If the first monoclonal antibody targeting calcitonin gene-related peptide fails to adequately prevent a patient’s migraines, should they be prescribed another? This was the question argued by Professors Andrew Charles, UCLA, USA and Patricia Pozo-Rosich, Barcelona, Spain during a debate session at #MTIS2020. Professor Patricia Pozo-Rosich reasoned that we have not yet collected enough evidence on these new therapies to recommend switching, while from the other side of the ocean Professor Charles said that, from his clinical experience, all are effective but there are differences between them to support the rationale for switching. They agreed that we still have much to learn about using these medicines in practice, nonetheless they have the potential for life-changing effects for people with migraine.
Limited evidence supports switching
Professor Pozo-Rosich argued that there is an absence of evidence, from clinical trials and real-world experience to suggest any benefit can be derived from a second calcitonin gene-related peptide (CGRP) therapy following failure of the first treatment. One recent report refers to successful switching in 3 patients.1 Part of the issue may be due to a lack of precision on definition of treatment failure. Failure of a migraine preventive may be indicated by a lack of efficacy due to persistent headache, or a lack of tolerability due to unbearable side effects.
Cyclical nature of migraine impacts response
The cyclical nature of migraine may impact on the ability to accurately measure the effect of preventives on migraine frequency. The CaMEO study of 6,000 patients identified wide variability in the frequency of both episodic and chronic migraine.2 Thus, the cyclical nature of disease may give false responders and non-responders to treatment. It may be that initial non-responders need 3 to 6 months of treatment before an effect is established.
Initial non-responders to migraine preventives may need 3 to 6 months of treatment before an effect is established
Benefit of a second CGRP therapy in practice?
In counterargument, Professor Charles reasoned that switching is common and justified with other classes of medications used to treat pain and migraine including NSAIDs, triptans and beta-blockers, so why not try with these new therapies? Within the class of monoclonal antibodies (mAbs) targeting CGRP, there are now four antibodies approved with different properties that may confer different clinical responses. The CGRP mAbs vary in antibody type, CGRP target (receptor or peptide), route of administration (intravenous or subcutaneous injection), half-life (range 21 to 32 days) and approved indications (episodic or chronic migraine, cluster headache).3
Professor Charles shared his experience at the UCLA clinic in treating around 2,500 migraine patients, which indicates that clinical experiences vary between the antibodies, both for therapeutic and adverse effects. Differences in effect can be measured as migraine frequency and severity, duration of action, and tolerance.
The potential for a ‘life changing’ response with CGRP antibodies for migraine prevention is high compared with other available therapies
In discussion, the Professors agreed that there is a growing body of evidence showing that therapeutic approaches targeting CGRP have the potential to transform the clinical management of migraine.3-5 All CGRP antibodies are found to be effective and the efficacy of treatment in real life exceeds that from clinical trials in terms of reduced monthly migraine and headache days, reduced use of acute medication, and improved quality of life. The CGRP antibodies are also effective in patients who have previously failed multiple preventives. Nonetheless, much can still be learned about appropriate prescribing in practice.
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Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.
