Preventive migraine treatment in mitochondrial diseases: a case report of erenumab efficacy and literature review

Migraine is a frequent condition in patients suffering from mitochondrial diseases, with a higher prevalence than in the general population [1]. The overall prevalence of migraine in the mitochondrial population observed in our Neuromuscular Centre was 35.5% [1]. The therapeutic approach in subjects affected by these neurogenetic disorders can be particularly difficult, due to frequent comorbidities and possible poor tolerance to drugs commonly used for headache [2, 3].

Here, we report the case of a patient affected by a mitochondrial disease who was safely and effectively treated with erenumab for migraine prophylaxis.

Over her long history of migraine, the patient had undergone several first-line prophylaxis treatments belonging to different pharmacological categories, which had proved ineffective or were poorly tolerated. In particular, among the pharmacological approaches, the patient was treated with amitriptyline (20 mg per day) and propranolol (up to 80 mg per day), both ineffective; cinnarizine (50 mg per day), discontinued for a marked increase in daytime sleepiness; flunarizine (5 mg per day) suspended after about 10 days for akathisia, which persisted for more than 1 month after discontinuation of this drug. Non-pharmacological treatments have not been used. Furthermore, symptomatic therapies both specific (zolmitriptan and eletriptan, effective but with high recurrence of the attacks) and non-specific (paracetamol and ketoprofen were poorly effective, while ibuprofen was effective) have been tried.

On the basis of her clinical history, a treatment with subcutaneous monthly administration of erenumab 70 mg was started.

Before the start of erenumab, the patient presented a clinical pattern that can be classified as chronic migraine associated with medication overuse, and she had experienced poor efficacy and tolerability of first-line drugs for prophylaxis.

Even if migraine is highly prevalent in patients with mitochondrial disorders, to date, only few reports on the treatment of this condition have been described in the literature, and a consensus guideline driving the therapeutic choices is lacking.

To explore the existing medical literature on the prophylactic treatment of migraine in mitochondrial disorders, we reviewed the literature in the Pubmed database. The last search was conducted on June 1, 2022. The search allowed to retrieve 329 papers, of which only three papers resulted to be relevant to the topic [7‐9] (Table 1). Notably, erenumab 70 mg was reported to be an effective migraine prophylaxis in a female patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS; m.3243A > G mutation) [9]. This patient had been previously treated with topiramate and onabotulinumtoxinA, which were both discontinued due to inefficacy, and flunarizine which was not tolerated due to side effects. Topiramate was reported as a treatment for migraine in another patient affected by MELAS and m.3243A > G mutation, but no data are available on its efficacy or tolerability [8]. So far, other drugs used by patients with mitochondrial disorders are propranolol, metoprolol [7], and pizotifen [8], but no information is available on their efficacy and safety. Based on the data currently available, there are no specific indications in the choice of preventive treatments in patients with genetically determined mitochondrial dysfunction, except avoiding valproic acid in the case of subjects with pathogenic variants in POLG.

Although both in the previously published case and in our patient no adverse events were reported, based on the current knowledge of the physiological actions of CGRP, we can speculate on the possible risks associated with such treatments for patients with mitochondrial disease. In particular, antibodies targeting CGRP or its receptor can interfere with the function of the small and large intestine regarding the peristaltic motor activity, the intestinal transit, and the ion and water secretion [10]. Therefore, these drugs should be administered with caution in mitochondrial patients with gastrointestinal dysfunction, frequently reported in these neurogenetic disorders [11]. At the same time, subjects with primary mitochondrial dysfunction characterized by respiratory and cardiovascular involvement should be carefully monitored during the administration of anti-CGRP‑monoclonal antibodies [12].

Our report confirms a good profile of safety and efficacy of erenumab in subjects with poor tolerability or contraindications to some prophylactic therapies, such as patients with complex comorbidities and/or diseases, including primary mitochondrial disorders.