ORLANDO, Fla. — The calcitonin gene-related peptide (CGRP) monoclonal antibody fremanezumab appears to reduce the risk for weather-related attacks in some patients with episodic migraine.

Results of a post hoc analysis of pooled data from two clinical trials showed that patients treated with fremanezumab were less susceptible to headache onset during weather patterns previously associated with increased migraine risk.

“This is actually the very first study to show that any preventive drug can help weather-associated headache,” co-author Vincent Martin, MD, told Medscape Medical News.

The findings were presented on June 6 at the American Headache Society (AHS) Annual Meeting 2026.

Weather as a Migraine Trigger

A growing body of evidence suggests barometric pressure, temperature, humidity, and other weather variables may play a role in triggering migraine attacks.

However, past analyses have primarily focused on a single weather variable at a time, said Martin, professor of clinical medicine and director of the Headache and Facial Pain Center at the University of Cincinnati Gardner Neuroscience Institute in Cincinnati.

Assessing just one weather factor “doesn’t really reflect these frontal passages because they’re a confluence of multiple weather factors together,” he added.

The HALO EM study was a 12-week multicenter, double-blind, placebo-controlled phase 3 study that assessed the efficacy of fremanezumab in 1130 participants aged 18-70. 

The HALO LTS study was a long-term safety study that involved 1890 participants (including those who completed the HALO EM study as well as new patients with episodic migraine) who took fremanezumab for 12 months.

In a post hoc analysis of the HALO EM and HALO LTS studies, Martin and colleagues found that at least 6 months of treatment with fremanezumab attenuated the association between temperature and headache days.

In the current analysis, the researchers examined 12,616 daily diary entries from 88 participants to determine whether combinations of weather variables were associated with headache onset and, if so, whether fremanezumab modified those associations.

Study participants were predominantly White (84%), female (86%), with an average age of 43 years, and 27% were concomitantly using preventive medication for migraine.

The authors used a machine-learning approach to identify 3-day weather patterns based on barometric pressure, temperature, humidity, and precipitation.

The primary outcome was the risk for a new-onset headache day — defined as a headache day preceded by a headache-free day — occurring on day 2 of each weather pattern during baseline, placebo treatment, and months 1, 3, and 6-15 of fremanezumab treatment.

Researchers adjusted for age, sex, race, geographic region, season, and concomitant medication use.

The machine-learning analysis identified six recurring weather patterns: a dry low-pressure winter/spring system (Pattern 1); a dry, cool fall high-pressure system (Pattern 2); an approaching warm front with precipitation (Pattern 3); a dry, cold winter high-pressure system (Pattern 4); an approaching cold front with precipitation (Pattern 5); and a summer Bermuda high-pressure system (Pattern 6).

Two Key Weather Patterns

Of the six weather patterns identified, only two — an approaching cold front with precipitation (Pattern 5) and a summer Bermuda high-pressure system (Pattern 6) — were associated with an increased risk for new-onset headache. 

The association between these weather patterns and headache onset was attenuated after at least 1 month of fremanezumab treatment and remained lower through months 6-15.

One possible explanation, Martin said, is that air pollution levels rise during Bermuda high-pressure systems because low wind speeds and stagnant summer air allow pollutants to accumulate.

The researchers then quantified the risk associated with the two weather patterns. At baseline, the risk for new-onset headache was 32% higher during an approaching cold front than during all other weather patterns, including the Bermuda high-pressure system (odds ratio [OR], 1.68; P = .04).

During the placebo period, both the approaching cold front (OR, 1.78; P  =.03) and the Bermuda high-pressure system (OR, 1.51; P = .01) were associated with a significantly higher risk for new-onset headache than the other four weather patterns.

After 1 month of fremanezumab treatment, the risk for new-onset headache declined significantly across all weather patterns, with reductions of 79% during approaching cold fronts, 51% during Bermuda high-pressure systems, and 66% during patterns 1 to 4, compared with baseline.

Despite these reductions, headache risk remained significantly higher during Bermuda high-pressure systems than during patterns 1-4 (OR, 1.46; P = .01).

Validation for Patients?

After 6 months of fremanezumab, the risk for new-onset headache days remained 79% lower compared with baseline during approaching cold fronts (OR, 0.21; 95% CI, 0.11-0.39).

The risk was 68% lower than at baseline during Bermuda systems (OR, 0.32; 95% CI, 0.24-0.42) and 67% lower than at baseline during the other four weather patterns (OR, 0.33; 95% CI, 0.27-0.40).

Martin acknowledged that because weather patterns vary by region, it remains unclear whether the findings are generalizable beyond the northeastern US, where study participants lived.

“I would anticipate that if you had a similar weather pattern to one of these in a given location, then it probably would be generalizable, but that’s a hypothesis at this point,” Martin said.

At a minimum, however, the findings help validate what many patients report about the weather’s influence on migraine attacks, he said. The results may also resonate with patients whose reports of weather-related triggers have sometimes been met with skepticism by clinicians.

Clinical Implications Unclear

These findings support reports from some patients that certain weather characteristics can trigger migraine attacks, said Jessica Ailani, MD, director of the MedStar Georgetown Headache Center and professor of clinical neurology at MedStar Georgetown University Hospital in Washington, DC.

“Patients often report that weather change can be the cause of migraine,” Ailani told Medscape Medical News. “Often it is rain/snow/wind that is a trigger. For some, heat or cold weather can be a trigger.”

The findings suggest that a 10-degree temperature increase may trigger headache in some patients and that fremanezumab may reduce the likelihood of such attacks, said Ailani, who was not part of the study. However, the limited detail provided in the abstract makes it difficult to determine how the findings might be applied in clinical practice.

She wondered, for example, whether different locations had different weather patterns linked to headache, why the trigger was only seen specifically with a 10-degree increase in temperature, and whether changes in barometric pressure and other temperature ranges were evaluated alongside rain and snow when assessing headache risk.

“There is a lot missing here, but I look forward to reading the full manuscript to learn more and understand how this may apply to patient care,” Ailani said. “At this time, the study is too small for a large message — just that if a patient you see has migraine and is concerned that the weather may be problematic for them, prevention may be able to help.”

The research was funded by Teva Branded Pharmaceutical Products R&D Inc. Vij reported receiving speaker fees from AbbVie, Amgen, and Biohaven Pharmaceuticals, and Martin reported receiving consulting and speaking fees as well as research support from AbbVie, Eli Lilly, Pfizer, Tonix, and Teva Pharmaceuticals. Ailani reported consulting honoraria from AbbVie, Axsome, Amneal, Aspeya, Bausch, Eli Lilly, Lundbeck, Ipsen, Merz, Pfizer, Kallyope, Satsuma, TCG Labs Soleil, and Neurocrine; clinical trial funding to her institution from Ipsen, Lundbeck, Pfizer, Merz, ShiraTronics, and Salvia; and direct clinical trial funding from Mi-Helper, as well as stocks in Minded.