Vyepti (eptinezumab)

Vyepti

This blog post will be written in the Wiki Journal Club format. As such, it will be more geared to the medical community than the lay public. However, I do my best to explain what the findings mean. All sources are linked at the bottom, as well.

The primary article explored here is the PROMISE-2 study.

Clinical Question

Among adults with episodic or chronic migraine, is eptinezumab infusion superior to placebo in reduction of monthly migraine days and improvement in QOL?

• Population: Adults with chronic migraine.

• Intervention: Eptinezumab (100 mg or 300 mg) administered via intravenous infusion.

• Comparison: Placebo.

• Outcome: Reduction in mean monthly migraine days (MMDs), improvement in quality of life, and safety profile.

Bottom Line

Eptinezumab significantly reduces MMDs in adults with chronic migraine, offering a rapid and sustained preventive treatment option with a favorable safety profile.

Major Points

• Eptinezumab, targeting the CGRP pathway, demonstrated efficacy in reducing MMDs in chronic migraine patients, underscoring its role in migraine prevention.

• The study was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, reinforcing the robustness of the evidence.

• Implementation in clinical practice would involve considering eptinezumab for patients with frequent migraine days unresponsive to other treatments, factoring in its rapid onset of action and safety profile.

Guidelines

• Individuals w/hx of significant CV disease or any clinically significant concurrent medical condition were excluded from participation in this study. 

• This study was designed for consistency with 2018 IHS guidelines related to clinical trials.

Design

• Trial type: Phase 3, multicenter, randomized, double-blind, placebo-controlled.

• N=1072 patients received treatment.

• Settings: 128 sites across 13 countries.

• Enrollment: November 30, 2016, to April 20, 2018.

• Mean follow-up: Up to 1 year.

• Primary outcome: Reduction in monthly migraine days (MMDs).

Population

• Inclusion: Adults 18/65 with chronic migraine.

• Exclusion: Significant comorbid pain disorders, untreated psychiatric conditions, etc.

• Baseline Characteristics: Predominantly female and white, with a balanced migraine history across treatment groups.

Interventions

• Eptinezumab administered as a 100 mg or 300 mg dose via intravenous infusion every 12 weeks, compared against placebo.

Outcomes

• Primary Outcome: Both eptinezumab doses significantly reduced MMDs compared to placebo over weeks 1-12. In some cases, efficacy was seen as early as Day 1. 

• Secondary Outcomes: Included ≥75% and ≥50% migraine responder rates, with eptinezumab showing superior performance over placebo.

• Subgroup Analysis: Efficacy consistent across various demographic and clinical subgroups.

• Adverse Events: Most common were nasopharyngitis and upper respiratory tract infections, generally mild.

• NNTH (d-AE) for 100 mg group was 6515; for 300 mg group it was 58.

• NNTB (50%) for 100 mg group was 6; for 300 mg group it was 5.

• Post-hoc Analysis:

• Across 24 wks of tx, eptinezumab reduced acute medication use for headache compared with placebo in both patients with CM as well as those with MOH (baseline 21 days/mo to 10 days/mo with either 100 or 300 mg). (Marmura et al., 2021)

• Individuals from PROMISE-2 with suboptimal first dose response who were second-dose responders was 29%, suggesting that those who don’t see ≥50% MMD response to their first dose of eptinezumab may still benefit from a second dose. (Schim et al., 2022)

Criticisms

Long-term safety data and comparative efficacy studies with other CGRP inhibitors both are omitted. 

Funding

Funded by Lundbeck Seattle BioPharmaceuticals, indicating potential for bias that should be considered when interpreting results.

Further Reading

• Across PROMISE-1 & PROMISE-2, ~50-60% of those treated with one dose of eptinezumab saw ≥50% MMD reduction.

• Eptinezumab was given to nine adolescent patients with CM and two with NDPH. The drug was well tolerated at both the 100 and 300 mg doses and resulted in significant decreases in patient-reported symptoms. (Zorilla et al., 2023)

• There is only one study comparing eptinezumab with the other CGRP mAbs, and it found that there is no evidence to suggest that one antibody may be superior to the others in terms of effectiveness, both in CM or EM patients. (Saccà et al., 2023)

Reference List:

Drellia, K., Kokoti, L., Deligianni, C. I., Papadopoulos, D., & Mitsikostas, D. D. (2021). Anti-CGRP monoclonal antibodies for migraine prevention: A systematic review and likelihood to help or harm analysis. Cephalalgia : an international journal of headache, 41(7), 851–864. https://doi.org/10.1177/0333102421989601

Lipton, R. B., Goadsby, P. J., Smith, J., Schaeffler, B. A., Biondi, D. M., Hirman, J., Pederson, S., Allan, B., & Cady, R. (2020). Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology, 94(13), e1365–e1377. https://doi.org/10.1212/WNL.0000000000009169

Marmura, M. J., Diener, H. C., Cowan, R. P., Tepper, S. J., Diamond, M. L., Starling, A. J., Hirman, J., Mehta, L., Brevig, T., & Cady, R. (2021). Preventive migraine treatment with eptinezumab reduced acute headache medication and headache frequency to below diagnostic thresholds in patients with chronic migraine and medication-overuse headache. Headache, 61(9), 1421–1431. https://doi.org/10.1111/head.14206

Saccà, F., Braca, S., Sansone, M., Miele, A., Stornaiuolo, A., De Simone, R., & Russo, C. V. (2023). A head-to-head observational cohort study on the efficacy and safety of monoclonal antibodies against calcitonin gene-related peptide for chronic and episodic migraine. Headache, 63(6), 788–794. https://doi.org/10.1111/head.14528

Schim, J. D., Anderson, C., Brunner, E., Hirman, J., Ogbru, A., Cady, R., & McGill, L. (2022). Likelihood of response with subsequent dosing for patients with migraine and initial suboptimal response with eptinezumab: A post hoc analysis of two placebo-controlled randomized clinical trials. Headache, 62(5), 558–565. https://doi.org/10.1111/head.14302

Zorrilla, N., Gelfand, A. A., & Irwin, S. L. (2023). Eptinezumab for adolescents with chronic refractory headache: A retrospective chart review. Headache, 63(1), 177–182. https://doi.org/10.1111/head.14452