Estimating Changes in Clinical Outcomes after Discontinuation of Anti-CGRP Targeting Therapy for Migraine Prophylaxis: A Systematic Review and Meta-analysis.

BACKGROUND AND

OBJECTIVES

Anti-calcitonin gene-related peptide (CGRP) therapies have significantly improved migraine prevention, but the long-term impact of discontinuation remains unclear. This systematic review and meta-analysis aimed to evaluate clinical outcomes following the cessation of anti-CGRP therapy.

METHODS

PubMed, Embase, and Cochrane databases were searched up to September 2024 for randomized or observational studies reporting post-discontinuation effects in patients with episodic or chronic migraine who had been preventively treated with anti-CGRP monoclonal antibodies or gepants. The primary outcome was the mean change in monthly migraine days from baseline to post-discontinuation. Secondary outcomes included acute headache medication use, the mean change in migraine frequency from active therapy to treatment cessation, and ≥ 50% responder rates. Heterogeneity was assessed with prediction intervals (PIs) for binary outcomes and I2 statistics for continuous data. Random-effects models pooled mean differences (MDs) and risk ratios (RRs), with subgroup analyses based on follow-up duration, study design, and individuals with chronic migraine.

RESULTS

Eight studies (n = 1012) evaluating anti-CGRP monoclonal antibodies interruption were included. No studies on gepant cessation were found. Monthly migraine days decreased significantly post-discontinuation compared with baseline (MD -3.78; 95% CI -4.89, -2.67; I2 = 57%; p < 0.05), with reductions of - 5.70 days at 1 month and - 3.62 days at 3 months. Patients with chronic migraine showed sustained reductions (MD - 6.54; 95% CI - 8.64, - 4.43; I2 = 68%; p < 0.05) in the days per month with migraine between cessation and pre-treatment periods. Monthly acute headache medication days declined from baseline (MD - 1.74; 95% CI - 2.84, - 0.64; I2 = 0%; p < 0.05). Monthly migraine days increased at 3 months after discontinuation compared with just before discontinuation (MD 4.43; 95% CI 2.61, 6.25; I2 = 86%; p < 0.05), with monthly acute headache drug usage rising by 3.22 days. Responder rates of ≥ 50% declined (RR 0.42; 95% CI 0.33, 0.53; PI 0.17, 1.03; p < 0.05).

CONCLUSIONS

Migraine burden worsened after discontinuation of anti-CGRP targeting therapies but remained lower than pretreatment levels. Further research is needed to explore disease-modifying potential and optimal discontinuation strategies. PROSPERO registration number CRD42024595771.