Methodological considerations on real-world evidence studies of monoclonal antibodies against the CGRP-pathway for migraine: a systematic review

Abstract

Background Real-world data are accumulating on the effectiveness, tolerability and safety of anti-calcitonin gene-related peptide pathway monoclonal antibodies for the preventive treatment of migraine. We performed a systematic review of the methodology of prospective, observational, clinic-based real-world evidence studies with these drugs in both episodic and chronic migraine. Methods The objectives were to evaluate the definitions and reported outcomes used, and to perform a risk of bias assessment for each of the different studies. PubMed and EMBASE were systematically queried for relevant scientific articles. Study quality assessment of the included studies was conducted using the “National Heart, Lung and Blood Institute (NHLBI) Study Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group”. Results Forty-six studies fitted the criteria for the systematic review and were included in the analysis. Ten studies (21.7%) defined a migraine day for the study, while only 5 studies defined a headache day for the study (10.9%). The most common primary endpoint/objective of the studies was change in monthly migraine days (n = 16, 34.8%), followed by responder rate (n = 15, 32.6%) and change in monthly headache days (n = 5, 10.9%). Eight studies (17.4%) did not define the primary endpoint/objective. Thirty-three studies were graded as “good” quality and 13 studies were graded as “fair”. Conclusion Our analysis shows rather significant heterogeneity and/or lack of predefined primary outcomes/objectives, definitions of outcomes measures and the use of longitudinal monitoring (e.g. headache diaries). Standardization of terminology, definitions and protocol procedures for real-world evidence studies of preventive treatments for migraine are recommended. Trial registration This study was registered with PROSPERO with ID CRD42022369366.

The Effect of Calcitonin Gene-Related Peptide Monoclonal Antibodies on Quality of Life among Migraine Patients: Pilot Study at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics

“…Our study included more women than men. These data coincide with systematic reviews according to real-world data [23,24]. In this study, one-fifth of the patients had auras.…”

“…In this study, more patients had CM than EM before using monoclonal antibodies against CGRP. Other studies also included patients with EP and CM, but there are studies of patients with CM only [ 24 ]. Also, in many studies, patients have been diagnosed with medical overuse headache.…”

Diagnosis and treatment of migraine: an analysis of the latest diagnostic and therapeutic guidelines

“…There is currently no significant evidence in the scientific literature for the combination of almotriptan with NSAIDs. [16, [25][26][27]…”

Reporting Quality and Risk of Bias Analysis of Published RCTs Assessing Anti-CGRP Monoclonal Antibodies in Migraine Prophylaxis: A Systematic Review

“…However, there is only scarce evidence concerning the critical evaluation of the methodological quality of these RCTs. There are only a few available review studies systematically assessing the methodology of real-world studies with anti-CGRP MAbs for the preventive treatment of migraine [27] or critically discussing the outcomes and endpoints in preventive migraine RCTs [28,29]. Hence, in the current study, we systematically analyzed, according to PRISMA guidelines, the reporting quality of phase II/III RCTs involving migraine patients treated with anti-CGRP MAbs using an adapted version of the 2010 CONSORT statement checklist, thus providing insight into the publicly available information regarding these trials and their potential sources of bias.…”