New monoclonal antibodies against the calcitonin generelated peptide pathway have recently been developed for the  prevention of migraine. The aim of this study is to compare the efficacy  of monoclonal antibodies against the calcitonin generelated peptide  pathway drugs in chronic migraine through an adjusted indirect  treatment comparison, and to establish whether they can be considered  equivalent therapeutic alternatives in this pathology.
A bibliographic search of randomized clinical trials was performed in PubMed database on December 26, 2019. The inclusion criteria were phase II/III randomized clinical trials of  monoclonal antibodies against the calcitonin generelated peptide  pathway with similar population, length of follow-up and treatment  comparator. The reduction of at least 50% migraine-days/month was  selected as efficacy endpoint. Chronic migraine was defined as ≥ 15  headache days/month, of which ≥ 8 were migraine-days (event duration  ≥ 4 hours). Randomized clinical trials with different clinical chronic  migraine context and definition of disease were excluded. An indirect  treatment comparison was developed using Bucher’s method. The  equivalent therapeutic alternatives positioning guide was used for the  evaluation of potentially equivalent alternatives. Delta value (Δ,  maximum difference as clinical criterion of equivalence) was calculated  as half of absolute risk reduction obtained in a meta-analysis of  randomized clinical trials included in indirect treatment comparison.
Thirty randomized clinical trials were found: erenumab (n =  12), fremanezumab (n = 7), galcanezumab (n = 10) and eptinezumab (n = 1). Three studies were selected: one of erenumab, one of  fremanezumab and another of eptinezumab. The rest were not included  in indirect treatment comparison for non-compliance of inclusion criteria.  Results of indirect treatment comparison among different regimens of  studied drugs showed no statistically significant differences, and the  most part of 95% confidence interval was within calculated delta margins (Δ = 9.5%). No relevant safety differences among the three drugs were  found.
Indirect treatment comparison showed no statistically  significant differences in reduction of ≥ 50% migraine days/month  between erenumab, fremanezumab and eptinezumab. Probable clinical  equivalence was found between these drugs in terms of efficacy and  safety, therefore they could be considered equivalent therapeutic  alternatives in chronic migraine.

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