Andrew Blumenfeld, MD

"In chronic migraine, the brain is sensitized, and it takes time to switch up these overactive pathways. We want to follow that, probably over a 6- to 12-month treatment period. We’re looking at a complicated trial because it’s going to be long duration.”

Investigators recently conducted a retrospective, longitudinal chart review of adults with chronic migraine (CM) treated with 2 or more consecutive onabotulinumtoxinA (Botox; Allergan/AbbVie) before at least 1 month of onabotulinumtoxinA plus calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb). Led by Andrew Blumenfeld, MD, patients demonstrated clinically meaningful treatment benefits with onabotulinumtoxinA alone and additive benefits after adding CGRP mAb.

Adverse events were reported in 28% of patients, with no new safety signals identified. The investigators concluded that more real-world studies and controlled trials are needed to further quantify potential benefits of this multimodal treatment paradigm. Blumenfeld, director of the Headache Center of Southern California, told 

that a combination approach using onabotulinumtoxinA and atogepant, an investigational CGRP, would be an interesting study considering the impressive response rates atogepant has shown in clinical trials.

He sat down in this interview to discuss more about the potential research opportunities for these types of multimodal treatment strategies, the build of these clinical trials, and why they need plenty of time to fully show efficacy.

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The director of the Headache Center of Southern California discussed research opportunities for layered treatment approaches in migraine. 

Potential Layered Migraine Treatment Approaches to Research: Andrew Blumenfeld, MD

"Think about migraine freedom. We need the payers to think about it because if it gets the patient out of the emergency room and back to work quicker, they will save money in the long run. That’s if they allow us to do these combinations, which are good for the patients. It’s a no-brainer. Unfortunately, we need data to change the system.”

Using a layered treatment approach with onabotulinumtoxinA (Botox; Allergan/AbbVie) and calcitonin gene-related peptide (CGRP) monoclonal antibody, data has indicated that there is an additional clinically meaningful improvement in headache frequency and migraine-related disability compared with a singular use of onabotulinumtoxinA. Lead author Andrew Blumenfeld, MD, and colleagues recently presented these findings at the 

2021 American Headache Society (AHS) 63rd Scientific Annual Meeting

Conducting trials that utilize these types of layered methods have become more relevant in recent years, but often come with complications. Blumenfeld, director of the Headache Center of Southern California, notes that these complications stem from funding and permission from drug companies, as well as choosing the right drugs. He added that the importance of these trials and the doors they open in research should not go unnoticed.

Blumenfeld discussed the complexities that come with conducting trials that incorporate a layered approach. He also stressed that new drug development isn’t always necessary, but rather combining existing products in a rational way is a worthwhile endeavor to hopefully reaching a cultural migraine freedom.

The director of the Headache Center of Southern California shared his thoughts on the factors and barriers that go into conducting trials that treat patients with migraine with multiple drugs. 

Complexities in Conducting Combination Migraine Therapy Trials: Andrew Blumenfeld, MD

"If you had 4 bad days a month, you’re missing 6 weeks of productive activity in a year. If you got up to 8, you’re missing 12 weeks out of the year. That’s a lot of time. There’s a cost that comes with that.”

Andrew Blumenfeld, MD, and colleagues recently conducted research that evaluated the real-world safety and potential benefits of adding a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) to onabotulinumtoxinA (Botox; Allergan/AbbVie) treatment in patients with chronic migraine. All patients included were aligned with the American Headache Society’s (AHS) position statement released in 2019, which states that a CGRP mAb may be added to 1 or more established treatments based on clinical judgement.

2021 Virtual AHS 63rd Annual Scientific Meeting

, June 3-6, showed that the combination of treatments is safe and well-tolerated, and was associated with clinically meaningful improvements in headache frequency and migraine-related disability. Blumenfeld, director of the Headache Center of Southern California, said that clinicians should feel comfortable directly applying this data into their own clinical care, considering the safety of the drugs observed have already been FDA-cleared.

Blumenfeld expressed his optimism in implementing the research into clinical care but noted that insurance companies oftentimes disrupt the process of allowing patients to receive a layered treatment approach to which they claim is experimental due to the “lack of data.”

The director of the Headache Center of Southern California provided insight on how a layered treatment approach to chronic migraine can be directly implemented into clinical care. 

Applying Data on CGRP, OnabotulinumtoxinA Combination to Clinical Practice: Andrew Blumenfeld, MD

"On average, what we saw happening across this year-long treatment is an additional 4-day reduction [in monthly headache days], from 12 to 8. That’s interesting that it didn’t go to zero. If it had gone to zero, you might have argued that the monoclonal antibody was the driving force that wiped out the headache and that you don’t need the Botox.”

Led by Andrew M. Blumenfeld, MD, a study presented at the 

2021 American Headache Society 63rd Annual Scientific Meeting

, June 3-6, evaluated the real-world safety and benefits of combination treatment with a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) and onabotulinumtoxinA (Botox; Allergan/AbbVie) in a cohort of patients with chronic migraine. A total of 172 patients were treated with 2 or more consecutive cycles of onabotulinumtoxinA with at least 1 month of subsequent combination treatment with a CGRP mAb and onabotulinumtoxinA.

Results showed that the dual treatment was well tolerated, with no new safety signals identified. The combination was associated with additional clinically meaningful improvements in headache frequency and migraine-related disability compared with onabotulinumtoxinA alone.

Blumenfeld, director of the Headache Center of Southern California, sat down with 

 to discuss the study and the implications of the results for clinical practice. 

The director of the Headache Center of Southern California discussed his research from AHS 2021 which evaluated safety and efficacy of combined treatment with CGRPs and onabotulimtoxinA. 

Real-World Use of CGRPs in Combination With OnabotulinumtoxinA: Andrew M. Blumenfeld, MD

“We don’t think of chronic migraine as a disease that disappears. We consider it like hypertension—if you control hypertension, you’re on a treatment, your blood pressure reading is normal. That’s how we looked at this group of patients. You had 15 days of headache or more, 22 days on average, and now you’re well-controlled and have less than 15 headache days per month.”

American Academy of Neurology (AAN) 2020 Annual Meeting

, data were accepted from a number of analyses the COMPEL study, including an assessment which sought to ascertain the proportion of those with chronic migraine that achieved a reduction to <15 monthly headache days following onabotulinumtoxinA treatment in the study.

All told, an increasing proportion of treated individuals achieved that mark of <15 headache days over time: 56% (302 of 539 patients) did so at Week 24, 69% (292 of 423 patients) at Week 60, 70.2% (262 of 373 patients) at Week 84, and 74.3% (226 of 304 patients) at Week 108. Additionally, a large majority of those who hit that mark met the criteria for ≥50% responder rates. In total, 70.9% (214 of 302) did so at Week 24, 78.1% (228 of 292) at Week 60, 80.5% (211 of 262) at Week 84, and 83.2% (188 of 226) at Week 108. The mean change in moderate/severe MHDs was also statistically significant compared to baseline values for these patients at all time points (

, study author Andrew Blumenfeld, MD, director, Headache Center of Southern California, spoke to the importance and impact of these results.

Blumenfeld offered his perspective on the findings of the study, as well as what these data might suggest about how onabotulinumtoxinA fits into the shifting landscape of chronic migraine care with the introduction of the monoclonal antibodies against calcitonin gene-related peptide (CGRP).

Blumenfeld AM, Luo L, Lipton R. Benefits of Long-Term OnabotulinumtoxinA Treatment in Chronic Migraine: Results from the COMPEL Study. 

The director of the Headache Center of Southern California discussed the findings of the study, as well as what these data might suggest about how onabotulinumtoxinA fits into the shifting landscape of chronic migraine care.

Andrew Blumenfeld, MD

Articles

Potential Layered Migraine Treatment Approaches to Research: Andrew Blumenfeld, MD

Complexities in Conducting Combination Migraine Therapy Trials: Andrew Blumenfeld, MD

Applying Data on CGRP, OnabotulinumtoxinA Combination to Clinical Practice: Andrew Blumenfeld, MD

Real-World Use of CGRPs in Combination With OnabotulinumtoxinA: Andrew M. Blumenfeld, MD

Andrew Blumenfeld, MD: Long-Term OnabotulimuntoxinA Use in the COMPEL Study

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