Few studies have directly compared the clinical features of neuropathic and non-neuropathic pains. For this purpose, the French Neuropathic Pain Group developed a clinician-administered questionnaire named DN4 consisting of both sensory descriptors and signs related to bedside sensory examination. This questionnaire was used in a prospective study of 160 patients presenting with pain associated with a definite neurological or somatic lesion. The most common aetiologies of nervous lesions (n=89) were traumatic nerve injury, post herpetic neuralgia and post stroke pain. Non-neurological lesions (n=71) were represented by osteoarthritis, inflammatory arthropathies and mechanical low back pain. Each patient was seen independently by two experts in order to confirm the diagnosis of neuropathic or non-neuropathic pain. The prevalence of pain descriptors and sensory dysfunctions were systematically compared in the two groups of patients. The analysis of the psychometric properties of the DN4 questionnaire included: face validity, inter-rater reliability, factor analysis and logistic regression to identify the discriminant properties of items or combinations of items for the diagnosis of neuropathic pain. We found that a relatively small number of items are sufficient to discriminate neuropathic pain. The 10-item questionnaire developed in the present study constitutes a new diagnostic instrument, which might be helpful both in clinical research and daily practice.

This large national population-based study indicates that a significant proportion of chronic pain patients report neuropathic characteristics. We identified distinctive sociodemographic profile and clinical features indicating that chronic pain with neuropathic characteristics is a specific health problem.

This study describes the development and validation of the Neuropathic Pain Symptom Inventory (NPSI), a new self-questionnaire specifically designed to evaluate the different symptoms of neuropathic pain. Following a development phase and a pilot study, we generated a list of descriptors reflecting spontaneous ongoing or paroxysmal pain, evoked pain (i.e. mechanical and thermal allodynia/hyperalgesia) and dysesthesia/paresthesia. Each of these items was quantified on a (0-10) numerical scale. The validation procedure was performed in 176 consecutive patients with neuropathic pain of peripheral (n = 120) or central (n = 56) origin, recruited in five pain centers in France and Belgium. It included: (i) assessment of the test-retest reliability of each item, (ii) determination of the factorial structure of the questionnaire and analysis of convergent and divergent validities (i.e. construct validity), and (iii) evaluation of the ability of the NPSI to detect the effects of treatment (i.e. sensitivity to change). The final version of the NPSI includes 10 descriptors (plus two temporal items) that allow discrimination and quantification of five distinct clinically relevant dimensions of neuropathic pain syndromes and that are sensitive to treatment. The psychometric properties of the NPSI suggest that it might be used to characterize subgroups of neuropathic pain patients and verify whether they respond differentially to various pharmacological agents or other therapeutic interventions.

Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology. Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention. Methods In this randomized, double-blind, placebo-controlled, phase 3 study, 577 adults with episodic migraine were randomized to placebo or 70 mg erenumab; 570 patients were included in efficacy analyses. Primary endpoint was change in monthly migraine days. Secondary endpoints were ≥50% reduction in monthly migraine days, change in acute migraine-specific medication treatment days, and ≥5-point reduction in Physical Impairment and Impact on Everyday Activities domain scores measured by the Migraine Physical Function Impact Diary. All endpoints assessed change from baseline at month 3. Results Patients receiving erenumab experienced -2.9 days change in monthly migraine days, compared with -1.8 days for placebo, least-squares mean (95% CI) treatment difference of -1.0 (-1.6, -0.5) ( p < 0.001). A ≥ 50% reduction in monthly migraine days was achieved by 39.7% (erenumab) and 29.5% (placebo) of patients (OR:1.59 (95% CI: 1.12, 2.27) ( p = 0.010). Migraine-specific medication treatment days were reduced by -1.2 (erenumab) and -0.6 (placebo) days, a treatment difference of -0.6 (-1.0, -0.2) ( p = 0.002). The ≥5-point reduction rates in Migraine Physical Function Impact Diary - Physical Impairment were 33.0% and 27.1% (OR:1.33 (0.92, 1.90) ( p = 0.13) and in Migraine Physical Function Impact Diary - Everyday Activities were 40.4% and 35.8% (OR:1.22 (0.87, 1.71) ( p = 0.26). Safety and adverse event profiles of erenumab were similar to placebo. Most frequent adverse events were upper respiratory tract infection, injection site pain, and nasopharyngitis. Conclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use. (Funded by Amgen). Trial registration ClinicalTrials.gov, NCT02483585.

Headache disorders are prominent health-related drivers of immense economic losses for the EU. This has immediate implications for healthcare policy. Health care for headache can be both improved and cost saving.

Klatt, J. (2018). Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet.Abstract: 299 words excluding Current word count: 4621 (including Research in 24 context) 25 Manuscript LIBERTY-primary manuscript Re-submission draft 2 Summary 26Background: A significant proportion of patients does not respond to, or cannot tolerate, current 27 oral migraine preventives. Erenumab is a novel CGRP-receptor antibody with preventive 28 efficacy in migraine. Here we assessed its efficacy and tolerability in patients with episodic 29 migraine who had previously failed 2-4 migraine preventives (efficacy failure: no meaningful 30 reduction in headache frequency after administration of approved preventive for migraine for at 31 least 2-3 months based on patient history and medical judgment). 32Methods: LIBERTY (NCT03096834) was a 12-week, double-blind, randomised study. 33Participants with migraine symptoms from 4-14 days/month (28-day interval) across the three 34 months prior to screening and during the baseline period were randomised (1:1) to receive 35 erenumab 140 mg or placebo every four weeks subcutaneously for the 12-week double-blind 36 treatment phase. The primary endpoint was proportion of patients achieving ≥50% reduction in 37 monthly migraine days during Weeks 9-12. Additionally, safety and tolerability were also 38 assessed by recording adverse events and by physical examination, vital signs, clinical laboratory 39 assessments, and electrocardiogram. 40 Findings: Of 246 randomised participants (n=121 for erenumab 140 mg and n=125 for placebo), 41 240 completed the double-blind phase. Of these, 95 (38·6%), 93 (37·8%), and 56 (22·8%) had 42 previously failed two, three, and four preventives, respectively. At Week 12, the ≥50% responder 43 rate was observed in 36 (30·3%) patients on erenumab versus 17 (13·7%) patients on placebo 44 (odds ratio, 95% confidence interval [CI]: 2·7 [1·4, 5·2]; p=0·002). The tolerability and safety 45 profiles of erenumab were comparable to placebo. The most frequent treatment-emergent 46 adverse events was injection site pain (7 [5.9%] with erenumab 140 mg, 7 [5.6%] placebo).47 Interpretation: Erenumab was effective in patients with episodic migraine who previously did 48 not respond to/tolerate 2-4 migraine preventives. Erenumab might be an option for patients with 49 difficult-to-treat migraine who have high unmet needs and limited treatment options.50 Funding: Novartis Pharma AG 51 52 LIBERTY-primary manuscript Re-submission draft 3 Research in context 53Evidence before this study 54 We searched PubMed to identify articles published in English language between January 1, 55 2010, and June 18, 2018, using the search terms "episodic migraine", "CGRP OR calcitonin 56 gene-related peptide", and "antibody OR antibodies". The search retrieved 38 articles. Published 57 literature suggests that CGRP is involved in the pathophysiology...

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BackgroundEuropean data, at least from Western Europe, are relatively good on migraine prevalence but less sound for tension-type headache (TTH) and medication-overuse headache (MOH). Evidence on impact of headache disorders is very limited. Eurolight was a data-gathering exercise primarily to inform health policy in the European Union (EU). This manuscript reports personal impact.MethodsThe study was cross-sectional with modified cluster sampling. Surveys were conducted by structured questionnaire, including diagnostic questions based on ICHD-II and various measures of impact, and are reported from Austria, France, Germany, Italy, Lithuania, Luxembourg, Netherlands, Spain and United Kingdom. Different methods of sampling were used in each. The full methodology is described elsewhere.ResultsQuestionnaires were analysed from 8,271 participants (58% female, mean age 43.4 y). Participation-rates, where calculable, varied from 10.6% to 58.8%. Moderate interest-bias was detected. Unadjusted lifetime prevalence of any headache was 91.3%. Gender-adjusted 1-year prevalences were: any headache 78.6%; migraine 35.3%; TTH 38.2%, headache on ≥15 d/mo 7.2%; probable MOH 3.1%. Personal impact was high, and included ictal symptom burden, interictal burden, cumulative burden and impact on others (partners and children). There was a general gradient of probable MOH > migraine > TTH, and most measures indicated higher impact among females. Lost useful time was substantial: 17.7% of males and 28.0% of females with migraine lost >10% of days; 44.7% of males and 53.7% of females with probable MOH lost >20%.ConclusionsThe common headache disorders have very high personal impact in the EU, with important implications for health policy.