Rimegepant, Ubrogepant, and Lasmiditan in the Acute Treatment of Migraine Examining the Benefit-Risk Profile Using Number Needed to Treat/Harm

Abstract

Objectives: To develop and compare benefit-risk profiles for rimegepant, ubrogepant, and lasmiditan based on a network meta-analysis (NMA) of published clinical trials. Methods: A fixed-effects Bayesian NMA of randomized controlled trials of lasmiditan, rimegepant, and ubrogepant for the acute treatment of adults with migraine were used to determine risk differences for efficacy and safety outcomes of the 3 treatments compared with pooled placebo. Risk differences were used to calculate number needed to treat (NNT) for pain relief and pain freedom at 2 and 2 to 24 hours and freedom from most bothersome symptoms at 2 hours; and number needed to harm (NNH) for dizziness and nausea, relative to placebo. Results: Results were based on 5 randomized controlled trials (NCT03461757, NCT02828020, NCT02867709, NCT02439320, and NCT02605174). NNT to achieve sustained pain relief at 2 to 24 hours was lowest for rimegepant 75 mg (5; 95% credible interval [Crl]: 4, 7) and ubrogepant 100 mg (5; 95% Crl: 4, 8) and highest for ubrogepant 25 mg (8; 95% Crl: 5, 16). Rimegepant had the lowest NNT to achieve sustained pain freedom at 2 to 24 hours and lasmiditan 50 mg had the highest (7; 95% Crl: 5, 12 vs. 26; 95% Crl: 13, 95). NNH for dizziness and nausea was highest for ubrogepant 25 mg (28; 95% Crl: 15, 62 and 99; 95% Crl: −2580, 2378, respectively). Lasmiditan 200 mg had the lowest NNH for dizziness and rimegepant 75 mg had the lowest NNH for nausea. Conclusions: The benefit-risk profiles of lasmiditan, rimegepant, and ubrogepant may improve clinical decision-making.

The pharmacotherapeutic management of episodic and chronic migraine with gepants

“…Regarding freedom from MBS at 2 h post-dose, the NNTs were 15, 9, and 10 for ubrogepant 25 mg, 50 mg, and 100 mg, respectively. The NNHs to observe dizziness were 54 and −84 for ubrogepant 25 mg and 50 mg, respectively, whereas for nausea, the respective NNHs were 99, 83, and 47 for ubrogepant 25 mg, 50 mg, and 100 mg [41].…”

“…Addressing the benefit-risk profile of rimegepant 75 mg ODT in the acute treatment of migraine by using NNT and NNH, a recent meta-study demonstrated an NNT of 8 to achieve pain freedom at 2 h post-dose, an NNT of 12 to achieve freedom from MBS at 2 h post dose, and NNHs of −81 and 24 for dizziness and nausea, respectively [41]. A phase 1, open-label, single-center study enrolled healthy lactating women assessing the pharmacokinetic profile of a single 75 mg oral dose of rimegepant revealed that the estimated infant exposure to maternal rimegepant from human milk is very low.…”

A Comprehensive Review of the Mechanism, Efficacy, Safety, and Tolerability of Ubrogepant in the Treatment of Migraine

“…Ubrogepant has been compared to other treatments in terms of its efficacy in various clinical outcomes. The comparison includes other migraine medications like rimegepant and lasmiditan [ 21 , 42 ]. Regarding the accomplishment of two-hour pain freedom, ubrogepant 100 mg exhibited an odds ratio (OR) of 1.97 compared to a placebo, which is on par with rimegepant 75 mg (OR = 2.0).…”

“…However, it was less effective than lasmiditan 200 mg (OR = 2.88). When measuring the absence of MBS at two hours, ubrogepant 50 mg and 100 mg had similar ORs to lasmiditan 100 mg (OR = 1.61), lasmiditan 200 mg (OR = 1.66), and rimegepant 75 mg (OR = 1.61) [ 21 , 42 ].…”

“…For gaining relief from phonophobia at two hours, ubrogepant 50 mg and 100 mg (OR = 1.45 and 1.30, respectively) were outperformed by lasmiditan 200 mg (OR = 1.72) and rimegepant 75 mg (OR = 1.61). When looking at the freedom from nausea at two hours, ubrogepant 50 mg and 100 mg (OR = 1.24 and 1.27) were less effective than rimegepant 75 mg (OR = 1.25) and lasmiditan 200 mg (OR = 1.15) [ 21 , 42 ].…”