Evaluating the efficacy of CGRP mAbs and gepants for the preventive treatment of migraine: A systematic review and network meta-analysis of phase 3 randomised controlled trials

Abstract

Background Several novel treatments targeting the calcitonin gene-related peptide pathway have been developed for migraine. We evaluated the efficacy of these medications, including atogepant, rimegepant, erenumab, eptinezumab, fremanezumab, and galcanezumab, for the prevention of migraine via network meta-analysis. Methods Databases, including MEDLINE via PubMed, EMBASE, and Cochrane central, were systematically reviewed, and all eligible phase 3 randomised controlled trials were included. Results Nineteen studies (n = 14,584 participants) were included. Studies included episodic (n = 11) and chronic (n = 4) migraine or both (n = 4). All interventions, except for eptinzumab 30 mg, significantly reduced mean monthly migraine days compared to placebo. All medications had a higher ≥50% responder rate than placebo and results were statistically significant in those with the subcutaneous or intravenous route of administrations, but not with the oral one. All medications significantly reduced mean monthly headache days, although no data for this outcome was available for rimegepant, and mean monthly acute medication days, with no data for eptinezumab. Conclusion The results show that medications targeting calcitonin gene-related peptide were effective in preventing migraine compared to placebo. Considering limitations of single studies, different populations such as episodic and chronic migraine, and the absence of head-to-head trials, all novel treatments decreased mean monthly migraine and headache days, and showed higher 50%, 75% and 100% responder rates than placebo. Trial registration: PROSPERO registration: CRD42022310579

Galcanezumab treatment changes visual related EEG connectivity patterns in migraine patients

“…Although we had seven patients with less than 50% reduction of headache frequency, all patients except one had on average an improvement of migraine disability and headache intensity, in agreement with the efficacy of galcanezumab after 3 months of first injection (30).…”

“…four frequency bands that we considered: delta (0.5-3.5 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”

Placebo and nocebo in the treatment of migraine: How much does real world effectiveness depend on contextual effects?

“…The treatment of choice of withdrawal of acute medications in MOH is a good example of the strong influence of nocebo in this context. Many otherwise proven effective escape medications (61) or effective prophylactics (62) and behavioral interventions (63) have often failed to add value to the treatment of withdrawal, and placebo rates have decreased notably compared to other prophylaxis studies in MOH cohorts (64,65). Thus, in the presence of MOH, the nocebo effect often appeared to superimpose placebo analgesia and lowering differences between treatment groups.…”

Preventive Treatment of Migraine

“…There is now a large body of evidence from randomized trials, long-term safety studies, real-world evidence, and clinical practice experience using CGRP-targeted therapies for migraine prevention. Several treatment guidelines and consensus statements, 3,4 systematic reviews, and meta-analyses inform this area 5-9 . This article takes a practical approach to applying the science to the preventive management of migraine and presents two illustrative patient cases.…”

“…Several treatment guidelines and consensus statements, 3,4 systematic reviews, and meta-analyses inform this area. [5][6][7][8][9] This article takes a practical approach to applying the science to the preventive management of migraine and presents two illustrative patient cases.…”