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Monoclonal Antibody Therapies Plus OnabotulinumtoxinA Decrease Headache Days

Adding monoclonal antibody-based medication to treatment for patients whose migraine is not controlled by onabotulinumtoxinA reduces the number of headache days, researchers reported at the virtual annual scientific meeting of the American Headache Society.

Patients who received combined therapy reported an average of 8.69 monthly headache days, which represented a decrease of an average of 16.60 monthly headache days, reported Fred Cohen, MD, a resident physician in internal medicine at the Montefiore Medical Center and Albert Einstein College of Medicine in the Bronx, NY.

Dr. Cohen said that the difference translated to a highly significant 65.6 percent reduction from baseline (p=0.0001). The improvement also was achieved without a great cost in adverse events, he said.

"Only 13 patients or 8.5 percent of the total reported side effects to the novel calcitonin gene-related peptide monoclonal antibodies (CGRP) medications. Those adverse events were mainly constipation, injection site reactions, and/or fatigue," he said. Patients were administered the CGRP medications: fremanezumab, galcanezumab or erenumab.

"While our study does show patients having fewer monthly headache days with both onabotulinumtoxinA and a CGRP compared with onabotulinumtoxinA alone, it ultimately is a retrospective chart review," Dr. Cohen said. "That means this study suffers from weaknesses such as possible confounders and recall bias. Therefore, I do not think these data would be high enough quality to change or create a protocol."

"However," he added, "I do think this study provides insight for providers who have patients already receiving onabotulinumtoxinA that require further preventive therapy. Prior to this study, there was very little to no information on patients receiving both onabotulinumtoxinA and a CGRP. Part of that is because patients who were taking onabotulinumtoxinA were excluded from the CGRP trials. Our data show that adding a CGRP would provide a further reduction in monthly headache days and headache pain severity, as well as being safe and tolerable."

For the trial, Dr. Cohen and colleagues conducted a retrospective chart review of patients with chronic migraine receiving treatment with onabotulinumtoxinA who had been prescribed a CGRP medication. Inclusion criteria included adult patients who were diagnosed with chronic migraine, and were receiving onabotulinumtoxinA and a CGRP medication from May 2018 to May 2019. Patients were excluded if they received another new therapy during the study period or treatment with a CGRP medication for less than two months.

The researchers included 153 patients in the study. In addition to onabotulinumtoxinA, Dr. Cohen reported that 889 patients–or 58 percent of the group—were treated with erenumab, either 70 mg or 140 mg; 51 patients were taking galcanezumab, and 13 patients were receiving on fremanezumab.

Nearly three-fourths of the patients in the study reported a decrease in either monthly headache days or headache pain severity, with quantitative data documented in 66 patients. Of these 66 patients, the average monthly headache days prior to initiating onabotulinumtoxinA treatment was 25.30. After onabotulinumtoxinA treatment, an average decrease of 10.96 monthly headache days was reported, but patients continued to have an average of 14.34 monthly headache days despite successful treatment. After the addition of a CGRP medication, patients experienced a further decrease of 5.64 monthly headache days, an additional 22.3 percent reduction from onabotulinumtoxinA alone (p=0.0001).

"Our next step is to conduct a prospective chart review, which would provide higher quality data," Dr. Cohen said. "A randomized clinical trial would be a step I would like to take, for that provides the highest quality of data."

He suggested that more data is needed before considering a first-line CGRP therapy in patients with chronic migraine. "I do think it is a possibility," he said. "This would also benefit patients who would want an alternative to onabotulinumtoxinA injections. These injections could be cumbersome for patients due to the need to return to the clinic every three months to receive treatment, whereas a CGRP could be taken monthly or quarterly at home."

In commenting on the study, Robert Cowan, MD, the Higgins Professor of Neurology and Neurosciences and chief of headache medicine at Stanford School of Medicine in Palo Alto, CA, said: "These findings are compelling and they are also consistent with our own experience at Stanford and with that of many colleagues."

"Moreover, there is no theoretical reason for concern in combining the two therapies, although onabotulinumtoxinA does lower CGRP levels. However, to establish a firm evidence base for a protocol, a prospective study needs to be done," Dr. Cowan said.

Dr. Cowan was also cautious about using CGRP upfront. "Until we have data on the impact of these monoclonal antibodies in subpopulations over time, I would not be comfortable using them as a first-line treatment. Until we know the impact on patients who have monoclonal antibodies on board and then experience acute events such as stroke, myocardial infarction, bowel infarction, closed head trauma, etc., questions will remain. Similarly, we need data on the impact of monoclonal antibodies on patients with other comorbid chronic conditions such as arthritis, lung disease, and so forth."

Disclosures: Dr. Cohen had no disclosures. Dr. Cowan has received honoraria for serving as an advisory board member to Amgen, Alder, Allergan, and Teva.

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AHS Abstract: Cohen F, Armand C, Vollbracht S. Efficacy and tolerability of CGRP monoclonal antibody medications in patients with chronic migraine undergoing treatment with onabotulinumtoxinA.