by Deena Kuruvilla, MD, FAHS

The title of this abstract is Efficacy and Tolerability of CGRP Monoclonal Antibody Medications in Patients with Chronic Migraine Undergoing Treatment with OnabotulinumtoxinA. The lead author is Fred Cohen, MD. The authors conducted this study based on an electronic medical record. Patients were identified by the electronic medical record between May 2018 to May 2019 at the Montefiore Headache Center. This was a retrospective chart review and patients were included if met the ICHD-3 criteria for chronic migraine, were adults, and were treated with onabotulinumtoxinA followed by a CGRP monoclonal antibody. They had to have at least two months of followup on the CGRP monoclonal antibody. Patients were excluded if treatment with the CGRP monoclonal antibody medication was <2 months, or they received another new therapy during the study period.

153 patients were enrolled in this study and further dividing the CGRP monoclonal antibodies that were used, erenumab was used in 58% of patients, galcanezumab was used in 33% of patients, and fremanezumab was used in 9% of patients, almost 91% of the cohort was female. And the average age was 47. 74% of patients in the study (114 out of 153 patients), reported a decrease in monthly headache days and/or headache pain severity within this cohort. After onabotulinumtoxinA treatment, an average decrease of 10.9 monthly headache days was reported, which was around a 43% reduction from baseline. But patients continued to have an average of 14 monthly headache days despite successful treatment.

After the addition of a CGRP monoclonal antibody medication, patients experienced a further decrease of 5.6 monthly headache days. That is an additional 22% reduction from onabotulinumtoxin treatment alone. With combined therapy. Patients reported an average of 8.7 monthly headache days for a total decrease of 16 monthly headache days. That's a 65.6% reduction from baseline. 13 patients, around 8.5%, reported side effects to CGRP monoclonal antibody medications. This included constipation, injection site reaction, and/or fatigue. This study suggests that patients on CGRP monoclonal antibody medications and onabotulinumtoxinA, can have a further reduction in their monthly headache days and pain severity when these two treatments are used at the same time. Future studies are certainly warranted to prove this hypothesis.

The results of this study align very closely with my experience in headache practice. I have been adding CGRP mAB (calcitonin gene-related peptide monoclonal antibody) therapies to onabotulinumtoxinA injections to provide patients with additional relief with a reduction in their monthly migraine days. With that said, it is difficult to provide solid recommendations to patients based on retrospective chart reviews. Some of the disadvantages of retrospective chart reviews are recall bias, possible missing data and difficulties controlling for confounding factors¹. This study does however create an interesting hypothesis that has implications for clinical practice. If the numbers in this study of almost 67% reduction in monthly headache days with combination therapy vs. 43% with onabotulinumtoxinA therapy alone, are reproducible in a prospective, randomized, placebo-controlled trial, I would consider that considerable relief in headache burden for people with chronic migraine. People with chronic migraine are less responsive to classic migraine preventive treatments when compared to people with episodic migraine². In the original PREEMPT protocol, the randomized, placebo-controlled onabotulinumtoxinA clinical trial, 49% of patients treated with the active treatment had a greater than or equal to 50% reduction in headache days after 1 treatment cycle and an additional 11% responded after the second treatment cycle³.

Combination treatment with onabotulinumtoxinA and CGRP mABs are certainly an attractive option for people with chronic migraine. Prior studies have measured serum levels of CGRP (calcitonin gene-related peptide) and other inflammatory markers as predictors of response to onabotulinumtoxinA therapy. Serum levels of CGRP were higher in onabotulinumtoxinA responders when compared with nonresponders⁴. Many of the existing medications we use such as blood pressure medications, seizure medications and anti-depressant medications often come with intolerable side effects 5. Just based on the side effect profiles and the exercise of taking one of these oral medications one to three times a day, a monthly/quarterly injection with a series of injections every 12 weeks may be favored by the patient. Studies have shown that adherence to oral migraine preventive medications is low at 6 months and drops further by 12 months⁶. Most patients also report to me that daily medications are often more burdensome than a monthly or quarterly injection or series of injections.

While patients and providers have interest in using combination treatment plans with onabotulinumtoxinA and CGRP mAb therapies, coverage by insurers is a hurdle. Many insurers have declined to cover both treatments if used simultaneously⁷.

Future studies are needed to solidify the impact of combination therapy versus monotherapy.

 

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References:

1. Hess, D. R. Retrospective studies and chart reviews. Respir. Care 49, 1171–1174 (2004).
2. D’Amico, D., Leone, M., Grazzi, L. & Bussone, G. When should ‘chronic migraine’ patients be considered ‘refractory’ to pharmacological prophylaxis? Neurol. Sci. 29 Suppl 1, S55–8 (2008).
3. Silberstein, S. D. et al. Per cent of patients with chronic migraine who responded per onabotulinumtoxinA treatment cycle: PREEMPT. J. Neurol. Neurosurg. Psychiatry 86, 996–1001 (2015).
4. Domínguez, C. et al. CGRP and PTX3 as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine: An Observational Study. Headache 58, 78–87 (2018).
5. Schwedt, T. J. Preventive Therapy of Migraine. Continuum  24, 1052–1065 (2018).
6. Hepp, Z. et al. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia 35, 478–488 (2015).
7. Ducharme, J. A Year After Approval, Migraine Drugs Are Changing Lives. But Insurance Battles Are Creating a Whole New Headache. Time https://time.com/5608386/cgrp-migraine-drugs-insurance/ (2019).