Data Suggest Efficacy of Erenumab in OnabotulinumtoxinA-Resistant Migraineurs

Treatment with erenumab led to improvements in pain, medication use, and quality of life in onabotulinumtoxinA (BoNTA)-resistant patients with chronic migraine (CM), according to study results published in The Journal of Headache and Pain.

Erenumab, a monoclonal antibody, was approved by the FDA in 2018 and is administered monthly via self-injection of a 70- or 140-mg dose. The treatment blocks the calcitonin gene-related peptide (CGRP) receptor, which is believed to play a crucial role in migraine.

Real-world data have suggested that erenumab can be effective in patients with more severe migraine phenotypes, like those with a history of treatment failure. However, because the treatment is more expensive than oral preventive agents and must be administered by trained health care providers, erenumab “is generally reserved for patients with more severe forms of migraine,” researchers wrote. Currently, “erenumab is deemed not to be cost effective within its marketing authorization and remains unavailable for patients” in England.

In an open-label audit of patients with CM, investigators analyzed the outcomes of erenumab treatment among those who had a prior unsatisfactory response to BoNTA. Previous data have shown that the 2 treatments combined led to significant reductions in monthly headache days (MHDs) and monthly migraine days (MMDs) in this patient population.

In the current study, conducted at a tertiary referral center in the United Kingdom, erenumab was provided under a commercial supply agreement free of charge. All participants met the International Classification of Headache Disorders (ICHD) definition of CM and had previous unsatisfactory responses to BoNTA, defined as a reduction of 30% or less in headache days following 2 treatments and/or lack of tolerability. Patients also had failed and/or had contraindications to 2 or more classes of preventive medications, and no participants took BoNTA and erenumab concurrently.

Headache diaries were used to measure patient response to erenumab, and a traffic light scoring system was used to grade headache severity. “Red days represented days with headaches which limited activities of daily living or which required use of triptans, amber days represented days with headaches but no limitation to activities of daily living, and green days represented headache-free days,” the authors explained. Participants also completed the patient health questionnaire 9 (PHQ-9), headache impact test 6 (HIT-6), and pain disability index (PDI).

A total of 98 patients were included in the final analysis, of whom 56 underwent a dose increase to 140 mg at a median of 2 months after treatment initiation. Prior to the study, 82% of patients had trialed greater occipital nerve injections, 33% had received peripheral neurostimulation, and 18% had received intravenous dihydroergotamine. Thirty-eight patients also met the definition of triptan overuse and 43 reported analgesic overuse.

Analyses revealed:

• Mean (SE) number of red days improved by −6.4 (0.67) days (95% CI, −7.7 to −5.1; P = .001), −6.8 (0.96) days (95% CI, −8.80 to −4.9; P = .001), and −6.5 (0.86) days (95% CI, −8.3 to −4.8; P = .001) at 3, 6, and 9 months, respectively.
• Repeated measures analysis of variance confirmed improvements in the number of red (P = .001), green (P = .001), triptan (P = .001), and painkiller (P = .001) days, as well as scores of the HIT-6 (P = .001), PHQ-9 (P = .001), and PDI (P = .001) across the duration of study.
• A total of 24 patients opted to discontinue erenumab during the study period due to perceived lack of benefit (18%) or adverse effects (5%), namely rash, palpitations, gastrointestinal upset, tightness in throat, and hypertension.

After 6 months, 84% of patients reported a response to erenumab and maximal benefit was observed in the first 4 months of treatment.

Because the analysis was not a placebo-controlled study, researchers were unable to infer causality, and drop-outs and incomplete data mark limitations to the study.

“We feel our cohort is representative of the small minority of patients with difficult-to-treat chronic migraine who do not respond to readily available therapies (i.e. non-CGRP treatments),” the authors concluded. “Placebo-controlled trials in this population are required to confirm these findings.”

Reference

Talbot J, Stuckey R, Crawford L, Weatherby S, Mullin S. Improvements in pain, medication use and quality of life in onabotulinumtoxinA-resistant chronic migraine patients following erenumab treatment—real world outcomes. J Headache Pain. 2021;22(1):5. doi:10.1186/s10194-020-01214-2