The American Headache Society Position Statement on Integrating New Migraine Treatments Into Clinical Practice

American Headache Society

Disclosures

Headache 

In This Article

Emerging Preventive Options

While erenumab targets the CGRP receptor, 3 other mAbs (fremanezumab, galcanezumab, eptinezumab) target the CGRP ligand. These biologic agents have demonstrated efficacy, safety, and tolerability for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 randomized, placebo-controlled trials,[43,44,47–55] and they represent the first mechanism-based and disease-specific class of preventive treatment that was designed, developed, and made available for migraine since methysergide was Food and Drug Administration approved in 1962.[56] At the time of this writing, erenumab, fremanezumab, and galcanezumab are available for use in migraine prevention, and filing is expected for eptinezumab in 2019.[57] These agents can be administered every 4 weeks (fremanezumab, galcanezumab) by subcutaneous (SC) injection or every 12 weeks by SC (fremanezumab) or intravenous (IV) (eptinezumab) infusion. None of these agents requires dose titration. All may achieve rapid treatment effects over days to weeks, and are effective in patients who have failed prior preventive treatment, as well as in those on concurrent oral preventive treatments. The lack of hepatic metabolism or renal clearance avoids interactions with concomitant drugs and these biologics may be added to or used in conjunction with other oral or injectable preventive treatments for migraine. In addition, tolerability profiles are similar to placebo, with injection site reactions being the most common.[43,44,47–55] Conclusions about long-term safety will require real-world clinical experience from use in large, heterogeneous patient populations.

These biologics will almost certainly be a higher cost to health insurance plans and patients than currently available oral generic preventive drugs. Therefore, to achieve cost-effective care while ensuring access to those most appropriate for these treatments, it is important that the indications for initiating treatment with anti-CGRP mAbs are widely understood and followed closely (Table 5). Clinical judgment may result in an emerging treatment being added to 1 or more established treatments. If initiating treatment with an anti-CGRP mAb in a patient already on a preventive treatment, since the risk of drug-mAb interactions is minimal or nonexistent, it is appropriate to add the mAb to the existing regimen and make no other changes until the effectiveness of the mAb is determined. Outcomes as outlined below should be assessed and shared decision-making between patient and provider should guide decisions on the appropriate use of polytherapy or monotherapy.

CGRP small-molecule receptor antagonists are also being studied as preventive treatments for migraine, though published data are not yet available.

Measuring Response to Emerging Preventive Options

Measuring the response to anti-CGRP mAbs will be patient- and healthcare professional-dependent and will be guided by the same outcome metrics described previously for preventive treatments, with emphasis on migraine/headache days, migraine-related disability, impact, and functional impairment. Measuring outcomes for patients on mAbs and making a decision regarding continuation requires 3 months of outcome data for patients receiving monthly injections or 6 months of follow-up for a treatment designed for quarterly injection or infusion.

Based on emerging evidence, a significant proportion of patients who do not achieve at least a 50% reduction in MHDs in the 4 weeks after the first SC dose may achieve a response in the 4 weeks after a second dose. Similarly, a smaller yet significant proportion of patients will respond in 4 to 8 weeks after a third consecutive SC dose. Therefore, it is recommended that the benefits of anti-CGRP mAbs be assessed after 3 months of treatment for those administered monthly and 6 months after the start of quarterly treatments. After 3 or 6 months of treatment, clinicians and patients should reassess the benefits of mAbs and continue treatment only if treatment benefits can be documented (Table 6). Evidence of treatment benefits may be provided by at least 1 of the following:

  1. A reduction in mean monthly headache days of 50% or more relative to the pretreatment baseline (Diary documentation is recommended but not required).

  2. A clinically meaningful improvement in a validated migraine-specific patient-reported outcome measure, including but not limited to:

    • A reduction of at least 5 points or more in Migraine Disability Assessment (MIDAS) score for those whose baseline score was between 11 and 20

    • A 30% reduction in MIDAS score for those with baseline scores above 20

    • Reduction of 5 or more points on the Migraine Physical Function Impact Diary (MPFID)

    • Reduction in scores on the 6-item Headache Impact Test (HIT-6) of at least 5 points[58]

    • Other documented benefits reported by clinician and patient

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