2019年疼痛防治和痛觉机制十大研究突破

1.N Engl J Med+Lancet— 人源化抗CGRP抗体或者CGRP阻断剂防治偏头痛取得较好疗效

英文摘:1：

BACKGROUND:

Antibodiestargeting calcitonin gene-related peptide (CGRP) or its receptor have shownefficacy in the prevention of migraine attacks. We investigated the efficacyand tolerability of fremanezumab, a fully humanised CGRP antibody, in patientswith migraine who had previously not responded to two to four classes ofmigraine preventive medications.

METHODS:

Therandomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUStrial was done at 104 sites (including hospitals, medical centres, researchinstitutes, and group practice clinics) across Belgium, the Czech Republic,Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain,Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18-70years with episodic or chronic migraine who had documented failure to two tofour classes of migraine preventive medications in the past 10 years. Failurewas defined as no clinically meaningful improvement after at least 3 months oftherapy at a stable dose, as per the treating physician's judgment;discontinuation because of adverse events that made treatment intolerable; ortreatment contraindicated or unsuitable for the preventive treatment ofmigraine for the patient. Participants were randomly assigned (1:1:1) byelectronic interactive response technology to subcutaneously administeredquarterly fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthlyfremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronicmigraine; months 2 and 3: 225 mg in both migraine subgroups), or matchedmonthly placebo for 12 weeks. The primary outcome was mean change from baselinein the monthly average number of migraine days during the 12-week treatmentperiod. This trial is registered with ClinicalTrials.gov, number NCT03308968,and is now completed.

FINDINGS:

BetweenNov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) orchronic (509 [61%]) migraine were randomly assigned to placebo (n=279),quarterly fremanezumab (n=276), or monthly fremanezumab (n=283). Reductionsfrom baseline in monthly average migraine days over 12 weeks were greaterversus placebo (least-squares mean [LSM] change -0·6 [SE 0·3]) with quarterlyfremanezumab (LSM change -3·7 [0·3]; LSM difference vs placebo -3·1 [95% CI-3·8 to -2·4]; p<0·0001) and with monthly fremanezumab (LSM change -4·1[0·34]; LSM difference vs placebo -3·5 [-4·2 to -2·8]; p<0·0001). Adverseevents were similar for placebo and fremanezumab. Serious adverse events werereported in four (1%) of 277 participants with placebo, two (<1%) of 276with quarterly fremanezumab, and four (1%) of 285 with monthly fremanezumab.

INTERPRETATION:

Fremanezumabwas effective and well tolerated in patients with difficult-to-treat migrainewho had previously not responded to up to four classes of migraine preventivemedications.

英文摘要2：

BACKGROUND:

Rimegepant,a small molecule calcitonin gene-related peptide receptor antagonist, has shownefficacy in the acute treatment of migraine using a standard tabletformulation. The objective of this trial was to compare the efficacy, safety,and tolerability of a novel orally disintegrating tablet formulation ofrimegepant at 75 mg with placebo in the acute treatment of migraine.

METHODS:

Inthis double-blind, randomised, placebo-controlled, multicentre phase 3 trial,adults aged 18 years or older with history of migraine of at least 1 year wererecruited to 69 study centres in the USA. Participants were randomly assignedto receive rimegepant (75 mg orally disintegrating tablet) or placebo andinstructed to treat a single migraine attack of moderate or severe painintensity. The randomisation was stratified by the use of prophylacticmedication (yes or no), and was carried out using an interactive web responsesystem that was accessed by each clinical site. All participants,investigators, and the sponsor were masked to treatment group assignment. Thecoprimary endpoints were freedom from pain and freedom from the most bothersomesymptom at 2 h postdose. The efficacy analyses used the modifiedintention-to-treat population, which included all patients who were randomlyassigned, had a migraine attack with pain of moderate or severe intensity, tooka dose of rimegepant or placebo, and had at least one efficacy assessment afteradministration of the dose. The safety analyses included all randomly assignedparticipants who received at least one dose of study medication. This study isregistered with ClinicalTrials.gov, number NCT03461757, and is closed toaccrual.

FINDINGS: