NeuroVoices: Amaal Starling, MD, FAHA, FAAN, on Real-World Insights From the INFUSE Study of Eptinezumab

Despite the rapid expansion of calcitonin gene–related peptide (CGRP)–targeted therapies, a substantial proportion of patients with migraine continue to experience high disease burden after failure of one or more preventive options. While switching between subcutaneous monoclonal antibodies or oral gepants has demonstrated variable benefit, real-world data evaluating intravenous eptinezumab in this population have remained limited.

At the 2026 Headache Cooperative of the Pacific Annual Conference, investigators presented 6-month data from the ongoing real-world INFUSE study, evaluating IV eptinezumab in adults with migraine who had failed at least one prior CGRP-targeted preventive therapy. Among 111 participants completing 6 months of treatment, 44.1% achieved ≥50% reduction in monthly headache days, with a mean reduction of 6.8 days from a baseline of 20.0 monthly headache days. Additionally, 26.1% achieved >75% reduction, and patients reported an average increase of 6.3 additional “good days” per month.

Amaal Starling, MD, FAHS, FAAN, associate professor of neurology at Mayo Clinic and study author on INFUSE, spoke with NeurologyLive® about how clinicians should interpret these findings, the mechanistic rationale behind switching to IV therapy, and what this means for treatment sequencing and patient-centered endpoints in migraine trials.

NeurologyLive: How should clinicians interpret the magnitude of response in INFUSE, particularly in patients who had failed prior CGRP-targeted therapies?

Amaal Starling, MD, FAHS, FAAN: The INFUSE study is an ongoing, 12-month, real-world US effectiveness study evaluating the efficacy of IV eptinezumab in adults living with migraine who have found at least one or more anti-CGRP preventive treatments ineffective. This includes prior trials of preventive monoclonal antibodies as well as gepants for the prevention of migraine.

In this real-world study, it’s important to emphasize that not only had this population found at least one or more CGRP-targeted preventive treatment options ineffective, but they also had a high burden of disease. The vast majority had chronic migraine, and beyond that, the baseline monthly headache day burden was quite high at about 20 monthly headache days. So, this is a population of patients with a high burden of disease.

In fact, as we enrolled participants, we found that 55% of the individuals enrolled in the study had found three or more CGRP-targeted treatments ineffective prior to initiating IV eptinezumab. Again, this is a population that has tried a lot of different medications, including several CGRP-targeted preventive treatment options.

What we really wanted to know was: in this population, in the real world, is IV eptinezumab effective? We found that there was quite an early as well as sustained benefit. Forty-four percent of the cohort achieved at least a 50% reduction in monthly headache days. Twenty-six percent of the population achieved a higher level of monthly headache day reduction of 75%.

Another aspect of this study that I really love is that we focused on patient-centered outcomes, looking at good days per month and the Patient Global Impression of Change, which are very patient-centric. We found that those endpoints were also very positive in this study, even as early as seven days after initiation of IV eptinezumab.

Overall, we saw early, meaningful, and sustained benefits with IV eptinezumab in a highly treatment-experienced, high-burden population.

Why might patients respond differently after switching to IV eptinezumab?

IV eptinezumab is the only infusion-based CGRP-targeted therapy for the prevention of migraine, and the fact that it is an infusion really sets it apart. It reaches 100% bioavailability at the end of the infusion.

That allows individuals to have the full amount of the medication and the potential efficacy immediately after the infusion. We see that reflected in the reduction and improvement in symptoms, improvements in PGIC, and improvements as early as seven days in this study. In prior studies, we’ve seen improvement even earlier, sometimes on the day of infusion. That correlates with the fact that this is an infusion and reaches 100% bioavailability immediately.

The other important point is that with subcutaneous administration and oral medications, there is patient-to-patient variability in the amount and speed of absorption. When it is an infusion, it removes that variability in absorption. Every individual achieves 100% bioavailability. So it is very consistent from patient to patient.

I think those factors make a huge difference and really set IV eptinezumab apart in terms of early, effective, and sustained benefit.

What are the key clinical implications of INFUSE for treatment sequencing?

One of the things I like to emphasize to my patients about this study — and I’m already discussing it with them — is this shift toward more patient-centered outcomes. I love that I can take data and translate it directly to patients and talk about good days and being much improved or very much improved, rather than only talking about symptom burden and headache days.

This shift toward positive psychology is really important. It aligns with cognitive behavioral therapy and non-medication approaches to managing chronic disease. It helps patients redefine their experience beyond just counting symptoms.

Another important implication is that IV eptinezumab is robust, fast, and sustained. When I think about other neurologic diseases such as multiple sclerosis, the paradigm has shifted toward using very effective, very robust therapies early in the disease process to dampen disease severity quickly.

I believe we are moving into that paradigm in migraine as well. We need to use robust, highly effective therapies as early as we can to reduce disease severity and burden. Historically, we would try one therapy, then another, gradually escalating in effectiveness. I would like to see that paradigm shift toward earlier use of highly effective options.

In my clinical practice, I am increasingly moving IV eptinezumab earlier in the sequencing of treatment because I want to achieve robust and effective therapy as early as possible to reduce disease progression.

How can migraine trials better capture patient experience through their endpoints?

I believe it is our responsibility to continue publishing data that includes patient-centered outcomes and to elevate the importance of the patient voice. Many people argue that monthly headache days should always remain the primary endpoint. Some struggle with endpoints like good days, especially in real-world studies, because good days are defined by the patient.

The reason I love good days is precisely because they are defined by the patient. Migraine is not just a headache. It includes light sensitivity, sound sensitivity, motion sensitivity, nausea, vomiting, brain fog, and functional impairment. A good day captures all of that.

If we continue to show in real-world studies that good days and PGIC correlate with established endpoints such as monthly headache days and disability scales, we can build confidence in these patient-centered measures.

We need to continue presenting posters, publishing manuscripts, and elevating these endpoints. Over time, I hope they move from exploratory endpoints to secondary endpoints, and eventually perhaps even primary endpoints. That will require consistent publication, collaboration, and discussion with regulatory agencies.

There is also growing emphasis on patient-centered research through funding mechanisms such as PCORI, which elevates the patient voice. Leveraging those funding pathways will help move the field forward.

What does the future of precision medicine in migraine look like?

Precision or individualized medicine is the ideal scenario where we can identify before a patient tries a medication which therapy will be effective and which may cause side effects. Right now, most of our decision-making is based on characteristics of the medication rather than characteristics of the patient.

The goal is to incorporate patient characteristics such as genetics, clinical features, imaging findings, and laboratory studies. As more targeted therapies come into development, including PACAP-targeted therapies, this will become even more important.

We need large databases that integrate genetic information, imaging studies, laboratory data, and clinical characteristics. This is where AI and predictive modeling can help identify which patients are most likely to benefit from specific therapies.

What we have seen in both real-world and registrational studies is that a large number of individuals with migraine, including those with high disease burden and prior treatment failures, respond meaningfully to IV eptinezumab. That supports earlier use in appropriate patients.

But ultimately, the future lies in big data analysis and predictive modeling to identify which targeted treatments will benefit which targeted populations and to reduce the trial-and-error process that currently defines much of migraine care.

Transcript edited for clarity.