TOPLINE:

A combination of onabotulinumtoxinA and atogepant was effective and well tolerated in patients with chronic migraine, particularly in those with inadequate responses to multiple therapies, including anti-calcitonin gene-related peptide monoclonal antibodies (anti‑CGRP mAbs). Nearly half of patients achieved a ≥ 50% response at 24 weeks, with no new safety signals reported.

METHODOLOGY:

• Researchers conducted 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 9 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.

TAKEAWAY:

• At 24 weeks, 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 6 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.

IN PRACTICE:

"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.

SOURCE:

This study was led by Luigi Francesco Iannone, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. It was published online on December 02, 2025, in Cephalalgia.

LIMITATIONS:

The non-randomised design of the study restricted causal inference and introduced potential selection bias. This study 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.

DISCLOSURES:

This study did not receive any financial support. Several authors declared receiving grants, honoraria, and/or personal fees for lectures or advisory boards from various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.