Anti-CGRP monoclonal antibodies for migraine prevention: A systematic review and likelihood to help or harm analysis

Abstract

Introduction and objective Monoclonal antibodies targeting the calcitonin gene-related peptide pathway (anti-CGRP mAbs) have shown promising efficacy in randomised clinical trials for the prevention of episodic and chronic migraine, but no head-to-head comparisons with established treatments are available. We aimed to examine absolute differences in benefit-risk ratios between anti-CGRP mAbs, topiramate and propranolol for the prevention of episodic migraine and between anti-CGRP mAbs, topiramate and onabotulinumtoxinA for the prevention of chronic migraine using a likelihood to help versus harm analysis. Methods The number of patients needed to be treated for a patient to achieve ≥ 50% reduction in migraine days (NNTB50%) was used as an effect size metric of efficacy. The number of patients needed to be treated for a patient to experience an adverse event that led to treatment discontinuation (NNTHD-AE) was used as a measure of risk. Likelihood to help versus harm values – which are the ratios of NNTH:NNTB – were calculated using data from phase 3 randomised clinical trials. Results All agents tested were more likely to be beneficial than harmful (likelihood to help versus harm > 1) with the exception of topiramate at 200 mg per day for the prevention of episodic migraine. Anti-CGRP mAbs in all tested doses had higher LHH values than propranolol or topiramate for episodic migraine and onabotulinumtoxinA or topiramate for chronic migraine prevention. Fremanezumab had the highest LHH ratio in episodic migraine and galcanezumab in chronic migraine. Conclusion This analysis showed that anti-CGRP mAbs exhibit a more favourable benefit-risk ratio than established treatments for episodic and chronic migraine. Head-to-head studies are needed to confirm these results.

Benefit–Risk Assessment of Galcanezumab Versus Placebo for the Treatment of Episodic and Chronic Migraine Using the Metrics of Number Needed to Treat and Number Needed to Harm

“…These findings predict patient satisfaction and a better adherence profile for anti-CGRP antibodies. The results we describe here are in line with the findings of Drellia et al regarding the NNT and NNH to achieve C 50% response (C 50% reduction in migraine headache days) and the resulting LHH of galcanezumab in EVOLVE-1/2 and REGAIN [33], and we build on those findings by also evaluating pooled EVOLVE-1/-2 results, CONQUER results stratified by migraine type (EM vs. CM), and pooled 3-month results from all 4 galcanezumab studies stratified by migraine type. In addition, we have included analogous calculations for the NNT values to achieve C 30% and C 75% responses, and found that the NNTs required to achieve all tested response levels Table 5 The NNTs to achieve C 30%, C 50%, and C 75% response in migraine headache days and the NNHs for DCAEs from pooled 3-month data from patients with episodic migraine (From EVOLVE-1/-2 and CONQUER) and chronic migraine (From REGAIN and CONQUER) analysis, the data analyzed in this study are limited to dichotomous outcomes.…”

“…Because there are no head-to-head comparisons with established treatments, their analysis helps to compare the absolute differences in benefit-risk ratios between drugs. Anti-CGRP antibodies at all tested doses had higher LHH values than propranolol or topiramate for EM prevention and onabotulinumtoxinA or topiramate for CM prevention [33]. These findings predict patient satisfaction and a better adherence profile for anti-CGRP antibodies.…”

“…A benefit-risk assessment of several current preventive treatments for migraine (erenumab, topiramate, onabotulinumtoxinA, and propranolol) found that each of these four drugs were more likely to help than harm migraine patients, and the benefit-risk profile for erenumab was orders of magnitude more positive [33]. Because there are no head-to-head comparisons with established treatments, their analysis helps to compare the absolute differences in benefit-risk ratios between drugs.…”

The Role of Galcanezumab in Migraine Prevention: Existing Data and Future Directions

“…Galcanezumab is the only one shown to be efficacious in cluster headache as well [43] though, its efficacy needs to be established in more randomized clinical trials. Although no head to head trials with anti-CGRP mAbs and migraine standard prophylactic treatments have been conducted so far, according to a systematic review and a likelihood to help or harm (LHH) analysis [45] anti-CGRP mAbs had higher LHH values than propranolol or topiramate for episodic migraine and onabotulinumtoxinA or topiramate for chronic migraine prevention. Noticeably, galcanezumab had the highest LHH ratio in chronic migraine.…”

Changes in Cerebral Blood Flow after Erenumab Treatment in Good and Non-Responders—A Pilot Study of Migraine Patients

“…Calcitonin gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine and anti-CGRP monoclonal antibodies (mAbs) have been developed and showed efficacy in the prevention of migraine attacks [ 1 ]. Among four already available mAbs Erenumab (Novartis/Amgen) was the first in class approved by drug agencies and the only one blocking the CGRP receptors.…”