Real-World Patient Experience With Erenumab for the Preventive Treatment of Migraine

Jennifer Robblee, MD, MSc; Katrina L. Devick, PhD; Natasha Mendez, APRN; Jamie Potter, APRN; Jennifer Slonaker, APRN; Amaal J. Starling, MD

Disclosures

Headache. 2020;60(9):2014-2025. 

In This Article

Abstract and Introduction

Abstract

Background: Erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, has been well tolerated with good efficacy for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 clinical trials. Limited post-market observations are available to validate these findings in a real-world tertiary headache clinic population with complex comorbidities and refractory migraine.

Objective: The goal of this study is to demonstrate the real-world performance of erenumab among patients in a tertiary care headache clinic by describing patient selection, experience, and clinical characteristics after 6 months of erenumab therapy.

Methods: A retrospective, exploratory, observational study was conducted on patients receiving at least 1 erenumab injection (70 or 140 mg). Baseline data obtained by chart review and telephone calls were compared to 6-month follow-up telephone calls. The primary outcome was the reduction in self-reported headache days per month at baseline compared to 6 months for those with complete 6-month data. The significance level was set at P < .05. Secondary analyses explored the distribution of headache severity, responder rates, Migraine Disability Assessment scores, adverse effects, ineffective preventives, comorbidities, wearing-off, and discontinuation.

Results: Of the 101 patients who consented to participate, 89.1% (90/101) were women, and the mean age of all patients was 49 years (range, 19–80 years). At baseline, 94.1% (95/101) of patients had chronic migraine, 5.0% (5/101) had episodic migraine, and 18.8% (19/101) had medication overuse headache. The mean (SD) number of baseline headache and migraine days per month for the entire cohort were 24.3 (8.2) and 18.2 (9.3) days, respectively. Participants had numerous comorbidities and had tried a mean of 11.2 unique oral medications and 4.8 unique medication categories before receiving erenumab, including 83.2% (84/101) who had also received onabotulinumtoxinA. Six-month post-erenumab follow-up data were available for 42.6% (43/101) of participants. For these 43 participants, the number of headache days per month decreased significantly by 6.5 days from a baseline mean (SD) of 24.8 (6.47) days to 18.3 (12) days at 6-month follow-up (P < .001); similarly, the monthly migraine days decreased significantly by 8.4 days from a baseline mean of 19.1 (9.3) days to 10.7 days at 6-month follow-up (P < .001). The 50% responder rate was 34.9% (15/43) for monthly headache days and 54.8% (23/43) for monthly migraine days. Of all 101 participants, 28 (27.7%) discontinued erenumab, primarily because it was ineffective (39.3%, 11/28) or because of adverse effects (42.9%, 12/28).

Conclusion: This post-market observational study of patient experience describes response to erenumab in a real-world tertiary headache clinic with a complex patient population. Overall, these complex patients had a significant positive clinical response to erenumab, but with high rates of discontinuation. This study also noted a 1-week wearing-off response and high rates of constipation. Further post-market studies are needed to better characterize patient selection and real-world response to erenumab.

Introduction

Calcitonin gene-related peptide (CGRP) is a key neuromodulator in the pathophysiology of migraine and cluster headache. CGRP receptors are located diffusely throughout regions of the nervous system that are associated with migraine pathophysiology, including the cortex, subcortical regions, brainstem, meninges, and trigeminal pathways (peripherally, dorsal root ganglia, trigeminocervical complex, and spinal cord).[1] CGRP is increased in extracerebral circulation during migraine and cluster headache attacks, but not during tension-type headaches.[2–4] Current migraine treatments, such as onabotulinumtoxinA, decrease CGRP in patients with chronic migraine, and triptans acutely reduce CGRP levels.[5,6] Erenumab, a monoclonal antibody specific to the CGRP receptor, was developed for preventive treatment of episodic and chronic migraine and released in May 2018 after US Food and Drug Administration approval.

In a meta-analysis, CGRP monoclonal antibodies were shown to reduce monthly migraine days (MMD), to reduce the use of abortive treatment, and to be safe compared with a placebo.[7] Phase 1 trials showed that erenumab was well tolerated, including when combined with triptans; also, cardiovascular safety was demonstrated in patients with stable angina.[8–10] In other studies, erenumab was well tolerated; injection-site reactions and constipation were the main adverse effects, affecting approximately 3% of patients.[8,9,11–15] Phase 2 and phase 3 trials of erenumab as a preventive treatment for episodic migraine with open-label extension and a phase 2 trial of erenumab for chronic migraine demonstrated a significant reduction in MMD, a 50% responder rate of 30–65%, and reduced abortive use.[12,13,15–17]

Since its release in 2018, limited post-market studies of erenumab are available to validate phase 2 and 3 studies in a real-world population where patients have complex comorbidities; multiple, often refractory, headache types; a large number of treatment failures; and concurrent treatments, including onabotulinumtoxinA. Robbins reported on a retrospective study in 2019 of 220 patients with chronic migraine receiving erenumab with the primary outcome being relief within 3 months.[18] He found that 43% of patients had 0–30% relief, 34% had 30–70% relief, and 24% had 70–100% relief. None of the erenumab trials have explored other headaches conditions, including posttraumatic headache, trigeminal autonomic cephalgia, or specific migraine phenotypes. Galcanezumab and fremanezumab, the other two currently available CGRP monoclonal antibodies, have both been studied to treat cluster headache with negative results for chronic headache; however, galcanezumab was recently approved for the indication of episodic cluster headache.[19]

In addition to the limited real-world experience with erenumab in tertiary care headache clinics, common clinical concerns need to be addressed in post-market analyses of this treatment. Older patients were excluded from the trials of erenumab, with cut-off age ranging from 50 to 65 years;[8,9,11–15] however, the safety study of erenumab in participants with cardiovascular disease during the treadmill test was tested among participants with a median age of 65 years but allowed those up to age 85 years. An additional safety concern related to the real-world use of erenumab is the concurrent use of biologics, which was not reported in the trials noted above, but is a common safety concern in clinical practice. The presence of a wearing-off effect similar to that seen clinically with onabotulinumtoxinA injections was also not reported in erenumab trials. While published studies reported low dropout rates, in standard clinical practice, the availability of other CGRP antibodies and the complication of drug insurance coverage or access may contribute to whether patients receive treatment long term.

This retrospective observational study provides a post-market analysis of erenumab's real-world performance among patients in the first 6 months after the initial dose in a tertiary care headache clinic with 9 providers. These were often patients in whom more than 10 unique medications have failed, and they also often had multiple headache diagnoses and comorbidities. Many of these patients had chronic daily headache, which was typically not studied in the monoclonal antibody clinical trials. We hypothesized that the real-world patient experience with erenumab would match clinical trial results; however, we expected, based on our clinical experience, that patients would have higher rates of adverse effects. While observational, this study may help guide clinicians on how patients in a tertiary care setting respond to erenumab.

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