Novel acute therapies in the treatment of migraine: impact of re-dosing on cost–utility outcomes

Abstract

Recently, several novel therapies have been developed for acute treatment of migraine, all of which have shown considerable efficacy benefits over placebo. 1 Novel therapies include the calcitonin gene-related peptide (CGRP) receptor antagonists rimegepant (NURTEC ODT, Biohaven) 2 and ubrogepant (UBRELVY, Allergan) 3,4 and the 5HT-receptor agonist lasmiditan (REYVOW, Eli Lilly). 5 The design of pivotal trials for these therapies include a key difference, in that the rimegpant Phase III program only allowed for a single dose of study medication, while ubrogepant and lasmiditan trials both allowed for re-dosing: for ubrogepant, 37.6% of patients received a second dose (ACHIEVE) 3 and for lasmiditan 33% of patients required re-dosing (SAMURAI and SPARTAN). 5 The Institute for Clinical and Economic Research (ICER) conducted an evidence review in acute treatment for migraine, including network meta-analysis (NMA) and economic evaluation of

Monthly migraine days, tablet utilization, and quality of life associated with Rimegepant – post hoc results from an open label safety study (BHV3000–201)

“…Additionally, the ICER review did not consider tablet burden, which is particularly relevant given that rimegepant studies only allowed a single dose, while repeat dosing of triptans and other novel acute agents may be needed to achieve a sustained benefit [ 47 – 49 ]. A recent analysis confirmed that when the re-dosing of ubrogepant and lasmiditan was taken into account, rimegepant was associated with lower cost per QALY gained than these other novel agents [ 50 ].…”

Long-term open-label and real-world studies of lasmiditan, ubrogepant, and rimegepant for the acute treatment of migraine attacks

“…An observational study using IBM® MarketScan® Early View commercial database looking at adults with a claim for lasmiditan, rimegepant or ubrogepant between 1 January 2020 and 31 August 2020 (58). Patients prescribed lasmiditan were more likely to have a history of insufficient response to a prior acute therapy compared to patients prescribed a gepant (50% vs. 40%; p < 0.05) (58). The main reason to change acute therapy was efficacy concern such as persistent or worsening migraine attacks, prolonged time to return to function, lack of two-hour pain freedom (58).…”

“…Patients prescribed lasmiditan were more likely to have a history of insufficient response to a prior acute therapy compared to patients prescribed a gepant (50% vs. 40%; p < 0.05) (58). The main reason to change acute therapy was efficacy concern such as persistent or worsening migraine attacks, prolonged time to return to function, lack of two-hour pain freedom (58). So many factors play a role in prescription decision such as the medication mechanism of action (lasmiditan: 47%, ubrogepant: 45%, rimegepant: 51%), physician comfort/familiarity (lasmiditan: 46%, ubrogepant: 49% vs rimegepant: 39%; p < 0.05), expectations of two-hour pain freedom (rimegepant: 48% vs. ubrogepant: 36%, lasmiditan: 32%; p < 0.05), expected time for return to normal function (rimegepant: 47% vs. ubrogepant: 38%, lasmiditan: 37%; p < 0.05), expected low need for redosing/use of rescue medications (rimegepant: 23% vs. ubrogepant: 14%, lasmiditan: 14%; p < 0.05), preference for dosing formulation (rimegepant: 16% vs. ubrogepant: 5%, lasmiditan: 9%; p < 0.05 – contrary to ubrogepant or lasmiditan, rimegepant was not studied to be potentially redosed within 24-hour of use (57,59).…”

“…Using the data from the same study, patients with moderate or high risk of complications/death if infected with the coronavirus were more likely to be prescribed rimegepant (2% vs. <1%), and less likely to be prescribed a triptan (41% vs. 48%) or prescription strength NSAID (20% vs. 27%) compared to patients with a low risk of coronavirus complications (60). Looking at claims from January 2020 to August 2020, 6964 patients (88.1% women with mean age of 45.0) started a new acute treatment for migraine: 4498 (64.6%) ubrogepant, 2308 (33.1%) an oral triptan, 2205 (31.7%) rimegepant, 543 (7.8%) a non-oral triptan, and 234 (3.4%) lasmiditan (58). Contraindication to triptans was a major driver of prescribing novel acute treatments; of the patients who were prescribed lasmiditan, ubrogepant, or lasmiditan, 23.4% and 53.8% had at least one cardiovascular contraindication to triptan in the prior year and in their entire pre-index insurance history (median of seven years) respectively (58).…”

“…Looking at claims from January 2020 to August 2020, 6964 patients (88.1% women with mean age of 45.0) started a new acute treatment for migraine: 4498 (64.6%) ubrogepant, 2308 (33.1%) an oral triptan, 2205 (31.7%) rimegepant, 543 (7.8%) a non-oral triptan, and 234 (3.4%) lasmiditan (58). Contraindication to triptans was a major driver of prescribing novel acute treatments; of the patients who were prescribed lasmiditan, ubrogepant, or lasmiditan, 23.4% and 53.8% had at least one cardiovascular contraindication to triptan in the prior year and in their entire pre-index insurance history (median of seven years) respectively (58).…”