Selecting migraine treatments for your patient

Professor Spierings explains some key factors to keep in mind when considering an anti-CGRP treatment, and the importance of involving patients in the decision-making process.

When is preventive treatment recommended for managing migraine?

Preventive migraine treatments can reduce the frequency, severity and duration of migraine attacks, improve function and quality of life, and may help to avoid escalating use of acute treatment, which is associated with medication overuse headache^2,6.

Consider a preventive migraine treatment if migraine attacks are severe, disabling or frequent, and for patients who cannot tolerate or are nonresponsive to acute treatment².

What are the treatment options for migraine prevention?

Treatment options for migraine prevention are summarised in Table 1.

Table 1. Preventive treatments for migraine (Adapted¹)^7–15. BID, twice daily; CGRP, calcitonin gene-related peptide; IM, intramuscular; IV, intravenous; MAOIs, monoamine oxidase inhibitors; OD, once daily; SC, subcutaneous; SSRIs, selective serotonin reuptake inhibitors. ^*Intended as a brief, high-level summary of contraindications, refer to Prescribing Information for a comprehensive list of all relevant contraindications, precautions and warnings for each medicine.

How can comorbidities influence selection of a preventive treatment for migraine?

Comorbidities in patients with migraine often include anxiety, depression, sleep disturbances and chronic pain³.

Consider a preventative treatment option with known efficacy for relevant comorbid conditions, and consider avoiding treatments that might exacerbate comorbidies or interact with co-administered medications^1,2

Recommendations and considerations for migraine prevention in specific populations are summarised in Table 2^1,2.

Table 2. Recommendations for migraine prevention in specific populations^1,2,5,16,17. CGRP, calcitonin gene-related pepide; mAbs, monoclonal antibodies; MAOIs, monoamine oxidase inhibitors; NSAID, non-steroidal anti-inflammatory drug. *A decision to prescribe preventive migraine treatment for women who are pregnant should be based on individual needs and available safety data, weighing up the risks of uncontrolled migraine on pregnancy/lactation versus those of the preventive medication².

Choosing between anti-CGRP treatments

All four CGRP monoclonal antibodies (CGRP mAbs) are approved in the US for prevention of migraine in adults ^8,9,11,12, and in Europe for prophylaxis of migraine in adults who have at least 4 migraine days per month ^13–15,18 . In Europe, CGRP mAbs are recommended as a third-line option for prevention of migraine¹.

Two small molecule CGRP antagonists (gepants; atogepant and rimegepant) are approved in the US for preventive treatment of migraine in adults^7,10. The 2021 American Headache Society Consensus Statement notes treatment plans for gepants should be based on regimens used in clinical trials and tailored to each patient¹. In February 2022, rimegepant received a positive opinion from the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) for use in migraine prevention¹⁹.

The first head-to-head study of a CGRP mAb and gepant is underway (CHALLENGE-MIG^20,21), and it remains to be seen whether the results of this study will influence migraine treatment selection.

Brief details on some key considerations are provided below.

Route and frequency of treatment administration

While some patients with migraine may prefer oral treatments², treatments administered subcutaneously or intravenously require less frequent dosing¹.

Drug interactions

Gepants

Dose adjustment is required for atogepant when co-administered with strong CYP3A4 inhibitors, strong CYP3A4 inducers and organic anion transporting polypeptide (OATP) inhibitors⁷.

Avoid concomitant administration of rimegepant with strong CYP3A4 inhibitors, strong and moderate inducers of CYP3A, and inhibitors of P-glycoprotein or breast cancer resistance protein¹⁰. Rimegepant dosing should be avoided within 48 hours when concomitantly administered with moderate CYP3A4 inhibitors¹⁰.

CGRP mAbs

No formal drug–drug interaction studies have been conducted with CGRP mAbs. However, CGRP mAbs are not metabolised by liver enzymes, so are not expected to interact with drugs that are substrates for those enzymes^12–15.

Treating patients with renal or hepatic impairment

No dose adjustment is required for CGRP mAbs, atogepant or rimegepant in patients with mild or moderate renal or hepatic impairment^7–15. For patients with severe renal impairment, dose adjustment is required for atogepant, but not for rimegepant^7,10. For patients with end-stage renal disease (CrCl <30 mL/min), rimegepant should be avoided, and dose adjustment is required for atogepant. For patients with severe hepatic impairment, both atogepant and rimegepant should be avoided^7,10.

For CGRP mAbs, there is limited data available from patients with renal and hepatic impairment from clinical trials^12–15, however, and neither is expected to affect the pharmacokinetics of monoclonal antibodies¹⁴.

Warnings and precautions

Gepants

A warning/precaution for hypersensitivity reactions is listed in the prescribing information for rimegepant¹⁰, and no precautions or warnings are listed for atogepant⁷.

CGRP mAbs

Warnings/precuations for erenumab include constipation with serious complications and hypersensitivity reactions ^8,14, and new-onset or worsening of pre-existing hypertension (US only)^88,14. Components of the erenumab injection device contain dry natural rubber latex, which may cause allergic reactions in individuals sensitive to latex^8,14.

For all CGRP mAbs, there is a lack of safety data in patients with certain major cardiovascular diseases^13–15,22, and a lack of data for eptinezumab in patients with a history of neurological diseases or those with uncontrolled/untreated psychiatric conditions²².

Involving patients in the decision-making process

Preventive medications for migraine have historically been associated with low long-term adherence, due to suboptimal efficacy and poor tolerability².

Involving patients in the decision-making process may improve treatment outcomes, adherence, persistence and treatment satisfaction^3–5

A balanced discussion about the range of treatment options for migraine may include efficacy, adverse effects, long-term safety and mechanism of action⁵. Consider the patient’s preferences, circumstances and values^2,3, particularly relating to convenience, tolerability and cost², before agreeing on a treatment plan with each patient⁵. Ensure patients are aware that it can take several weeks or months for the efficacy of a preventive treatment to be determined¹, and consider appropriate timeframes for review²³.

About Professor Egilius Spierings

Professor Egilius Spierings is the medical director of The Boston Headache Institute at Boston PainCare in Waltham, Massachusetts, United States. He is a former clinical professor of neurology and craniofacial pain at Tufts University Schools of Medicine and Dental Medicine in Boston, Massachusetts, and a former associate clinical professor of neurology at Harvard Medical School.

Disclosures

Professor Spierings is a member of the speaker bureaus of Abbvie, Amgen, Biohaven Pharmaceuticals, Lundbeck, Teva Pharmaceuticals, and Eli Lilly.

Views and opinions expressed by Professor Spierings are based on his clinical knowledge and experience, and do not represent the views of EPG Health or Medthority. This content should not be taken as medical advice and is for informational purposes only. Please consult your regional clinical practice guidelines for clinical practice recommendations in your area.

Learn more about the real-world evidence on CGRP mAbs for managing migraine

Explore the long-term evidence for safety and efficacy of CGRP mAbs for migraine

References

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3. Xu X, Ji Q, Shen M. Patient Preferences and Values in Decision Making for Migraines: A Systematic Literature Review. Pain Research and Management. 2021;2021. doi:10.1155/2021/9919773.
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