Further studies are needed to confirm the additional reductions in monthly headache days observed in patients with migraine who were treated with onabotulinumtoxinA and an add-on CGRP agent.
Fred Cohen, MD
New data from a retrospective chart review of patients with chronic migraine receiving treatment with onabotulinumtoxinA who have been prescribed a calcitonin gene-related peptide (CGRP) monoclonal antibody medication suggest that the new class of medicines are safe and effective for those who require additional preventive treatment.1
Ultimately, in a cohort of 153 patients treated with onabotulinumtoxinA, 66 continued to have 14.3 monthly headache days despite significant reductions from baseline headache days prior to treatment with onabotulinumtoxinA (baseline, 25.3 days; reduction, 10.9 days [43%]; P <.0001). The add-on of a CGRP therapy was associated with an additional decrease of 5.6 days, equating to an additional 22.3% reduction (95% CI, 4.5—6.7; P <.0001) in monthly headache days.
Of the 153-patient study population, 88 (58%) were treated with erenumab (Aimvoig; Novartis), 51 (33%) were treated with galcanezumab (Emgality; Eli Lilly), and 14 (9%) were treated with fremanezumab (Ajovy; Teva). The data were presented by Fred Cohen, MD, internal medicine resident physician in the department of medicine at Montefiore Health System, at the American Headache Society (AHS) Virtual Annual Scientific Meeting on June 13, 2020.
“We have shown that CGRP monoclonal antibodies are an effective and well-tolerated treatment option for patients with chronic migraine who undergoing treatment with onabotulinumtoxinA but require additional preventive therapy,” Cohen said in the presentation. “The addition of a CGRP monoclonal antibody provided statistically significant less monthly headache days, however, this was a retrospective chart review, which is hindered by elements such as recall bias, therefore future prospective studies are warranted for higher-quality data.”
In total, those treated additionally with CGRP medicines experienced an overall reduction of 16.6 monthly headache days (95% CI, 13.8—19.3; P <.0001) from baseline pre-onabotulinumtoxinA treatment. In total, 13 patients (8.5%) reported adverse effects associated with the CGRP medications that included constipation, injection site reaction, and/or fatigue.
“The data for efficacy outcomes and safety profile when adding a CGRP monoclonal antibody to patients who are already receiving onabotulinumtoxinA is limited,” Cohen explained. “This is, in part, due to the fact that during the clinical trials for CGRP monoclonal antibodies, patients treated with onabotulinumtoxinA were excluded.”
When exploring the reductions with each CGRP agent, the observations were similar. The erenumab, galcanezumab, and fremanezumab groups experienced baseline monthly headache days of 26.1, 24.9, and 26.2 days, respectively, and then reductions of 11.3 (monthly headache days, 14.8), 10.3 (monthly headache days, 14.6), and 11.7 days (monthly headache days, 14.5) with onabotulinumtoxinA. After the introduction of erenumab, those on onabotulinumtoxinA experienced a further reduction of 5.5 days (monthly headache days, 9.3), while those introduced to galcanezumab experienced reductions of 5.3 days (monthly headache days, 9.3), and to fremanezumab experienced reductions of 8.7 days (monthly headache days, 5.8).
“We see that there is very little variance at baseline and when onabotulinumtoxinA was added, and while erenumab and galcanezumab have similar decreases in monthly headache days from onabotulinumtoxinA alone, we do see a further increase with fremanezumab,” Cohen said. “However, it is important to remember that fremanezumab made up a much smaller portion of the patient population, and therefore, this value has less power.
Notably, of the 153 patients included, 114 (74.5%) reported a decrease in monthly headache days or headache pain severity on onabotulinumtoxinA.
Earlier this year at the American Academy of Neurology (AAN) 2020 Annual Meeting, data were accepted from a number of analyses of the COMPEL study, including an assessment which sought to ascertain the proportion of those with chronic migraine that achieved a reduction of <15 monthly headache days following onabotulinumtoxinA treatment.2
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 (P <.001).2
While not entirely successful for the full population in the AHS 2020 abstract, those long-term efficacy findings for onabotulinumtoxinA may be troubling for clinicians in the context of the findings from a recent anonymous clinician survey published in May. Those data implied that the adherence to proper PREEMPT protocol for the use of onabotulinumtoxinA injections in the treatment of migraine may be lower than believed. Of the 182 clinician respondents to the survey, 77.5% (n = 141) reported that they did not always follow the PREEMPT protocol, suggesting that perhaps there may be a need for an advisory protocol containing more evidence and a discussion of the reasoning for specific recommendations might be more helpful than the current prescriptive protocol.3
Conducted by Begasse de Dhaem et al., the study also identified that more than half of the physicians surveyed changed the number of injections, the total units of medicine, and the location of the injection site. Similar results were observed in that fewer than 20% of the respondents noted that they rarely made alterations—more than 50% replied that they frequently did so.
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1. Cohen F, Armand C, Vollbracht S. Efficacy and Tolerability of CGRP Monoclonal Antibody Medications in Patients with Chronic Migraine Undergoing Treatment with OnabotulinumtoxinA. Headache. 2020;60(S1 suppl). 1-156. doi: 10.1111/head.13854
2. Blumenfeld AM, Luo L, Lipton R. Benefits of Long-Term OnabotulinumtoxinA Treatment in Chronic Migraine: Results from the COMPEL Study. Neurology. 2020;94(15 Suppl): 1694.
3. Begasse de Dhaem O, Gharedaghi MH, Rizzoli P. Modifications to the PREEMPT protocol for onabotulinumtoxinA injections for chronic migraine in clinical practice. Headache. Published online April 25, 2020. doi: 10.1111/head.13823