Concurrent CGRP Inhibitor and OnabotulinumtoxinA Therapy Boosts Relief in Severe Chronic Migraine


For years, study participants had been suffering with migraine symptoms and had failed at least three to five therapies before enrolling in the trial.

Image ©Andrea Danti/


Calcitonin gene-related peptide (CGRP) inhibitors may help prolong the therapeutic effect of onabotulinumtoxinA (ONA), according to findings presented during a poster session at the 61st Annual Meeting of the American Headache Society, held July 11 to 14 in Philadelphia.1 The poster was presented by Heidi Yuan, BA, study coordinator in the Headache Division, Neurology, at the University of Utah in Salt Lake City. Ms Yuan is working with a team under the direction of Seniha Ozudogru, MD, who is Assistant Clinical Professor of Neurology at the university.

Both ONA and CGRP inhibitors are indicated for the treatment of chronic migraine, with CGRP inhibitors being the newest to join the migraine treatment armamentarium. Both are injectables; ONA is administered intramuscularly every 12 weeks, and the three currently available CGRP inhibitors-erenumab, fremanezumab, and galcanezumab-are given subcutaneously every 4 weeks. A fourth CGRP inhibitor, eptinezumab, which is expected to enter the market in 2020, is an intravenous infusion meant to be administered every 12 weeks.2

Among the currently available CGRP inhibitors, erenumab has a Level A recommendation for migraine prophylaxis and is recommended by the American Academy of Neurology for patients who have not had success with other preventive therapies.3,4 ONA also has a Level A recommendation for the same indication, although its effectiveness may wane within 1 to 3 weeks before the next injection.1,3

The study

“Our current research is to put in the spotlight the possibility of exploring concurrent therapies as a better way to address onabotulinumtoxinA responders who do not experience the full duration of effect,” Ms Yuan told Neurology Times. She, Dr Ozudogru, and coinvestigators conducted a retrospective qualitative analysis to gauge whether add-on CGRP inhibitor therapy could provide an improved therapeutic effect in patients receiving ONA for treatment of chronic migraine.

They identified 34 patients with chronic migraine who were receiving ONA injections at the University of Utah Headache Clinic and who also had been prescribed erenumab therapy. The study inclusion criterion was receipt of ONA therapy before and after erenumab, with patients having had at least two injection cycles prior to beginning anti-CGRP therapy. Most study participants (91%) were women with a diagnosis of intractable chronic migraine that had been refractory to a wide range of standard treatments.

“The study participants had gone through many referrals and unsuccessful treatments before arriving at the University of Utah Headache Clinic to see one of its specialists. They had been suffering for years-decades-with chronic migraine symptoms, and had tried and failed at least three to five therapies before coming to us,” said Ms Yuan. Comorbidities also were common among participants and included depression (n=11), anxiety (n=9), insomnia (n=9), chronic tension-type headache (n=4), idiopathic neuropathy or neuropathic pain (n=4), concussion (n=3), autoimmune disorders (n=3), fibromyalgia (n=2), and occipital neuralgia (n=2).

Response to ONA, as recorded in patient chart data, was examined to determine ONA’s perceived efficacy before and after administration of CGRP inhibitor therapy. Criteria examined included number of headaches while ONA provided a therapeutic effect, number of weeks for the ONA injection to wear off, and number of headaches after the injection wore off before administration of the next subsequent injection.

Erenumab appeared to boost ONA efficacy and sustained effects in a significant proportion of participants. About half (53%) reported improvement in at least one of the three criteria indicative of ONA efficacy at their first or second injection visit following initiation of erenumab therapy. These patients reported an average increase of about 2 weeks before the ONA injection wore off. Twenty-nine percent of participants reported no change in ONA efficacy following the addition of erenumab, and 18% reported greater headache burden or decreased ONA efficacy following initiation of erenumab.

When asked about cost constraints regarding concurrent use of these therapies, Ms Yuan explained that some specialists in the clinic have been looking into extending the ONA treatment cycle and that treatment cycle adjustments might be a way to provide some cost savings for some patients.

Future directions

The study is ongoing. The team plans to continue observing the clinical progress of the study participants across additional cycles of ONA and erenumab to determine whether CGRP antibodies are effective in improving and prolonging the therapeutic effect of ONA. The data may also give insight into optimal patient selection for concurrent ONA and erenumab therapy in the treatment of intractable chronic migraine. Further prospective studies are warranted.


1. Yuan H, Baggaley S, Digre, K, Ozudogru S. CGRP antibodies as adjunctive prophylactic therapy for prolonging the therapeutic effect of onabotulinumtoxinA injections among chronic migraine patients (ongoing project). Poster presented at: 61st Annual Meeting of the American Headache Society; July 11-14, 2019; Philadelphia, PA.

2. US Food and Drug Administration accepts biologics license application for eptinezumab [press release]. Bothell, WA: Alder Biopharmaceuticals; April 22, 2019. Accessed July 19, 2019.

3. American Headache Society. The American Headache Society Position Statement on Integrating New Migraine Treatments Into Clinical Practice. Headache. 2019;59:1-18.

4. Lipton RB, Silberstein S. Migraine headache: diagnosis and current and emerging preventive treatments. Prim Care Companion CNS Disord. 2018;20(suppl E1).

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