Introduction: Migraine prophylactic therapy has changed over recent years with the development and approval of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. As new therapies emerged, leading headache societies have been providing guidelines on the initiation and escalation of such therapies. However, there is a lack of robust evidence looking at the duration of successful prophylaxis and the effects of therapy discontinuation. In this narrative review we explore both the biological and clinical rationale for prophylactic therapy discontinuation to provide a basis for clinical decision-making. Methods: Three different literature search strategies were conducted for this narrative review. These include i) stopping rules in comorbidities of migraine in which overlapping preventives are prescribed, notably depression and epilepsy; ii) stopping rules of oral treatment and botox; iii) stopping rules of antibodies targeting the CGRP (receptor). Keywords were utilized in the following databases: Embase, Medline ALL, Web of Science Core collection, Cochran Central Register of Controlled Trials, and Google Scholar. Discussion: Reasons to guide decision-making in stopping prophylactic migraine therapies include adverse events, efficacy failure, drug holiday following long-term administration, and patient-specific reasons. Certain guidelines contain both positive and negative stopping rules. Following withdrawal of migraine prophylaxis, migraine burden may return to pre-treatment level, remain unchanged, or lie somewhere in-between. The current suggestion to discontinue CGRP(-receptor) targeted mAbs after 6 to 12 months is based on expert opinion, as opposed to robust scientific evidence. Current guidelines advise the clinician to assess the success of CGRP(-receptor) targeted mAbs after three months. Based on excellent tolerability data and the absence of scientific data, we propose if no other reasons apply, to stop the use of mAbs when the number of migraine days decreases to four or fewer migraine days per month. There is a higher likelihood of developing side effects with oral migraine preventatives, and so we suggest stopping these drugs according to the national guidelines if they are well tolerated. Conclusion: Translational and basic studies are warranted to investigate the long-term effects of a preventive drug after its discontinuation, starting from what is known about the biology of migraine. In addition, observational studies and, eventually, clinical trials focusing on the effect of discontinuation of migraine prophylactic therapies, are essential to substantiate evidence-based recommendations on stopping rules for both oral preventives and CGRP(-receptor) targeted therapies in migraine. Graphical Abstract: [Figure not available: see fulltext.]
|Journal||Journal of Headache and Pain|
|Publication status||Published - 16 Feb 2023|
Bibliographical noteFunding Information:
Linda Al-Hassany, Hannah S. Lyons, Deirdre M. Boucherie, Fatemeh Farham, Karol Marschollek, Dilara Onan, Umberto Pensato, Angelo Torrente, Marta Waliszewska-Prosół declare no conflict of interest. Kristin S. Lange has received travel and accommodation expenses from Acticor Biotech and TEVA GmbH, not related to the submitted work. Elisabeth Storch has received travel and accommodation expenses from TEVA GmbH, not related to the submitted work. Uwe Reuter has received consulting fees, research grants or fees for presentations from Abbie, Allegan, Amgen, Lilly, Lundbeck, Medscape, Novartis, Pfizer, StreaMedup, Teva and the German Government (BMBF). Uwe Reuter is treasurer of the European Headache Federation.
The authors wish to thank Dr M.F.M. (Maarten) Engel from the Erasmus MC Medical Library for developing and updating the search strategies.
© 2023, The Author(s).