BARCELONA — Restarting an anti-CGRP monoclonal antibody (mAb) for migraine prevention after a gap in treatment often leads to a lower efficacy rate in the second treatment period, a new study suggests.
"Only around one third of patients achieved the same level of response with an anti-CGRP-mAb in a second treatment period as in the first treatment period," said study investigator Alicia Gonzalez-Martinez, MD, PhD, Hospital Universitario de La Princesa, Madrid, Spain.
However, results of a separate study suggest that in patients who stopped treatment with an anti-CGRP mAb, often because of lack of efficacy, switching to a different anti-CGRP mAb may be an appropriate treatment option.
Both studies were presented at the 17th European Headache Congress (EHC).
RE-START Study
Presenting the RE-START trial, Gonzalez-Martinez explained that anti-CGRP antibodies are an effective prophylactic treatment for chronic migraine patients with a response rate of over 50% in clinical trials, but the optimal duration of treatment with these antibodies is unknown.
European guidelines recommend an initial treatment period of 12-18 months and then to attempt discontinuation and resume treatment if migraine significantly worsens.
The prospective RE-START study assessed the effectiveness of anti-CGRP mAbs after treatment resumption in a large sample of patients with migraine who had previously had good clinical response in the initial treatment period.
Conducted at 14 headache units in Spain between 2020 and 2022, the study included 360 patients (more than 80% women; median age 49) with high-frequency episodic migraine or chronic migraine, who had tried a median of five prior preventive treatments, and who had been using an anti-CGRP antibody for at least 12 months with a good response, but who had had migraine worsening on discontinuation. The median time between treatment periods was 4 months with a follow-up in the second treatment period of 3 months.
Results showed that monthly headache days were reduced from 20 at baseline to 5 at the end of the first treatment period. Monthly headache days increased to 16 when treatment was discontinued and then decreased again to 8 after 3 months of the second treatment period.
Monthly migraine days were reduced from 13 at baseline to 4 at the end of the first treatment period. Monthly migraine days increased to 12 during discontinuation of therapy and then decreased again to 5 after 3 months of the second treatment period.
In comparison to the first treatment period, 29% of patients experienced an improvement in monthly migraine days in the second treatment period, but the rest of the population had a worsening, with 57% experiencing a mild increase (1-4) in monthly migraine days, 11% with a moderate worsening (an increase in monthly migraine days of 5-10) and 3% with a severe worsening (an increase of more than 10 monthly migraine days).
Multivariate analysis showed that patients with earlier onset of migraine, a chronic migraine diagnosis, and overuse of NSAIDs or triptan medication were at higher risk of a poorer response in the second treatment period vs the first.
Gonzalez-Martinez noted that this was a real-world study and comes with some limitations, including the fact that the decision to restart treatment was made by the treating physician, and there was a limited follow-up period (3 months) for the second treatment period. Further follow-up is necessary to compare equal treatment time periods.
Lars Edvinsson, MD, PhD, Lund University/Hospital Sweden, chair of the EHC session where the study was presented, said the investigators did a " tremendous job."
He asked Gonzalez-Martinez what she thought about the clinical recommendation to stop and take a break from these medications. She responded that more data is needed before any firm conclusions can be made.
"I think we need more data to know for sure. In Spain, we have some places where we still have this recommendation to stop treatment after 12-18 months; in other areas they do allow treatment to be continued. Based only on effectiveness, I would say I would recommend continuing without stopping, but we don't have long-term data," she said.
She added that the decision may depend on the individual patient profiles.
"If the patient was really very bad before treatment and has responded well, then I think we could continue. An intermediate situation could be to try to stop it, but as soon as the migraine starts to worsen then we could restart treatment early on."
Switching Meds a "Reasonable Approach"
In a separate study presented at EHC, research suggested that if patients fail to respond to an anti-CGRP-mAb it may be worth switching to a different medication in the same drug class.
"Our results suggest that switching treatment to a second mAb is a reasonable approach, with around one quarter to one third of patients responding to the second treatment," study investigator Alex Jaimes, MD, Fundación Jiménez Díaz University Hospital, Madrid, told Medscape Medical News.
He explained that this retrospective cohort study was conducted to analyze results seen in patients at his hospital who had switched treatment from one anti- CGRP antibody to another.
Of 937 patients treated with anti-CGRP mAbs, 174 were switched from one agent to another. Of these, 130 met the study inclusion criteria of having received at least three doses of two different mAbs. Patients were mostly females with chronic migraine. The group had a median age of 49.
They had received a median of 10 doses of either erenumab (Aimovig) (76.9% of patients), galcanezumab (Emgality) (5.4% of patients), or fremanezumab (Ajovy) (17.7% of patients).
Reasons for switching included lack of efficacy (53.8%), administrative reasons (23.1%), adverse effects (15.4%), loss of efficacy (12.3%) and ineffectiveness upon re-initiation (1.5%).
The median treatment gap was 4 months. For the second treatment, erenumab was used in 3.1% of cases, galcanezumab in 64.6%, and fremanezumab in 32.3%.
Before the second therapy was initiated, patients experienced a median of 23 headache days and 14 monthly migraine days.
Efficacy was defined as a 50% or greater reduction in monthly headache/migraine days at 3 months and 6 months with the second treatment. This was achieved in 26% of patients at 3 months and 31.8% at 6 months.
Monthly headache days decreased from 23 to 19 days at 3 months and to 17 days at 6 months.
The median decrease in migraines decreased from 14 days to 9 days in the first quarter and remained at 9 days in the second quarter.
Noting that study participants had previously failed a median of eight preventive treatments, Jaimes said a success rate of 32% was a good result.
He explained that of the three antibodies used, one (erenumab) targeted the CGRP receptor, while the other two (galcanezumab and fremanezumab) are directed against the CGRP ligand.
"In 80% of cases when we changed the antibody we changed the target, and the results suggested that the benefits were greater when switching to an antibody directed against a different target," he said.
"It is believed that blocking the CGRP receptor and blocking the CGRP ligand may have different effects in different patients," he added.
In regression analysis, other predictors of success in switching were a lower baseline headache frequency, and a shorter time of chronic migraine.
"Our results suggest that if prophylactic treatment with one CGRP mAb is not working, we could try a different mAb and, if possible, switch to one directed against a different target," Jaimes concluded.
Gonzalez-Martinez and Jaimes report no disclosures relevant to these presentations.
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