BARCELONA – A new study shows that the resumption of a monoclonal anti-CGRP antibody (mAb) for migraine prevention after a treatment gap frequently leads to a lower efficacy rate in the second treatment period.
„Only about one-third of patients achieved the same response level with an anti-CGRP mAb in a second treatment period as they did in the first treatment period,“ said lead researcher Alicia Gonzalez-Martinez, MD, PhD, from Hospital Universitario de La Princesa, Madrid, Spain.
Results from a separate study suggest that for patients who discontinued treatment with an anti-CGRP mAb, often due to lack of efficacy, switching to another anti-CGRP mAb could be a suitable treatment option. Both studies were presented at the 17th European Headache Congress (EHC).
In presenting the RE-START study, Gonzalez-Martinez explained that anti-CGRP antibodies are an effective prophylactic treatment for patients with chronic migraine, achieving a response rate of over 50% in clinical trials. However, the optimal treatment duration with these antibodies is unknown.
European guidelines recommend an initial treatment duration of 12 to 18 months and then an attempt to discontinue treatment and resume if migraine significantly worsens.
The prospective RE-START study examined the efficacy of anti-CGRP mAbs after resuming treatment in a large sample of patients with migraines who had previously shown a good clinical response in the first treatment phase.
The study was conducted between 2020 and 2022 in 14 headache centers in Spain and included 360 patients (more than 80% women; average age 49 years) with high-frequency episodic migraine or chronic migraine who had tried an average of five preventive treatments before and had used an anti-CGRP antibody with good response for at least 12 months, but experienced worsening of migraine after discontinuing treatment. The mean time between treatment periods was 4 months with a follow-up time in the second treatment period of 3 months.
The results showed that monthly headache days were reduced from 20 at the start of the study to 5 at the end of the first treatment period. Monthly headache days increased to 16 after discontinuation of treatment and then decreased to 8 after 3 months of the second treatment period. Monthly migraine days were reduced from 13 at the start of the study to 4 at the end of the first treatment period. Monthly migraine days increased to 12 during the discontinuation of therapy and then decreased to 5 after 3 months of the second treatment period.
Compared to the first treatment period, 29% of patients in the second treatment period experienced an improvement in monthly migraine days, but the rest of the population experienced a deterioration. A multivariate analysis showed that patients with earlier onset of migraine, a diagnosis of chronic migraine, and excessive use of NSAIDs or triptan medications had a higher risk of a poorer response in the second treatment period than in the first.
Gonzalez-Martinez noted that the study had some limitations and emphasized the need for further follow-up to compare equal treatment periods.
Professor Lars Edvinsson, MD, PhD, from Lund University/Hospital Sweden, chair of the EHC session, praised the researchers‘ work and asked Gonzalez-Martinez for her opinion on the clinical recommendation to discontinue these medications and take a break. She responded that more data is needed before clear conclusions can be drawn.
„I think we need more data to be sure. In Spain, there are some places where we still have the recommendation to discontinue treatment after 12 to 18 months; in other areas, they allow continuation of treatment. Based only on efficacy, I would say I would recommend continuing without interruption, but we don’t have long-term data,“ she said. She added that the decision could depend on individual patient profiles.
Medication Switch „a Reasonable Approach“
In a separate study presented at the EHC, investigations suggested that switching to another medication in the same class could be worthwhile if patients do not respond to an anti-CGRP mAb.
„Our results suggest that changing treatment to a second mAb is a reasonable approach, as about a quarter to a third of patients respond to the second treatment,“ said study researcher Alex Jaimes, MD, from Fundación Jiménez Díaz University Hospital, Madrid.
He explained that this retrospective cohort study was conducted to analyze the outcomes of patients in his hospital who had switched treatment from one anti-CGRP antibody to another.
Of 937 patients treated with anti-CGRP mAbs, 174 switched from one drug to another. Of these, 130 met the inclusion criteria for the study, meaning they had received at least three doses of two different mAbs. The predominantly female group had an average age of 49 years.
The reasons for switching were lack of efficacy (53.8%), administrative reasons (23.1%), side effects (15.4%), loss of efficacy (12.3%), and lack of efficacy upon resumption (1.5%). The average treatment gap was 4 months. In the second treatment, 3.1% used Erenumab, 64.6% used Galcanezumab, and 32.3% used Fremanezumab. Before starting the second therapy, patients had an average of 23 headache days and 14 monthly migraine days.
Efficacy was defined as a reduction of monthly headache/migraine days by 50% or more after 3 and 6 months with the second treatment. This was achieved by 26% of patients after 3 months and by 31.8% after 6 months. Monthly headache days decreased from 23 to 19 days after 3 months and to 17 days after 6 months. The average reduction in migraine decreased from 14 days to 9 days in the first quarter and remained at 9 days in the second quarter.
Jaimes emphasized that the study participants had previously failed an average of eight preventive treatments, and a success rate of 32% was a good result. He explained that one of the three antibodies used targeted the CGRP receptor, while the other two targeted the CGRP ligand.
„In 80% of the cases where we switched the antibody, we also switched the target, and the results suggest that the benefits were greater when we switched to an antibody directed at a different target,“ he said. „It is believed that blocking the CGRP receptor and blocking the CGRP ligand can have different effects on different patients.“
Additional predictors of the success of the switch were a lower initial frequency of headaches and a shorter duration of chronic migraine.
„Our results suggest that if prophylactic treatment with an anti-CGRP mAb does not work, we could try another mAb and, if possible, switch to one targeted at a different target,“ Jaimes concluded.
Gonzalez-Martinez and Jaimes reported no relevant disclosures for these presentations.