A collaborative team of Norwegian and Italian researchers has announced promising results for migraine prevention, saying a combination of onabotulinumtoxinA and atogepant was effective and well tolerated in patients with chronic migraine, particularly in those with multiple treatment failures, including anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs), reports Medscape.
Nearly half of the patients achieved a ≥ 50% response at 24 weeks, with no new safety signals reported, according to the findings, published in the International Headache Society journal Cephalalgia.
The scientists carried out a real-world prospective, single-centre study at a neuroclinic in Norway to evaluate the efficacy, safety, and patient-reported outcomes of onabotulinumtoxinA combined with atogepant in patients with chronic migraine over a 24-week follow-up.
In the effectiveness cohort, 82 patients with chronic migraine were included between August 2024 and March 2025: all received at least three consecutive cycles of onabotulinumtoxinA over nine months and subsequently initiated atogepant (60 mg orally) as an add-on therapy.
Co-primary outcomes were the change in monthly migraine days and the proportion of patients achieving a ≥ 50% response (a reduction in monthly migraine days) from baseline at 24 weeks.
Secondary outcomes included changes in monthly headache days, days with acute medication use, and headache-related disability measured using the six-item Headache Impact Test (HIT-6); comparisons between patients naive to and those previously exposed to anti-CGRP mAbs; patient-reported outcomes measured using the Patient’s Global Impression of Change (PGIC) scale; and safety profile.
Progress positive
At 24 weeks, they said, the mean monthly migraine days reduced by 6.5 days from baseline (P < .001), and 45.1% of patients achieved a ≥ 50% response.
Mean monthly headache days and mean days with acute medication use reduced by six days each (P < .001 for both). Headache-related disability significantly improved, with HIT-6 scores decreased by 4 points (P < .001).
Among patients naive to anti‑CGRP mAbs, mean monthly headache days and mean monthly migraine days significantly dropped by 8.20 and 7.75 days, respectively, with significant improvement seen in HIT-6 scores (P < .001 for all).
On the PGIC scale, 87.8% of patients reported their condition at least “moderately better”. Adverse events were mild to moderate and consistent with known safety profiles of each drug; no new safety signals were reported.
“Our findings contribute to the growing evidence that might support combination therapy in migraine prophylaxis, where agents with complementary mechanisms of action may offer enhanced clinical benefit, although our study does not yet confirm that dual therapy is better than monotherapy,” the authors wrote.
The study was led by Luigi Francesco Iannone, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Limitations
The non-randomised design of the study restricted causal inference and introduced potential selection bias. It also lacked a control group treated with onabotulinumtoxinA alone, which prevented direct comparisons with monotherapy.
The absence of an atogepant monotherapy arm limited the ability to determine true synergistic effects or response to atogepant alone after partial response to onabotulinumtoxinA.
Study details
Combination preventive therapy with onabotulinumtoxinA and atogepant for chronic migraine: A 24-week, prospective, real-world evaluation (SYNERGY study)
Luigi Francesco Iannone, Marina Romozzi, Christina Sunda et al.
Published in Cephalalgia on 2 December 2025
Abstract
Background
Chronic migraine (CM) is highly disabling, and many patients fail to respond to monotherapy with approved preventive treatments. OnabotulinumtoxinA (BoNTA) and atogepant act on distinct but complementary targets within the trigeminovascular system and may exert additive or synergistic effects when used together. Real-world data on their combination remain scarce.
Methods
We prospectively analysed adult patients with CM who had received at least three prior BoNTA cycles and initiated atogepant 60 mg/day for a minimum of 24 weeks as add on to BoNTA. Co-primary outcomes were changes in monthly migraine days (MMDs) and ≥50% response rate at 24 weeks. Secondary outcomes included disability, medication use, tolerability and subgroup comparisons by prior monoclonal antibodies exposure.
Results
Among 101 patients, 82 completed 24 weeks of co-treatment. Mean MMDs decreased by 6.5 days (p < 0.001) and 45.1% of patients achieved a ≥50% reduction. Acute medication days decreased by 6.0 (p < 0.001) and Headache Impact Test-6 scores improved significantly (mean change: −4.0; p < 0.001). Patient’s Global Impression of Change scores indicated moderate-to-great improvement. Anti-calcitonin gene-related peptide naïve patients experienced larger reductions in MMDs (−7.75 vs. −5.87) and disability scores compared to non-naïve patients. Multivariable analysis identified only baseline acute medication use as predictor of response. Adverse events were mild and consistent with known safety profiles for both drugs separately; no novel safety concerns emerged.
Conclusions
The addition of atogepant to BoNTA might be effective and well tolerated in real-world setting, including CM patients previously exposed to multiple preventives. Prospective controlled trials and health-economic evaluations are warranted to validate these observations and inform future clinical guidelines.
Medscape article – OnabotulinumtoxinA Plus Atogepant Shows Promise in Chronic Migraine Prevention
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