Conference Coverage

Fremanezumab fails posttraumatic headache test


 

FROM AHS 2021

A phase 2 study of the anti-calcitonin gene–related peptide (CGRP) antibody fremanezumab found no benefit of treatment in persistent posttraumatic headache. Anti-CGRP therapy had been predicted to be effective, given its history of improving other forms of headache, and preclinical studies had suggested that CGRP plays a role in late pain sensitization that can occur after mild brain injuries.

Egilius L.H. Spierings, MD, PhD, medical director of the Boston Headache Institute.

Dr. Egilius L.H. Spierings

“There was a decrease in migraine headache days of moderate or severe intensity in both groups. But the difference between fremanezumab and placebo treatment was not statistically significant, either looking at that on a monthly basis or over the total 12 weeks of treatment,” Egilius L.H. Spierings, MD, PhD, said during his presentation of the results at the American Headache Society’s 2021 annual meeting. Dr. Spierings is medical director of the Boston Headache Institute.

Disappointing findings

“That’s sad. It’s just dreadful news,” Stewart J. Tepper, MD, professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. Dr. Tepper was not involved in the study. The results suggest that CGRP mechanisms may not be relevant to persistent posttraumatic headache, but it could still play a role at onset. “We have to rethink this. Either it’s that chronic, persistent posttraumatic headache does not have a CGRP biology, or it’s that you have to get to them earlier [in the disease process],” he said.

The negative results were surprising, according to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and former president of the International Headache Society. He noted that the study was small, and the researchers were unable to conduct subgroup analyses. “Posttraumatic headaches are usually broken down into those that phenotypically look like migraine, or phenotypically look like tension-type headache. It would have been nice to know if most of them had what clinically appears to be tension-type headache, and maybe that’s why they didn’t respond. Or did most of them have a migraine phenotype, and then it would be a little more surprising that they didn’t respond,” Dr. Rapoport said in an interview.

As a result, he believes that further studies might show that fremanezumab is an effective treatment for posttraumatic headache. “I would not give up on it. I expect that a larger study with better power, and a better idea of exactly what was wrong with the patients, might end up being a positive study,” he said.

Although most posttraumatic headaches resolve within weeks or months, some can linger or become chronic for years. Pain medication is often prescribed but should not be, according to Dr. Rapoport, because it can lead to medication overuse headache that worsens the problem. “So we badly need a good temporary preventive treatment. The thought of giving our newest, most effective preventive medications, with few adverse events, is a good one. It just didn’t seem to work in this fairly small and underpowered study,” he said.

Pages

Recommended Reading

Migraine: Cardiovascular risk status does not influence safety and efficacy of ubrogepant
Migraine ICYMI
Migraine: Lasmiditan more effective when initiated at mild pain intensity
Migraine ICYMI
Real-world evidence supports benefits of erenumab for chronic migraine
Migraine ICYMI
Fremanezumab effective in patients with difficult-to-treat migraine
Migraine ICYMI
Race, ethnicity, and socioeconomics are often barriers to migraine care
Migraine ICYMI
Comparative efficacy and safety of CGRP monoclonal antibodies in migraine
Migraine ICYMI
Migraine: Erenumab reduces acute medication usage in a real-world setting
Migraine ICYMI
Medication overuse headache: Preventive treatment with or without detoxification?
Migraine ICYMI
FDA expands rimegepant indication to include migraine prevention
Migraine ICYMI
Nitroglycerine lends insight into migraine
Migraine ICYMI