Migraine remains a leading cause of neurological disability worldwide, imposing an immense burden on both patients and healthcare infrastructure. Clinicians have traditionally reserved calcitonin gene-related peptide pathway inhibitors for refractory cases. However, recent evidence is shedding new light on using erenumab migraine prophylaxis earlier in the therapeutic pathway. Understanding how treatment resistance influences subsequent therapeutic success is critical for optimizing long-term preventive strategies in clinical practice.

Understanding Erenumab Migraine Prophylaxis Across Lines of Care

Erenumab is a fully human monoclonal antibody that selectively targets the canonical calcitonin gene-related peptide receptor. Regulatory authorities initially approved erenumab in Germany in 2018 for migraine prevention. At that time, strict reimbursement guidelines restricted prescription exclusively to patients with drug-resistant migraine who had failed multiple standard oral preventives. Consequently, clinicians could only administer this novel biologic after patients exhausted conventional options such as beta-blockers, topiramate, flunarizine, and amitriptyline. Over time, evolving healthcare policies and expanding clinical experience permitted earlier initiation, allowing patients with only a single prior failure to access targeted therapy. As earlier initiation of effective preventive therapy may prevent disease chronification and improve quality of life, comparing outcomes across treatment lines has become an urgent clinical question.

Study Design: Single Versus Multiple Prior Treatment Failures

To examine this clinical question, investigators conducted a retrospective single-center observational study analyzing 196 adult patients diagnosed with episodic or chronic migraine. All included participants received monthly subcutaneous erenumab for at least three months. Researchers categorized patients into two distinct treatment cohorts based on their documented therapeutic history. The multiple prior therapy group comprised 140 individuals who had previously failed between two and six preventive regimens due to inadequate efficacy or poor tolerability. In contrast, the single preventive therapy group included 56 individuals who had failed only one prior preventive medication before starting erenumab. The primary clinical endpoint was achieving a meaningful treatment response, defined as a 50% or greater reduction in monthly headache days over the three-month evaluation period.

Key Findings: Real-World Clinical Efficacy and Odds Ratios

The study results revealed substantial clinical benefits across both patient cohorts. Specifically, 35.7% of patients in the single preventive therapy group achieved a 50% or greater reduction in monthly headache days at three months. Similarly, 30.7% of patients in the multiple prior therapy group achieved this primary therapeutic response threshold. Statistical analysis demonstrated no significant difference in treatment effectiveness between the two groups. To ensure robust findings, researchers performed multivariate logistic regression adjusting for baseline characteristics and potential confounders. In the adjusted regression model, single prior therapy status was not significantly associated with treatment success (adjusted OR 1.39, 95% CI 0.53–3.69; p = 0.5). Sensitivity analyses utilizing propensity score weighting and LASSO variable selection further corroborated these primary findings.

Clinical Implications for Migraine Management in Practice

These real-world observations deliver valuable reassurance for clinicians treating difficult migraine phenotypes. The findings suggest that therapeutic response to erenumab is not solely dictated by the sheer quantity of previous drug failures. Therefore, patients who have cycled through multiple conventional oral prophylactic agents still retain a meaningful likelihood of responding robustly to receptor-targeted monoclonal antibodies. Furthermore, earlier deployment of erenumab in patients failing a single conventional preventive provides consistent short-term therapeutic relief without losing efficacy. Given that poor tolerability and non-adherence frequently derail traditional oral preventive strategies, targeted biologics offer an effective alternative early in disease management. Clinicians should evaluate patient burden comprehensively rather than viewing extensive drug failure as a negative predictor of biologic response.

Methodological Considerations and Future Clinical Horizons

While these findings provide pragmatic clinical insights, clinicians must interpret the conclusions within the context of the study methodology. The retrospective, single-center design naturally introduces potential selection bias, and the modest sample size yielded relatively wide confidence intervals. Consequently, larger prospective multicenter registries and randomized clinical trials are required to confirm these observations over extended follow-up durations. Moreover, assessing patient-reported outcome measures, acute medication reduction, and functional disability will offer a more comprehensive appraisal of treatment benefit. In routine practice, identifying predictive biomarkers and individualizing treatment pathways remain the primary goals for improving migraine care globally. Ultimately, targeted biologics continue to redefine standard care paradigms for patients with episodic and chronic migraine.

Frequently Asked Questions

What was the primary outcome measured in the study?

The primary outcome was achieving a clinically meaningful treatment response, defined as at least a 50% reduction in monthly headache days from baseline after three months of erenumab therapy across both study groups.

Did patients with multiple treatment failures respond poorly to erenumab?

No, patients who failed multiple previous preventives demonstrated a 30.7% response rate, which was not statistically significantly different from the 35.7% response rate observed in patients who had failed only one prior therapy.

What are the main limitations of this real-world study?

The primary limitations include its retrospective single-center design and relatively modest sample size of 196 patients. These factors contributed to wide statistical confidence intervals and highlight the need for larger prospective validation trials.

Disclaimer: This content is for informational and educational purposes only. It is not intended to provide medical advice, diagnosis, or treatment. Healthcare professionals should make clinical decisions based on their independent clinical judgment and individualized patient assessments. Refer to the latest local and national guidelines for clinical practice.

References

1. Schmidt C et al. Real-world short-term effectiveness of erenumab after single versus multiple prior preventive treatment failures. BMC Neurol. 2026 Aug 28. doi: 10.1186/s12883-026-05311-8. PMID: 42661173.
2. Reuter U, Goadsby PJ, Lanteri-Minet M, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392(10161):2280-2287.
3. Ashina M, Tepper S, Brandes JL, et al. Long-term efficacy and safety of erenumab in migraine prevention: results from a 5-year open-label extension. Eur J Neurol. 2021;28(5):1716-1725.