClinicalTrials.gov Identifier: NCT04152083 .
Background A clinical ability to describe the response trajectory of patients receiving preventive migraine treatment could expedite and improve therapeutic management decisions. This post hoc analysis of the PROMISE-2 study evaluated the consistency and predictive power of Month 1 treatment response on later response in patients with chronic migraine. Methods PROMISE-2 was a double-blind, placebo-controlled trial that randomized adults with chronic migraine to eptinezumab 100 mg, 300 mg, or placebo administered IV every 12 weeks for up to 24 weeks (2 infusions over 6 study months). Migraine responder rates (MRRs) were calculated from monthly migraine days over 4-week intervals compared with baseline. Patients were grouped by MRR during Month 1 (< 25%, 25–< 50%, 50–< 75%, and ≥ 75%), with the number of subsequent study months (Months 2–6) with ≥50% and ≥ 75% MRR calculated in each subgroup. A similar analysis was conducted using Patient Global Impression of Change (PGIC) rating to define Month 1 subgroups (very much improved, much improved, minimally improved, and no change/worse) and rates of very much improved or much improved PGIC during Months 2–6. Results In the eptinezumab 100 mg, 300 mg, and placebo groups, respectively, 194/356 (54.5%), 212/350 (60.6%), and 132/366 (36.1%) patients were ≥ 50% migraine responders during Month 1. More eptinezumab-treated patients were ≥ 75% migraine responders (100 mg, 110/356 [30.9%]; 300 mg, 129/350 [36.9%]; placebo, 57/366 [15.6%]) and more placebo-treated patients were < 25% migraine responders (eptinezumab 100 mg, 103/356 [28.9%]; 300 mg, 80/350 [22.9%]; placebo, 153/366 [41.8%]). Among patients who achieved ≥75% migraine response in Month 1, more than one-third attained ≥75% migraine response for all 5 subsequent study months and more than two-thirds achieved ≥75% migraine response for ≥3 months. More than two-thirds of those in the very much improved (PGIC) subgroup at Month 1 were much or very much improved for all 5 subsequent months. Conclusions In this post hoc analysis of data from PROMISE-2, more eptinezumab-treated than placebo-treated patients were early (Month 1) responders, and most early responders went on to achieve a high level of response for at least half of the 24-week treatment period. Potential for later response in early non-responders was also observed. Trial registration ClinicalTrials.gov identifier: NCT02974153 ; registered November 23, 2016.
