Long-term outcome after discontinuation of CGRP monoclonal antibodies therapy for migraine: A narrative review

Migraine is a prevalent and disabling neurological disorder, particularly among patients with chronic migraine. Since the introduction of calcitonin gene–related peptide (CGRP)–targeted monoclonal antibodies (mAbs), migraine prevention has undergone a major therapeutic shift, supported by robust evidence from randomized clinical trials and real-world studies. Nevertheless, many clinical guidelines and reimbursement policies recommend treatment discontinuation after a predefined duration, despite limited data regarding long-term outcomes following cessation. This narrative review synthesizes evidence from clinical trials and real-world studies on outcomes following anti-CGRP mAb discontinuation. Within approximately three months following treatment cessation, migraine burden generally increases, frequently returning to baseline levels, although therapeutic benefits may persist in a subset of patients. Emerging data from prospective, multicenter, real-world evidence suggests that extending anti-CGRP therapy to 2- or 3-years yields progressive reductions in migraine burden compared to one year of treatment. Moreover, while the frequency of relapse decreases after the third year compared with the first, the optimal therapeutic duration to prevent long-term relapse has yet to be established. Retreatment generally restores efficacy to levels comparable to those achieved during initial therapy. These findings support individualized decisions regarding treatment duration and discontinuation and highlight the need for prospective controlled studies. Mandatory treatment interruptions imposed by reimbursement policies should therefore be reconsidered.