- Klíčová slova
- studie APPRAISE, erenumab,
- MeSH
- antagonisté CGRP receptorů farmakologie terapeutické užití MeSH
- humanizované monoklonální protilátky farmakologie terapeutické užití MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- migréna * farmakoterapie prevence a kontrola MeSH
- peptid spojený s genem pro kalcitonin antagonisté a inhibitory terapeutické užití MeSH
- Check Tag
- lidé MeSH
Migréna je záchvatovité neurologické onemocnění s výrazným dopadem na kvalitu života pacientů. Prevalence migrény se celosvětově pohybuje kolem 17 % u žen a 6 % u mužů, nejčastěji se vyskytuje mezi 30. a 40. rokem života. Migréna je druhou nejčastější příčinou disability po vertebrogenních onemocněních a třetí nejčastější neurologické onemocnění vůbec. Představuje tak pro společnost významnou ekonomickou zátěž, proto potřebujeme co nejdokonalejší a nejúčinnější terapii. V posledních třech letech máme již takovou léčbu k dispozici ve formě monoklonálních protilátek.
Migraine is an attack-like neurological disease with a significant impact on patients' quality of life. The prevalence of migraine worldwide is around 17% in women and 6% in men, with the most frequent occurrence between 30 and 40 years of age. Migraine is the second most common cause of disability after vertebrogenic disorders and the third most common neurological disorder overall. It represents a significant economic burden on society, which is why we need the most sophisticated and effective therapies. In the last three years, we already have such a treatment available in the form of monoclonal antibodies.
- MeSH
- biologická terapie MeSH
- humanizované monoklonální protilátky farmakologie terapeutické užití MeSH
- lidé MeSH
- migréna bez aury diagnóza MeSH
- migréna s aurou diagnóza MeSH
- migréna * diagnóza farmakoterapie prevence a kontrola MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- tryptaminy farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- fremanezumab,
- MeSH
- humanizované monoklonální protilátky aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- migréna * ekonomika farmakoterapie prevence a kontrola psychologie MeSH
- multicentrické studie jako téma MeSH
- peptid spojený s genem pro kalcitonin antagonisté a inhibitory MeSH
- prevalence MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- fremanezumab, studie PEARL,
- MeSH
- humanizované monoklonální protilátky farmakologie terapeutické užití MeSH
- klinické zkoušky, fáze IV jako téma metody MeSH
- lidé MeSH
- migréna * farmakoterapie prevence a kontrola MeSH
- peptid spojený s genem pro kalcitonin antagonisté a inhibitory MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- fremanezumab,
- MeSH
- antagonisté CGRP receptorů * farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- migréna * farmakoterapie patofyziologie prevence a kontrola MeSH
- sekundární bolesti hlavy etiologie MeSH
- senioři MeSH
- výchova a vzdělávání MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- zprávy MeSH
IMPORTANCE: Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden. OBJECTIVE: To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments. DESIGN, SETTING, AND PARTICIPANTS: The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021. This pragmatic trial was conducted at 84 centers across 17 countries. Overall, participants 18 years or older with a 12-month or longer history of migraine, and 4 or more but fewer than 15 monthly migraine days (MMDs) were included. INTERVENTIONS: Patients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent). MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients completing 1 year of the initially assigned treatment and achieving a reduction of 50% or greater from baseline in MMDs at month 12. Secondary end points included the cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders according to the Patients' Global Impression of Change (PGIC) scale at month 12 for patients taking the initially assigned treatment. RESULTS: A total of 866 patients were screened, of whom 245 failed the screening and 621 completed the screening and baseline period. Of the 621 randomized patients (mean [SD] age, 41.3 [11.2] years; 545 female [87.8%]; 413 [66.5%] in the erenumab group; 208 [33.5%] in the OMPM group), 523 (84.2%) completed the treatment phase, and 98 (15.8%) discontinued the study. At month 12, significantly more patients assigned to erenumab vs OMPM achieved the primary end point (232 of 413 [56.2%] vs 35 of 208 [16.8%]; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). Compared with OMPMs, treatment with erenumab showed higher responder rate (314 of 413 [76.0%] vs 39 of 208 [18.8%]; OR, 13.75; 95% CI, 9.08-20.83; P <.001) on the PGIC scale (≥5 at month 12). Significant reduction in cumulative average MMDs was reported with erenumab treatment vs OMPM treatment (-4.32 vs -2.65; treatment difference [SE]: -1.67 [0.35] days; P < .001). Substantially fewer patients in the erenumab arm compared with the OMPM arm switched medication (9 of 413 [2.2%] vs 72 of 208 [34.6%]) and discontinued treatment due to adverse events (12 of 408 [2.9%] vs 48 of 206 [23.3%]). No new safety signals were identified. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial demonstrated that earlier use of erenumab in patients with EM who failed 1 or 2 previous preventive treatments provided greater and sustained efficacy, safety, and adherence than continuous OMPM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03927144.
- MeSH
- adherence k farmakoterapii MeSH
- antagonisté CGRP receptorů aplikace a dávkování terapeutické užití MeSH
- aplikace orální MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- migréna * farmakoterapie prevence a kontrola MeSH
- prospektivní studie MeSH
- spokojenost pacientů MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze IV MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has been approved for the preventive treatment of migraine, but its efficacy and safety in people who have been failed by conventional oral preventive migraine treatments has not yet been evaluated in a dedicated clinical trial. The ELEVATE trial evaluated the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in participants for whom two to four classes of conventional oral preventive treatments have failed. METHODS: ELEVATE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3b trial done at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the UK, and the USA. Adults (18-80 years) with episodic migraine who had previously been failed by two to four classes of conventional oral treatments for migraine prevention were randomly assigned (1:1) using interactive web response technology to oral atogepant 60 mg once a day or placebo, stratified by baseline monthly migraine days, number of treatment classes participants have been failed by, and region. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the off-treatment hypothetical estimand (OTHE) population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods (whether on treatment or off treatment). The primary endpoint was analysed using a mixed model for repeated measures and a fixed-sequence procedure was used to control for multiple comparisons. The trial is registered with ClinicalTrials.gov (NCT04740827) and EudraCT (2019-003448-58), and is completed. FINDINGS: Between March 5, 2021, and Aug 4, 2022, 540 participants were screened, 315 were randomly assigned, and 313 participants (280 [89%] female, 33 [11%] male, and 300 [96%] White) received at least one dose of study intervention. In the OTHE population, which comprised 309 participants (155 assigned to placebo and 154 to atogepant), least squares mean changes from baseline in monthly migraine days across 12 weeks were -1·9 (SE 0·4) with placebo and -4·2 (0·4) with atogepant (least squares mean difference -2·4, 95% CI -3·2 to -1·5; adjusted p<0·0001). The most common treatment-emergent adverse event with atogepant was constipation in 16 (10%) of 156 participants (vs four [3%] of 157 for placebo). Serious adverse events occurred in four [3%] of 156 participants in the atogepant group vs none in the placebo group, and treatment-emergent adverse events resulting in treatment discontinuation occurred in three [2%] in the atogepant group vs two [1%] in the placebo group. INTERPRETATION: Atogepant 60 mg once a day was safe, well tolerated, and showed significant and clinically relevant reductions in mean monthly migraine days compared with placebo across 12 weeks in patients with episodic migraine who had previously been failed by two to four classes of conventional oral preventive treatments. Atogepant might be an effective preventive treatment option for patients in this difficult-to-treat population. FUNDING: Allergan (now AbbVie).
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- lidé MeSH
- migréna * farmakoterapie prevence a kontrola MeSH
- monoklonální protilátky * terapeutické užití MeSH
- piperidiny * MeSH
- pyridiny * MeSH
- pyrroly * MeSH
- spirosloučeniny * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
- MeSH
- antagonisté CGRP receptorů aplikace a dávkování farmakologie klasifikace MeSH
- biologická terapie metody MeSH
- látky ovlivňující centrální nervový systém * klasifikace terapeutické užití MeSH
- lidé MeSH
- migréna * farmakoterapie prevence a kontrola MeSH
- peptid spojený s genem pro kalcitonin antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
