EAN 2026 | TRIPLE study: triple combination therapy for chronic migraine
Marina Romozzi, MD, PhD(c), Agostino Gemelli University Hospital Foundation IRCCS, Rome, Italy, discusses findings from the TRIPLE study evaluating triple combination therapy for chronic migraine. She highlights significant reductions in headache frequency, migraine-related disability, and acute medication use over 52 weeks, with improved employment outcomes and no serious safety concerns, supporting further investigation of this promising treatment strategy. This interview took place at the 12th Congress of the European Academy of Neurology (EAN) in Geneva, Switzerland.
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Transcript
Chronic migraine is a highly disabling condition despite the availability of novel and advanced treatments. Right now we have data on the combination of a single anti-CGRP agent with onabotulinumtoxinA, but we don’t have data on a possible triple combination with two anti-CGRP agents and onabotulinumtoxinA. This was a prospective study conducted at the NeuroClinic in Norway, which included patients with chronic migraine that had been on a stable treatment with onabotulinumtoxinA...
Chronic migraine is a highly disabling condition despite the availability of novel and advanced treatments. Right now we have data on the combination of a single anti-CGRP agent with onabotulinumtoxinA, but we don’t have data on a possible triple combination with two anti-CGRP agents and onabotulinumtoxinA. This was a prospective study conducted at the NeuroClinic in Norway, which included patients with chronic migraine that had been on a stable treatment with onabotulinumtoxinA. Then they added fremanezumab for at least 3 months and, for partial effectiveness, they added atogepant 60 mg daily. They were then followed up with this triple combination for 52 weeks. We included 14 patients with chronic migraine, half of them with also comorbid anxiety or depression, with a high burden due to migraine, with an average of 24 monthly headache days at baseline. Throughout the 52 weeks of treatment with the triple combination strategy, there was a significant reduction of monthly headache days and monthly migraine days, but also in other important outcome measures. So we had a reduction in the number of acute drugs and also in disability scores. It is very compelling that at the beginning of the triple combination only 20% of the patients were working full-time, and at the end 70% of the patients were working and were fully employed. Regarding safety and tolerability, we did not record any serious adverse events nor discontinuation of the three treatments, and the most frequent adverse event was constipation. That affected 14% of the cohort, but this is in line with what we see with a single anti-CGRP agent. So, in highly selected patients, the triple combination of a gepant, monoclonal antibodies targeting CGRP, and onabotulinumtoxinA can be effective and also safe. Of course, we need more data, but the rationale behind that is pretty solid because these three drugs act on different nodes in the trigeminovascular system.
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