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ABSTRACT
Objective
In the absence of head-to-head comparisons, the objective of this study was to conduct a network meta-analysis (NMA) to indirectly compare the relative efficacy and safety of rimegepant, ubrogepant, and lasmiditan for the acute treatment of migraine.
Methods
A systematic literature review was conducted to identify randomized controlled trials (RCTs) of rimegepant, ubrogepant, and lasmiditan in adults with acute migraine. Outcomes included sustained pain freedom and -relief 2–48 hours post-dose, and adverse events. No RCTs were identified that directly compared these interventions. Therefore, a fixed-effects Bayesian NMA was conducted by identifying a connected (via comparison to placebo) network of RCTs.
Results
Five RCTs were identified as follows: rimegepant study 303 (n = 1,466), ubrogepant ACHIEVE I and II (n = 1,672 and n = 1,686, respectively), and lasmiditan SAMURAI and SPARTAN (n = 2,231 and n = 3,005, respectively). Efficacy outcomes (pain freedom and relief at 2, 24, 48 hours) tended to be highest for lasmiditan 200 mg and rimegepant followed lower doses of lasmiditan and all doses of ubrogepant. However, lasmiditan 200 mg was also associated with higher rates of adverse events, particularly somnolence and dizziness.
Conclusions
Lasmiditan, rimegepant, and ubrogepant all performed significantly better than placebo with respect to pain freedom and pain relief. Efficacy results were similar for rimegepant and lasmiditan with rimegepant having higher rates of pain freedom and relief than lower doses of lasmiditan, while somnolence and dizziness outcomes were lower for rimegepant than higher doses of lasmiditan.
Article Highlights
Systematic literature review and network meta analysis methods were used to estimate relative efficacy and safety across three novel acute treatments for migraine.
The evidence base comprised a connected network based on five placebo-controlled Phase III trials (Study 303 for rimegepant, ACHIEVE I and II for ubrogepant, and SAMURAI and SPARTIN for lasmiditan.
All treatments had superior efficacy to placebo.
Rimegepant and lasmiditan were associated with similar outcomes, although the greatest efficacy for lasmiditan was observed at higher doses, which were also associated with an increased risk of safety endpoints (specifically, somnolence and dizziness).
Declaration of interest
KJ, EP, AD, and PD are employees of Broadstreet HEOR, which received funds from Biohaven for this work. LH, AT, RC, VC, and GL are employed by and own stock/stock options in Biohaven Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewers disclosure
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.
Author contribution statement
KJ, EP, AD, PD, LH, and GL contributed significantly to the conception and design of the work, the analysis, interpretation, and drafting of the most recently submitted version. AT, RC, VC, and JM contributed significantly to the conception of the work, the interpretation, and drafting of the most recently submitted version.
All authors agreed to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
Supplementary material
Supplemental data for this article can be accessed here.
