Combination of anti-CGRP/CGRP-R mAbs with onabotulinumtoxin A as a novel therapeutic approach for refractory chronic migraine: a retrospective study of real-world clinical evidence and a protocol for a double-blind, randomized clinical trial to establish the efficacy and safety.

Chronic migraine is a disabling neurovascular disorder that ranks amongst the top causes of years lived with disability worldwide. The duration and the frequency of migraine affect cognitive and affective domains, inducing worsening of memory, executive functions, orientation and causing anxiety. Population-based studies report a worrying level of resistance to treatments. Therefore, this study aims: 1) to assess efficacy of monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) or its receptor (CGRP-R) for chronic migraine resistant to current preventatives; 2) to design a clinical trial protocol to evaluate the efficacy and safety of combination therapy utilizing anti-CGRP/CGRP-R together with onabotulinumtoxin A in patients suffering from resistant chronic migraine; 3) to provide a molecular rationale for combination therapy. A controlled trial is warranted as pooled analysis of real-world data from our group highlighted that combined treatment provides ≥50% reduction vs. baseline (onabotulinumtoxin A) of monthly headache days (MHDs) in up to 58.8% of patients, but there has been only sparse application of this combined therapy to date. The mAbs chosen are: erenumab, because its combination effect with onabotulinumtoxin A improved symptoms in 65% of patients; eptinezumab, due to its faster action. The results highlight that early diagnosis of migraine improves therapeutic outcomes with mAbs alone, confirming their effectiveness and the need for an adequately powered clinical trial evaluating the safety and potential superior effectiveness of eptinezumab/erenumab and onabotulinumtoxin A together.

Poor patient awareness and frequent misdiagnosis of migraine: findings from a large transcontinental cohort.

BACKGROUND AND PURPOSE: Although migraine is the second most disabling condition worldwide, there is poor awareness of it. The objective was to assess the awareness of migraine and previous diagnostic and therapeutic consultations and treatments in a large international population of migraineurs. METHODS: This was a multicentre study conducted in 12 headache centres in seven countries. Each centre recruited up to 100 patients referred for a first visit and diagnosed with migraine. Subjects were given a structured clinical questionnaire-based interview about the perceptions of the type of headache they suffered from, its cause, previous diagnoses, investigations and treatments. RESULTS: In all, 1161 patients completed the study. Twenty-eight per cent of participants were aware that they suffered from migraine. Sixty-four per cent called their migraine 'headache'; less commonly they used terms such as 'cervical pain' (4%), tension headache (3%) and sinusitis (1%). Eight per cent of general practitioners and 35% of specialists (of whom 51% were neurologists and/or headache specialists) consulted for migraine formulated the correct diagnosis. Before participating in the study, 50% of patients had undergone X-ray, computed tomography and/or magnetic resonance imaging of the cervical spine and 76% underwent brain and/or cervical spine imaging for migraine. Twenty-eight per cent of patients had received symptomatic migraine-specific medications and 29% at least one migraine preventive medication. CONCLUSIONS: Although migraine is a very common disease, poor awareness of it amongst patients and physicians is still an issue in several countries. This highlights the importance of the promotion of migraine awareness to reduce its burden and limit direct and indirect costs and the risk of exposure to useless investigations.

Relationship between high prolactin levels and migraine attacks in patients with microprolactinoma.

The pathophysiology of pituitary-associated headache is unknown, although structural and functional features of the tumour are proposed mechanisms. The objective of this study was to evaluate whether headache in a population with pituitary micro-adenomas was related to hyperprolactinemia. We recruited 29 patients with microprolactinoma and headache: 16 with migraine (group A) and 13 with tension-type-headache (group B). The prolactin (PRL) levels measured during attacks of headache were significantly higher in nine patients (56%) of group A and in one patient (8%) of group B. In four of the nine patients of group A, PRL increased after thyrotropin-releasing-hormone (TRH) test and induced severe attacks. After dopamine-agonist (DA) treatment, the headache improved in seven (44%) patients of the group A and in two (15%) patients of the group B. Three of the four patients in whom the TRH-test induced headache attacks, improved after DA treatment. We suggest that hyperprolactinemia may contribute to development of pain in migraine subgroups and further TRH-test could be used to predict which patients could benefit by DA therapy.

Evidence-based medicine and headache patient management by general practitioners in Italy.

The study explores the awareness of technical terms used in evidence-based medicine (EBM) and manner of treating patients with migraine among a random sample of 500 general practitioners (GPs). A mailed questionnaire included questions on GPs' demographics and practice characteristics; awareness of EBM; sources of information about migraine and EBM; and patient's treatment behaviour. Only 27.2% of GPs agreed that clinical trials are needed to evaluate the efficacy of treatments and this awareness was higher in those who learned about migraine from scientific journals or continuing education courses and who attended courses on EBM. For two-thirds of GPs, disability is equivalent to illness diagnosis, and this behaviour was more prevalent in those who agreed that clinical trials are needed to evaluate the efficacy of preventive or curative treatments of migraine and that the clinical approach to migraine required an evaluation of clinical effectiveness, in those who treated a lower number of headache patients, who were older, and in those who did not use guidelines. The majority (93.1%) of GPs indicated that it is important to integrate clinical practice and the best available evidence, and this behaviour was significantly more frequent in those who agreed that the clinical approach to migraine required a clinical effectiveness evaluation, that clinical trials are needed to evaluate the efficacy of preventive or curative treatments of migraine, and in those who attended courses on EBM. Training and continuing educational programmes on EBM and guidelines on treatments of headache for GPs are strongly needed.

Dynamic evaluation by TV-pupillometry of the mydriatic effect of ibopamine solution. Controlled studies.

The aim of the study was to evaluate in man the dose-effect relationship of ibopamine solution 0.25%, 0.50% and 1% on the pupillary diameter and the pupillary reflex to light stimulus and near vision. A cross-over study was performed in comparison with a placebo and with tropicamide solution 1% in 18 healthy volunteers. The results show that ibopamine 1% determines a marked mydriatic effect. At the doses used, it produces a maximum increase of the pupillary diameter with a dose-effect relationship which does not depart significantly from a straight line. The maximum mydriatic effect of ibopamine 1% is significantly greater than that of tropicamide 1%. The mydriatic effect of ibopamine lasts for about 3 h; that of tropicamide lasts longer. Tropicamide 1% markedly and for a long period inhibits the pupillary reflex both to light and to near vision. The effect of ibopamine 1% on the pupillary reflex to near vision is slight, while on the reflex to light stimulus it is essentially comparable to that of tropicamide.