Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis

Abstract

Background Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. Methods A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. Results We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120 mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. Conclusion Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention.

Efficacy and safety of monoclonal antibodies targeting CGRP in migraine prevention. GRADE tables elaborated by the ad hoc working group of the International Headache Society

“…To begin, the working group performed a systematic literature search and reviewed the scientific evidence on the efficacy, tolerability and safety of monoclonal antibodies (mAb) against calcitonin gene-related peptide (CGRP) or the CGRP-receptor for the prevention of migraine. This report differs from recent meta-analyses (2,3) by providing GRADE tables. In this publication, the corresponding GRADE tables are presented.…”

“…A network meta-analysis was done independently by another working group of IHS and was published in Cephalalgia (29). In addition, a detailed analysis of safety and tolerability of the mAb was performed and published in Cephalalgia (2). The treatments from which we created GRADE tables are recent and all relevant placebo-controlled trials were supported by industry.…”

Migraine: from pathophysiology to treatment

“…In recent years, monoclonal antibodies (mABs) against the CGRP peptide (galcanezumab, fremanezumab, eptinezumab) or its canonical receptor (erenunmab) have been widely introduced in clinical practice and treatment guidelines [161]. These treatments have persistently confirmed their efficacy in phase 3 trials [162][163][164][165][166][167][168][169][170][171][172][173][174], with convenient dosing, faster onset of efficacy and mild to moderate adverse events [175,176]. Further, real-world studies have shown improvement with mABs and worsening of migraine frequency following discontinuation, with most patients resuming treatment as soon as possible following breaks due to regulatory restrictions [177][178][179][180].…”

New migraine drugs

“…The International Headache Society deems, therefore, that the composition of the author groups will provide a presentation of the efficacy and potential side effects or safety aspects of the new drugs for the treatment of acute migraine attacks and for the prevention of migraine that is as objective as possible and can be used for clinical practice. In addition to meta-analyses of efficacy and tolerability or safety for both acute and preventive medications (1–3), some of the publications address practical aspects of use, such as migraine prevention in patients with medication overuse or medication overuse headache (4), the results of open-label long-term studies for both drugs for acute therapy (5) and for migraine prophylaxis (6), and other aspects such as nonresponders to previous therapies, combination therapy switching, and termination of therapy (7,8).…”