CGRP therapies have proved more effective in clinical practice than in trials, though adverse events (AEs) and discontinuations are more common. There is potential for both rapid and delayed responses, and there appear to be additive and synergistic effects between CGRP therapies and other preventive treatments such as botulinum toxin.
These were the main conclusions drawn by Professor David Dodick, from the Mayo Clinic, Phoenix, Arizona, USA, during the Migraine Trust Lecture 2020, CGRP therapies: what I have learned since launch.
“Efficacy seems to outperform what has been seen in clinical trials, even though we are seeing a more treatment resistant population, often on multiple medications and with multiple comorbidities that would have excluded them from clinical trials,” said Professor Dodick. “Of course, we can be more flexible than in trials and are combining treatment with lifestyle modifications and other medications and interventions but it does appear that we are seeing greater efficacy in practice.”
He reported that clinicians are seeing ‘pure responders’ who respond so well to CGRP therapies that they need infrequent or even no further injections over prolonged periods, and ‘pure non-responders’ who get no benefit at all. He discussed real world data showing that 30-35% of patients discontinue therapy due to lack of response. In small case series, up to 8-12% have discontinued treatment due to AEs, compared to approximately 2.5% in clinical trials, and it it is unclear if this is related to more severely affected populations and greater prevalence of comorbidities in clinical practice.
Professor Dodick drew attention to Food and Drug Administration (FDA) label changes for erenumab since launch as a result of emerging data showing new or exacerbated hypertension, generally within the first week of treatment and after the first dose. He explained that more research is needed to find out if this is an effect related to blocking the CGRP receptor or ligands.
“We also need to learn a lot more about who’s at risk of the hypertensive response and how best to monitor for it,” he added.
In addition, Professor Dodick referred to FDA label updates for erenumab related to warnings about hypersensitivity and serious complications of constipation.
“We knew that constipation was a bit of an issue with erenumab because it occurred in up to 3% of patients in clinical trials but we didn’t quite recognise that in some patients this might be severe,” he said.
Turning to types of response, Professor Dodick explained that clinicians are seeing both rapid and delayed responses to CGRP therapies, with some patients not responding until the second or third month of treatment, together with similar cumulative benefits over time as previously seen with other preventive agents. Additive or synergistic effects are seen with CGRP therapies and other preventive agents, including botulinum toxin, and ‘wearing off’ effects of CGRP therapies are seen in patients before their next dose is due – something that Professor Dodick said he would not have expected from pharmacokinetic studies. However, he advised against stopping treatment because of ‘wearing off’ effects.
“We don’t know whether there is true tachyphylaxis or if a patient is having a bad month or two for reasons that are unclear. But I wouldn’t suggesting discontinuing any of these antibodies if patients previously had a good sustained response and they just happen to have had a bad month,” he said.
On the potential of switching, he reported that all the specialist clinicians in his own area reported successful switching of patients between CGRP therapies following an inadequate response to initial treatment.
“Overall, experience of CGRP therapies since launch shows that there appears to be a reduction in severity and frequency of migraine attacks and an improved response to acute medication, including gepants, triptans and non specific analgesics. Hopefully, there are controlled trials underway right now that will also demonstrate whether there is a reduction in intensity and duration of individual attacks,” concluded Professor Dodick.