Safety and Efficacy of Ubrogepant for the Acute Treatment of Episodic Migraine: A Meta-Analysis of Randomized Clinical Trials

DOI: https://doi.org/10.1007/s40263-020-00715-7

Abstract-Summary The aim was to conduct a meta-analysis to systematically evaluate the efficacy and safety of ubrogepant for the treatment of episodic migraine compared with placebo in the adult population.

Inclusion criteria were (1) randomized clinical trial; (2) enrolled adult partici- pants diagnosed with episodic migraine; (3) compared ubrogepant with placebo at doses that were evaluated in phase III clinical trials; (4) enrolled more than 100 patients in each group; and (5) provided any information on primary or secondary outcomes.

Ubrogepant use was associated with a significantly higher percentage of patients with pain freedom (ubrogepant 20.8%; placebo 12.6%; relative risk [RR] 1.65, 95% confidence interval [CI] 1.38–1.98) and absence of the most bothersome migraine- associated symptoms (ubrogepant 37.3%; placebo 27.6%; RR 1.35, 95% CI 1.20–1.53) at 2 h post-dose compared with placebo.

Ubrogepant increased the rate of absence of migraine-associated symptoms at 2 h post-dose compared with placebo (photophobia: RR 1.30 [95% CI 1.18–1.44], I2 = 49%; phonophobia: RR 1.20 [95% CI 1.11–1.29]; nausea: RR 1.07 [95% CI 1.02–1.13]), and patients were more likely to function normally at 2 h post-dose compared with placebo (RR 1.30 [95% CI 1.16–1.45]).

4.1 Acute Treatment

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Subgroup analysis demonstrated that compared to placebo, ubrogepant led to greater rates of freedom from pain at 2 h with 25-mg, 50-mg, and 100-mg doses and absence of the most bothersome symptoms with 50-mg and 100-mg doses.

The use of ubrogepant as an acute treatment of episodic migraine in adults led to a greater percentage of freedom from pain and absence of the most bothersome symptoms at 2 h post-dose.

Extended: Assessing treatment-related adverse events within 30 days failed to reveal any significant difference between each treatment subgroup and the placebo group (25 mg: RR 0.94 [95% CI 0.55–1.61], p = 0.82; 50 mg: RR 1.05 [95% CI 0.74–1.48], p = 0.79; 100 mg: RR 1.38 [95% CI 0.90–2.13], p = 0.14).

Background Previous clinical trials have demonstrated CGRP receptor blockers and monoclonal antibodies that target CGRP and CGRP receptors are efficacious for the acute and preventative treatment of migraine [35].

As a novel CGRP receptor blocker, ubrogepant (MK-1602) was developed for

the acute management of migraine.

Several clinical trials have been conducted to investigate the efficacy and safety

of ubrogepant for the acute treatment of migraine [38–50].

We performed a meta-analysis to systematically evaluate the efficacy and safety of ubrogepant for the treatment of episodic migraine compared with placebo in the adult population.

Methods Search terms included the following: ubrogepant, MK-1602, migraine, and random- ized clinical trials.

Trials were considered eligible if they (1) were randomized clinical trials; (2) enrolled adult participants diagnosed with episodic migraine; (3) compared ubroge- pant with placebo at doses evaluated in phase III clinical trials; (4) enrolled more than 100 patients in each group; and (5) provided any available information on pri- mary or secondary outcomes.

As only three available trials were included, publication bias was not evaluated. The predetermined primary efficacy outcomes included pain freedom at 2 h post- dose and absence of the most bothersome migraine-associated symptoms at 2  h post-dose.

We then analyzed pain freedom at 2 h post-dose and treatment-related adverse events within 48 h across the different dosages used in each group; 25 mg, 50 mg, and 100 mg were used in our analysis.

The heterogeneity between the included studies was evaluated with I2 and p values.

Results Absence of the most bothersome symptoms at 2 h post-dose was reported by 659 of 1765 patients (37.34%) in the ubrogepant group and by 251 of 910 patients (27.58%) in the placebo group.

For treatment-related adverse events within 48 h, we found no significant differ- ence for each dosage subgroup compared with the placebo group (25 mg: RR 0.92

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4 Treatment

[95% CI 0.56–1.49], p = 0.72; 50 mg: RR 0.98 [95% CI 0.69–1.38], p = 0.89; 100 mg: RR 1.33 [95% CI 0.90–1.97], p = 0.16).

Assessing treatment-related adverse events within 30 days failed to reveal any significant difference between each treatment subgroup and the placebo group (25 mg: RR 0.94 [95% CI 0.55–1.61], p = 0.82; 50 mg: RR 1.05 [95% CI 0.74–1.48], p = 0.79; 100 mg: RR 1.38 [95% CI 0.90–2.13], p = 0.14).

Discussion A long-term study of ubrogepant (NCT02873221) has been conducted to evaluate the safety and tolerability of intermittent treatment with ubrogepant—up to eight treatments each 4 weeks for over 1 year in migraine patients who participated in the phase III trials included in our study.

A recent network meta-analysis compared the efficacy and safety of six major CGRP receptor antagonists for acute treatment of migraine and found ubrogepant was associated with less treatment efficacy compared with other gepants [51].

The use of ubrogepant was associated with higher rates of reaching efficacy end- points compared with placebo; however, freedom from pain at 2 h post-dose was reported by 20.8% of patients who received ubrogepant compared with 12.6% in the placebo group.

Conclusion In this meta-analysis, the use of ubrogepant as an acute treatment for episodic migraine in adults led to a greater percentage of freedom from pain and absence of the most bothersome symptoms at 2 h post-dose.

Short-term use of ubrogepant was not related to an increased risk of

adverse events.

Further studies are needed to evaluate the efficacy and safety of long-term use

and in patients who do not tolerate current treatments well.

Acknowledgement A machine generated summary based on the work of Yang, Yanbo; Chen, Mingjia; Sun, Yue; Gao, Bixi; Chen, Zhouqing; Wang, Zhong. 2020 in CNS Drugs.

Rimegepant orally disintegrating tablets in the acute treatment of migraine: a profile of their use