Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study

Ashina, Messoud; Tepper, Stewart J.; Brandes, Jan Lewis; Reuter, Uwe; Boudreau, Guy; Doležil, David; Cheng, Sunfa; Zhang, Feng; Lenz, Robert; Klatt, Jan; Mikol, Daniel D.

doi:10.1177/0333102418788347

Cited by 130 publications

(145 citation statements)

References 11 publications

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“…Preliminary findings in erenumab‐treated patients (140 mg dose) with episodic migraine who had failed at least one previous preventive drug class demonstrated greater placebo‐adjusted treatment differences in the treatment failure subgroups versus the overall population . Similar findings were observed, with greater clinical benefits observed for the erenumab 140 mg dose amongst patients with chronic migraine after monthly erenumab injections versus placebo in patients with prior treatment failures (≥1, ≥2 and ≥3) .…”

Section: Discussionsupporting

confidence: 77%

Positive response to galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double‐blind studies

Ailani

Pearlman

Zhang

et al. 2019

Euro J of Neurology

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Background and purpose Humanized monoclonal antibody galcanezumab, which binds to calcitonin‐gene‐related peptide, has shown efficacy for episodic and chronic migraine prevention. These analyses evaluated galcanezumab response for migraine headache prevention in patients who previously failed onabotulinumtoxinA (‘nonresponse’ or ‘inadequate response’ or safety reasons). Methods Post hoc analyses included data from three double‐blind, placebo‐controlled, phase 3 episodic or chronic migraine studies; 2886 patients randomly received 120 or 240 mg galcanezumab or placebo. During double‐blind periods the study drug was administered subcutaneously once a month for 6 months in EVOLVE‐1 and ‐2 and for 3 months in REGAIN. The 120 mg groups received a 240 mg loading dose at month 1. Pooled analyses included 129 patients who failed onabotulinumtoxinA. Using mixed effect model repeat measurements, the least squares mean change from baseline in the number of migraine headache days (MHDs) was calculated for the first 3 months of treatment. Results For pooled analyses, significant decreases from baseline in the number of MHDs were observed for 120 mg (−3.91) and 240 mg (−5.27) galcanezumab overall versus placebo (−0.88) across 3‐month time points for patients who failed onabotulinumtoxinA. Corresponding data for patients with chronic migraine showed significant decreases: 120 mg (−3.18) and 240 mg (−4.26) galcanezumab versus placebo (0.16). Significant reductions in the number of MHDs per month with acute medication use included 120 mg galcanezumab (−4.35) and 240 mg galcanezumab (−4.55) versus placebo (−0.83). Estimates of ≥50% response during months 1–3 were 9.4% for placebo, 41.3% for 120 mg galcanezumab and 47.5% for 240 mg galcanezumab. Conclusion Galcanezumab is an option for prevention of migraine in patients who have previously failed onabotulinumtoxinA preventive therapy.

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Section: Discussionsupporting

confidence: 77%

Positive response to galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double‐blind studies

Ailani

Pearlman

Zhang

et al. 2019

Euro J of Neurology

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“…Significantly more erenumab, than placebo‐treated subjects, achieved ≥50% reduction in MMD (30% vs 14%). In CM subjects who failed 0 vs >1 preventive (n = 214 vs 327) erenumab achieved a change in MMD of 6.1 vs 7.0 (140 mg), 7.9 vs 5.4 (70 mg) and 5.7 vs 2.7 (placebo) days . A higher erenumab dosage seemed to work better in CM subjects who have failed previous preventives.…”

Section: Cgrp Function‐blocking Therapy In Migraine and Cluster Headachementioning

confidence: 93%

Targeting CGRP for the Prevention of Migraine and Cluster Headache: A Narrative Review

2019

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Calcitonin‐gene‐related peptide (CGRP), a neuropeptide broadly distributed in neuronal and non‐neuronal regions throughout the body, plays a fundamental role in migraine and cluster headache (CH) pathophysiology. CGRP functional blockade alleviates neurogenic inflammation and reduces pain pathway sensitization. Two types of CGRP function‐blocking modalities, monoclonal antibodies (MAbs), and small molecules (gepants), have been designed to target the CGRP ligands and CGRP receptors. In this narrative review, we summarized the latest clinical trials on gepants and CGRP function‐blocking MAbs for migraine and CH prevention. At the time of writing, newer gepants are currently under Federal Drug Administration (FDA) review for migraine management, but there is no study yet on the usage of gepants for CH. Erenumab, fremanezumab, and galcanezumab have been approved by the FDA for migraine prevention while eptinezumab is under FDA review. CGRP MAbs are as effective as and more tolerable than conventional migraine preventives. For CH prevention, galcanezumab has shown some promising findings and was recently approved for use in episodic cluster prevention. CGRP function‐blocking therapy not only demonstrates high efficacy and superior safety profile, but also improves headache frequency and quality of life. Convenient monthly dosing for the MAbs can further improve medication adherence, hence better headache control. With CGRP function‐blocking therapy showing efficacy even in individuals who failed other preventives, it has become an exciting new therapeutic option in the field of migraine and CH.

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“…This report suggested that erenumab 140 mg might have additional benefit compared with 70 mg. The ≥50% reduction in mean monthly migraine days was reported in 41.3% of those with ≥2 previous prevention trials in the 140‐mg group, 35.6% in the 70‐mg group, and 14.2% of the placebo group …”

Section: Other Erenumab Trials and Analysesmentioning

confidence: 94%

History and Review of anti‐Calcitonin Gene‐Related Peptide (CGRP) Therapies: From Translational Research to Treatment

2018

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Objective – To briefly describe the history of and available data on anti‐calcitonin gene‐related peptide (CGRP) therapies for headache. Background – CGRP was proposed as a target for primary headache therapies. Translational research involved moving from delineating the relationships between CGRP and primary headaches and the clinical development of anti‐CGRP treatments. The first anti‐CGRP treatment, an intravenous CGRP‐receptor antagonist or gepant, olcegepant, was described as effective in terminating migraines in humans in 2004. Methods – The author briefly reviews some of the pathophysiology and translational research that led to the development of the gepants initially and then subsequently to the anti‐CGRP and anti‐CGRP receptor monoclonal antibodies. All accessible randomized controlled trials, abstracts, platform presentations, and press releases on the monoclonal antibody trials are summarized. The trajectory from bench research to the approval of the first anti‐CGRP receptor monoclonal antibody for clinical use in migraine prevention, erenumab, is discussed, as well as potential clinical uses of the anti‐CGRP treatments. Results – The US Food and Drug Administration (FDA) approved erenumab, an anti‐CGRP receptor monoclonal antibody, for prevention of migraine May 17, 2018. At the time of this writing (May 2018), 2 other anti‐CGRP monoclonal antibodies have been submitted to the FDA for the indication of prevention of migraine, galcanezumab and fremanezumab. Galcanezumab has reportedly shown effectiveness in preventing episodic cluster headache as well, although has not yet been submitted to the FDA for this indication. Eptinezumab will likely be submitted to the FDA for prevention of migraine later in 2018. Two gepants, ubrogepant and rimegepant, have completed positive pivotal trials for acute treatment of migraine, but have not yet been submitted to the FDA for this indication. Conclusions – The development of anti‐CGRP therapies opens a new era in the acute and preventive treatment of primary headache disorders.

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Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study

Cited by 130 publications

References 11 publications

Positive response to galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double‐blind studies

Positive response to galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double‐blind studies

Targeting CGRP for the Prevention of Migraine and Cluster Headache: A Narrative Review

History and Review of anti‐Calcitonin Gene‐Related Peptide (CGRP) Therapies: From Translational Research to Treatment

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