Hypertension and constipation with anti-CGRP monoclonal antibodies: a systematic review and meta-analysis

Abstract

Review title: Hypertension and constipation with anti-CGRP monoclonal antibodies: a systematic review and meta-analysis Type and method of review: Meta analysis Stage of review at time of this submission: Review ongoing — the protocol has been finalised and the peer-reviewed search prepared; formal screening not yet started. Review question: In Adults with migraine, what is the effect of Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) compared with Placebo on Incidence of hypertension (new-onset or worsening) and constipation adverse events? Searches: The following sources will be searched: Europe PMC (PubMed, MEDLINE & preprints), PubMed / MEDLINE, Embase, Scopus, Web of Science Core Collection. Additional records may be imported from other databases. No date or language restrictions are applied unless otherwise stated. The search strategy underwent peer review (PRESS) before execution. Condition or domain being studied: Adults with migraine Participants / population: Adults with migraine Intervention(s), exposure(s): Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) Comparator(s) / control: Placebo Types of study to be included: Inclusion criteria: Adults with episodic or chronic migraine; Treatment with an anti-CGRP or anti-CGRP-receptor monoclonal antibody; Reports hypertension and/or constipation adverse events; Randomised controlled trials; open-label extensions or cohort studies reporting these events; Full-text article published in English. Exclusion criteria: Gepants or other small-molecule CGRP antagonists only; No adverse event data for hypertension or constipation; Reviews, editorials, letters or conference abstracts; Overlapping cohorts (the largest or most recent report is kept) Main outcome(s): Incidence of hypertension (new-onset or worsening) and constipation adverse events Data extraction (selection and coding): Two reviewers will independently screen titles/abstracts and full texts, blinded to each other’s decisions, and extract data in duplicate using a standardised, piloted form. Disagreements will be resolved by discussion or a third reviewer. Risk of bias (quality) assessment: The risk of bias of each included study will be assessed independently by two reviewers using a study-design-appropriate tool. Disagreements will be resolved by consensus. Risk of bias in the review itself will be appraised with ROBIS. Strategy for data synthesis: Results will be synthesised narratively. Where studies are sufficiently homogeneous, effect estimates will be pooled in a meta-analysis using a fixed- or random-effects model as indicated by heterogeneity (I²). The certainty of the evidence will be rated using GRADE.