Multiple inhaler triple therapy (MITT) is increasingly important in clinical practice, but there is little research on the clinical characteristics or previous treatment patterns of patients that follow this treatment. In addition, there is limited information in the context of real clinical practice available regarding the discontinuation of or adherence to triple therapy. To better understand which is the specific profile of asthma patients who may benefit from this treatment option, it is important to evaluate treatment patterns and clinical characteristics before the start of treatment with MITT as well as discontinuation and adherence patterns.
Objectives:
Primary:To describe the characteristics of asthma patients initiating treatment with MITT regarding demographics, comorbidities, clinical characteristics and treatment patterns during the 12 months before the index date as well as resource use during the 12 months after the index date (defined as the date of first observed prescription of all components of MITT during the study period).
Secondary:
1)To describe the discontinuation of MITT in the 12 months post-index date in terms of the number of patients discontinuing and time to discontinuation.
2)To describe the treatments established after discontinuation of MITT in patients who discontinue in the 12 months post-index date.
3)To describe patient characteristics, treatment patterns and exacerbations during the 12 months pre-index date as well as exacerbations and resource use during the 12 months post-index date, in the following groups of patients:
-Patients on MITT who do not discontinue in the 12 months post-index date (patients who remain on MITT)
-Patients who discontinue MITT within 90 days from index date
-Patients who discontinue MITT within 91-180 days from index date
-Patients who discontinue MITT within 181-365 days from index date
4)To describe patient characteristics, comorbidities as well as treatment patterns, exacerbations and resource use during the 12 months post-index date of MITT initiators patients with severe exacerbations in the 12 months pre-index date.
5)To explore treatment adherence in patients on MITT in the 12 months post-index date.
6)To estimate the prevalence rate of asthma in Catalonia.
Observational retrospective population-based study using electronic medical records from SIDIAP (System for the Development of Research in Primary Care) database. The study inclusion period will be from 1st January 2016 to 31st December 2016 (Figure 1). The index date is defined as the date of first observed prescription of all components of MITT during January 1st 2016 and December 31st 2016. Demographics, comorbidities, clinical characteristics including exacerbations and treatments patterns before MITT initiation will be collected within the 12 months pre-index date. Exacerbations, resource use and treatment patterns will be collected on the 12 months post-index date.
Initially, a descriptive analysis of the basic sociodemographic and clinical characteristics of the study population will be carried out. Adherence of asthma patients on MITT will be calculated according to the number of patients who are considered adherents in relation to the total number of patients evaluated in the 12-months post-index date. Estimate of the prevalence of asthma in Catalonia will be based on asthma patients registered in the SIDIAP database, aged 18-75, with 1 asthma medical code ICD 10-CM (previously listed).

La fibrilación auricular (FA) es la arritmia crónica más frecuente, cuya prevalencia aumenta progresivamente con la edad. Su manejo en nuestro ámbito se lleva a cabo principalmente en atención primaria y uno de sus principales objetivos es la prevención de ictus mediante el uso de anticoagulantes antagonistas de la vitamina K (AVK) o anticoagulantes orales directos (ACOD). Los ACOD han demostrado ser al menos no inferiores a AVK en la prevención de ictus en sus respectivos ensayos clínicos pivotales. Pero los resultados de estos ensayos clínicos, que suelen incluir poblaciones demasiado seleccionadas, no se pueden extrapolar a todos los pacientes y circunstancias clínicas de la práctica diaria.
Nuestro objetivo principal es analizar la efectividad y seguridad de los diferentes ACOD en comparación con los AVK para prevención de ictus en FA no valvular. Los objetivos secundarios comprenden la evaluación de eventos tromboembólicos y hemorrágicos según la persistencia a los tratamientos anticoagulantes, el sexo, la edad, la insuficiencia renal crónica, o según si los pacientes son o no naïve para tratamiento anticoagulante.
También se pretenden analizar la efectividad y seguridad de los AVK según su tiempo en rango terapéutico del INR, y la mortalidad.
Se describirán las características de aquellos pacientes con FA no valvular que no reciben ningún tratamiento antitrombótico o reciben ácido acetilsalicílico y se explorará el uso de anticoagulantes orales en pacientes con neoplasia activa, sometidos a cirugía mayor, sometidos a cardioversiones eléctricas y pacientes que hayan sufrido un infarto de miocardio.
Para ello se realizará un estudio de cohortes retrospectivo incluyendo pacientes con FA no valvular que inician tratamiento con AVK o ACOD entre noviembre 2011 y diciembre 2018.

Resum:
El uso de los inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2) se ha asociado a un mayor riesgo de presentar cetoacidosis en pacientes con diagnóstico COVID-19. Diferentes agencias de Salut el mes de abril recomendaron la no utilización de esta grupo de antidiabéticos en pacientes con diagnóstico o sospecha de COVID19.

Objetivo:
Evaluar en cuantos pacientes diabéticos tipos 2 con diagnóstico de enfermedad COVID-19 (confirmada o sospecha) se ha retirado el tratamiento con iSGLT2 durante la pandemia.Secundarios: Evaluar en cuantos pacientes se ha retirado el iSGLT2 independientemente de que tuviese diagnóstico COVID-19 o no COVID-19 (retiradas preventivas). Describir las características demográficas y clínicas y tratamientos antidiabéticos (AD) concomitantes de los pacientes a los que se ha retirado los iSGLT2 y a los que no. Diferenciar retiradas de iSGLT2 en función del diagnóstico: diabetes mellitus (DM) tipo 1, 2 o no DM. Analizar que fármacos AD se han prescrito posteriormente a la retirada del iSGLT2. Valorar si se detecta variación en el control de la enfermedad en los pacientes que se ha retirado los ISGLT2. Conocer el número de cetoacidosis registradas durante el período de la pandemia.

Metodologia:
Estudio observacional retrospectivo, a partir de la base de datos ECAP (historia clínica informatizada de Atención Primaria). Sistemas de información de la Dirección de Atención Primaría Metropolitana Nord (DAP MN) extraerá los pacientes en tratamiento con iSGLT2 de la DAP MN de manera pseudoanonimizada, durante el período abril – junio 2020.

Tots els nous hipoglucemiants no insulínics (HNI) han demostrat eficàcia en la reducció de l’HbA1c (major o menor efecte glucèmic segons el grup farmacològic) i han demostrat no associar-se a pitjors resultats de morbimortalitat CV en els estudis de seguretat CV requerits per les agències reguladores. Tot i que alguns d’aquests estudis amb ISGLT2 i ARGLP1 suggereixen que aquests fàrmacs podrien tenir beneficis en morbimortalitat CV, fins ara no està clarament establert quin és l’impacte clínic real que tenen en el tractament de la DM2 en la pràctica clínica del nostre entorn. No hi ha estudis poblacionals en el nostre entorn que hagin analitzat l’associació entre la introducció dels nous grups d’ISGLT2 i ARGLP1 i els esdeveniments clínics.
Objectiu general: estudiar l’associació entre l’evolució de la utilització dels diferents hipoglucemiants i l’evolució dels resultats en salut en la població de pacients amb DM2 de Catalunya en el període 2015-2020.
Es tracta d’un estudi observacional de disseny ecològic. A més, es durà a terme una anàlisis descriptiva dels resultats en salut en els diferents anys segons el tipus de tractament hipoglucemiant. Totes les dades provenen de fonts secundàries: fitxer de prestacions farmacèutiques del CatSalut, SIDIAP, CMBDs, RCA.
Els objectius a analitzar amb dades de SIDIAP són:
– Descriure l’evolució en el percentatge de pacients controlats (HbA1c < 7%) i de les HbA1c mitjanes en el període 2015-2020 en la població de pacients amb DM2 (amb tractament o sense) i en la població de pacients amb DM2 tractats amb hipoglucemiants. - Descriure l'evolució en el percentatge de pacients controlats (HbA1c < 7%) i de les HbA1c mitjanes en el període 2015-2020 en la població de pacients amb DM2 tractats amb hipoglucemiants en funció del tipus de tractament: HNI en monoteràpia, combinacions d'HNI, insulina en monoteràpia i combinacions d'HNI amb insulina. - Descriure l'evolució en el percentatge de pacients amb obesitat (índex de massa corporal [IMC] ? 30 Kg/m2) i de les mitjanes d'IMC en el període 2015-2020 en la població de pacients amb DM2 (amb tractament o sense) i en la població de pacients amb DM2 tractats amb hipoglucemiants. Paraules clau: diabetis mellitus tipus 2, hipoglucemiants no insulínics, evolució, mortalitat, esdeveniments cardiovasculars, HbA1c.

Rationale and background: The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of coronavirus disease 2019 (COVID-19), has led to a global pandemic. AZD1222 is a vaccine developed to prevent COVID-19. Now known as COVID-19 Vaccine AstraZeneca, the vaccine has received emergency use authorisation in the United Kingdom (UK) and conditional approval by the European Commission. Several important potential risks have been identified based on the experience of other non-COVID-19 vaccines. The clinical development programme also had limited enrolment of certain patient populations, including pregnant or breastfeeding women, individuals who are immunocompromised, frail persons with comorbidities, those with autoimmune or inflammatory disorders, and use with other vaccines such as an influenza vaccine.
Research question and objectives: What are the incidence rates (IRs) of safety events of interest (based on adverse events of special interest [AESIs]) among individuals vaccinated with AZD1222 and in individuals who have not received any vaccination for COVID-19, overall and in subpopulations of interest, within selected European data sources? How do the IRs compare with one another? What are the baseline characteristics of individuals who received at least one dose of AZD1222? How many of them received a second dose of a COVID-19 vaccine, which vaccine did they receive, and when did they receive it?
Study design: A multi-country, retrospective cohort design will be used to estimate the incidence of AESIs after receiving AZD1222 and will compare this incidence with that occurring in an unvaccinated comparator group. Where appropriate, the study will also use a self-controlled risk interval (SCRI) design. The study period will start on 04 January 2021, when the vaccine was first used in the UK, and will end approximately 24 months after it is introduced in the last country among participating data sources.
Population: The source population will comprise all individuals registered in each of the health care data sources. An exposed cohort will be identified based on first vaccination with AZD1222 (index date). A concurrent comparator population will be identified among subjects who have not received any vaccination for COVID-19 matched on the vaccinee’s index date, age, and gender.
Variables: Receipt of AZD1222, other SARS-CoV-2 vaccines, and dates of vaccination will be obtained from all possible sources that capture COVID-19 vaccination, such as pharmacy dispensing records, general practice records, and immunisation registers. Safety outcomes include safety concerns and other AESIs. These outcomes will be identified using algorithms based on codes for diagnoses, procedures, and treatments in electronic data, and they will be defined uniformly across the data sources to the fullest extent possible. Operational case definitions from the ACCESS (vACcine Covid-19 monitoring readinESS) project will be implemented for the AESIs for which they have been developed.

Background: Edoxaban is an oral anticoagulant approved in 2015 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). A European non-interventional prospective post-approval safety study (ETNA-AF study – EU-PAS register numbers EUPAS8896) is ongoing to gain insight into the safety and efficacy of edoxaban in non-preselected patients with non-valvular atrial fibrillation (NVAF) treated with edoxaban.
Objectives: The main objective of this study is to put in perspective the results of the ETNA-AF study using secondary electronic health care data and administrative health data of patients with NVAF treated with edoxaban and thus, gain additional insight into the effectiveness and safety of edoxaban in real world setting.
Methods: In this multi-country retrospective longitudinal cohort study, adult patients with NVAF initiating edoxaban will be identified in five large European databases: LHU data (Italy), GePaRD database (Germany), SIDIAP (Spain), PHARMO data (Netherlands), UK CPRD AURUM linked to HES data (UK). Observational period will be the same as in the ETNA-AF study, that is, up to 48 months after initiation of edoxaban. Primary outcomes will be occurrence of bleeding events, drug-related adverse events and mortality (all-cause, CV-related) during the observational period.
Analysis: Analysis will be purely descriptive. Baseline characteristics, primary and secondary outcomes will be analyzed for each individual database and overall, across all databases, using standard descriptive statistics. The risk of occurrence of events of interest during the observational period will be characterized using a Kaplan-Meier analysis. Country-specific results will be combined in a meta-analysis.

RIMEGEPANT (VYDURA®) HA ESTAT AUTORITZAT PER L’EMA, PERÒ A ESPANYA ENCARA NO DISPOSA DE DECISIÓ DE PREU NI FINANÇAMENT.
EL CHMP DE L’EMA VA APROVAR AQUEST PROTOCOL D’ESTUDI POST-AUTORITZACIÓ AMB ELS “TIMELINES” INDICATS AL PROTOCOL, DE MANERA QUE ENTRE EL 2on I 3er TRIMESTRE DE 2024 HEM D’ENTREGAR EL CORRESPONENT “PROGRESS REPORT.
COM QUÈ EL FÀRMAC ENCARA NO TÉ PREU NI FINANÇAMENT, PER TANT, NO ES POSSIBLE PRESCRIURE’L, EVIDENTMENT NO HI HAURÀ USUARIS DEL FÀRMAC EN EL MOMENT D’ENTREGAR EL “PROGRESS REPORT”, I NO S’HAN D’EXTRAURE DADES DE SIDIAP FINS A 2025, PERÒ PER COMPLIR AMB ELS “TIMELINES” I PODER ENTREGAR AQUEST “PROGRESS REPORT”, EL PROTOCOL D’ESTUDI HA D’ESTAR APROVAT ABANS PEL COMITÉ CIENTÍFIC DE SIDIAP I PEL CEIm.

Rationale and background: Rimegepant is a calcitonin gene–related peptide (CGRP) receptor antagonist for the treatment of acute migraine and preventive treatment of episodic migraine. The European Medicines Agency (EMA) granted approval for rimegepant in the European Union (EU) in Apr-2022 both for the acute treatment of migraine with or without aura in adults and for the preventive treatment of episodic migraine in adults who have at least 4 migraine attacks per month.
The opinion of the Committee for Medicinal Products for Human Use (CHMP) in the Day 180 review was that “Patients with cardiovascular diseases should be included as missing information. The applicant should further elaborate on this matter, taking into account the inclusion and exclusion criteria applied in the clinical trials…setting depending on the indication, and if a (theoretical) cardiac risk for Vydura exists.”
As part of the risk management plan for rimegepant in Europe, Biohaven is committed to address the request from the EMA and the Medicines and Healthcare Products Regulatory Agency (MHRA) to conduct a post-authorisation safety study (PASS) to evaluate whether there is an increased risk of major adverse cardiovascular events (MACE) among patients with migraine and history of cardiovascular disease (CVD) initiating treatment with rimegepant compared with that among patients with migraine, with history of CVD, and being treated with other treatments for migraine, either continuing the current treatment or initiating a new one, other than rimegepant. The study will also describe the use of rimegepant in the initial years after approval in the same population.

Research question and objectives: The research question is as follows: does the use of rimegepant increase the risk of MACE compared with other treatments for migraine in patients with migraine and history of CVD?
The study has 2 primary objectives:
1. To evaluate whether treatment initiation with rimegepant versus treatment with other preventive treatment for migraine (either continuing the current treatment or initiating a new one) increases the risk of MACE in patients with migraine, with history of CVD, and who are being treated with preventive migraine therapies
2. To evaluate whether treatment initiation with rimegepant versus treatment with other acute treatment for migraine (either continuing the current treatment or initiating a new one) increases the risk of MACE in patients with migraine, with history of CVD, and who are being treated with acute migraine therapies
The study has 1 secondary objective: To describe the patient characteristics of rimegepant initiators with migraine and a history of CVD (including demographics, comorbidities, comedications, and health care utilisation) at the time of rimegepant initiation and to describe their patterns of rimegepant use, including acute, preventive, or both.

Study design: This is a non-interventional population-based prospective cohort study using a prevalent new-user design. The study will be conducted in multiple data sources, comparing patients with treated migraine and a history of CVD who initiate rimegepant to comparator groups of similar patients with migraine and a history of CVD from the same data source. Both the rimegepant and comparator groups will consist of patients who have been treated with other preventive or acute treatment. This study will estimate the cumulative incidence of study outcomes with corresponding 95% confidence intervals (CIs) comparing the rimegepant initiators to the appropriate comparator group (one group of continuators or initiators of a preventive migraine medication and another group of continuators or initiators of an acute migraine medication). The analysis will be conducted separately in each data source, and overall estimates of effect will be obtained using appropriate statistical techniques. Confounding will be addressed primarily by propensity score weighting.

Population: The study population will comprise adults with migraine and history of CVD registered in each electronic health care data source who are on treatment with a qualifying acute or preventive migraine medication during the study period.
To be eligible for inclusion into the study populations, patients must have a prescription/dispensing of rimegepant or a comparator treatment for migraine within the study period, be adults (aged 18 years or older) at the index date, have at least 12 months of data available before the index date, have a diagnosis of migraine any time before or on the index date, and have a CVD diagnosis any time before or on the index date. The index date in the rimegepant groups will be defined as the date in which a patient receives a first prescription/dispensing of rimegepant within the study period and meets all the eligibility criteria. Potential index dates for the comparator groups will be defined as the date on which a patient receives a prescription/dispensing of a qualifying migraine study drug within the study period and meets all the eligibility criteria. In the analysis phase, exposure sets will be created based on the time since first prescription/dispensing of migraine medication identified in the database any time before the index date. The index date for the comparator groups will be the date of the included comparator prescriptions/dispensings within exposure sets including rimegepant index dates.
Because patients may be used as comparators for multiple rimegepant patients, a single comparator patient may have multiple comparator index dates. Furthermore, rimegepant patients may be used as comparators before their initial rimegepant prescription/dispensing.

Data sources: The study will be implemented in 4 health care data sources:
– Danish National Health Registers (DNHR) (Denmark)
– PHARMO Database Network (the Netherlands)
– Information System for the Development of Research in Primary Care (SIDIAP) (Spain)
– Clinical Practice Research Datalink (CPRD) (United Kingdom [UK])

Study size: Considering a scenario of an IR of MACE ranging between 176.1 and 210.9 per 10,000 patients and having a cohort of patients with > 1 to 5 years after migraine diagnosis, a sample size of 2,500 patients in the rimegepant group would result in a 86% or higher probability that the upper bound of the observed RR would be below 1.8.

Data analysis: Each research partner will conduct analyses separately within each data source, and results will be pooled via meta-analytic methods, if appropriate, at the end of the study. The analysis will comprise 4 different steps: select the study population, assign exposure and define follow-up, describe the study cohorts and patterns of rimegepant use, and estimate exposure propensity scores. Stabilised propensity score weights will be used in the comparative analyses, where the inverse of the propensity score is multiplied by the probability of receiving the treatment independently of baseline covariates. Crude and adjusted incidence rates of MACE with their 95% CIs will be estimated using a Poisson regression model with robust estimation of variance. Cumulative incidence of MACE will be estimated using the Kaplan-Meier estimator for each of the 4 exposure groups. Finally, for each comparison, crude and adjusted RRs and risk differences at various times during follow-up (3, 6, 9, and 12 months) will be estimated using the Kaplan-Meier estimator, and 95% CIs will be derived using bootstrap methods. Adjusted hazard ratios (HRs) will be estimated with a Cox model.

RIMEGEPANT (VYDURA®) HA ESTAT AUTORITZAT PER L’EMA, PERÒ A ESPANYA ENCARA NO DISPOSA DE DECISIÓ DE PREU NI FINANÇAMENT.
EL CHMP DE L’EMA VA APROVAR AQUEST PROTOCOL D’ESTUDI POST-AUTORITZACIÓ AMB ELS “TIMELINES” INDICATS AL PROTOCOL, DE MANERA QUE ENTRE EL 2on I 3er TRIMESTRE DE 2024 HEM D’ENTREGAR EL CORRESPONENT “PROGRESS REPORT.
COM QUÈ EL FÀRMAC ENCARA NO TÉ PREU NI FINANÇAMENT, PER TANT, NO ES POSSIBLE PRESCRIURE’L, EVIDENTMENT NO HI HAURÀ USUARIS DEL FÀRMAC EN EL MOMENT D’ENTREGAR EL “PROGRESS REPORT”, I NO S’HAN D’EXTRAURE DADES DE SIDIAP FINS A 2025, PERÒ PER COMPLIR AMB ELS “TIMELINES” I PODER ENTREGAR AQUEST “PROGRESS REPORT”, EL PROTOCOL D’ESTUDI HA D’ESTAR APROVAT ABANS PEL COMITÉ CIENTÍFIC DE SIDIAP I PEL CEIm.

Rationale and background: Rimegepant is a calcitonin gene–related peptide (CGRP) receptor antagonist for the treatment of acute migraine and preventive treatment of episodic migraine. The European Medicines Agency (EMA) granted approval for rimegepant in the European Union (EU) in Apr-2022 both for the acute treatment of migraine with or without aura in adults and for the preventive treatment of episodic migraine in adults who have at least 4 migraine attacks per month.
The opinion of the Committee for Medicinal Products for Human Use (CHMP) in the Day 180 review was that “Patients with cardiovascular diseases should be included as missing information. The applicant should further elaborate on this matter, taking into account the inclusion and exclusion criteria applied in the clinical trials…setting depending on the indication, and if a (theoretical) cardiac risk for Vydura exists.”
As part of the risk management plan for rimegepant in Europe, Biohaven is committed to address the request from the EMA and the Medicines and Healthcare Products Regulatory Agency (MHRA) to conduct a post-authorisation safety study (PASS) to evaluate whether there is an increased risk of major adverse cardiovascular events (MACE) among patients with migraine and history of cardiovascular disease (CVD) initiating treatment with rimegepant compared with that among patients with migraine, with history of CVD, and being treated with other treatments for migraine, either continuing the current treatment or initiating a new one, other than rimegepant. The study will also describe the use of rimegepant in the initial years after approval in the same population.

Research question and objectives: The research question is as follows: does the use of rimegepant increase the risk of MACE compared with other treatments for migraine in patients with migraine and history of CVD?
The study has 2 primary objectives:
1. To evaluate whether treatment initiation with rimegepant versus treatment with other preventive treatment for migraine (either continuing the current treatment or initiating a new one) increases the risk of MACE in patients with migraine, with history of CVD, and who are being treated with preventive migraine therapies
2. To evaluate whether treatment initiation with rimegepant versus treatment with other acute treatment for migraine (either continuing the current treatment or initiating a new one) increases the risk of MACE in patients with migraine, with history of CVD, and who are being treated with acute migraine therapies
The study has 1 secondary objective: To describe the patient characteristics of rimegepant initiators with migraine and a history of CVD (including demographics, comorbidities, comedications, and health care utilisation) at the time of rimegepant initiation and to describe their patterns of rimegepant use, including acute, preventive, or both.

Study design: This is a non-interventional population-based prospective cohort study using a prevalent new-user design. The study will be conducted in multiple data sources, comparing patients with treated migraine and a history of CVD who initiate rimegepant to comparator groups of similar patients with migraine and a history of CVD from the same data source. Both the rimegepant and comparator groups will consist of patients who have been treated with other preventive or acute treatment. This study will estimate the cumulative incidence of study outcomes with corresponding 95% confidence intervals (CIs) comparing the rimegepant initiators to the appropriate comparator group (one group of continuators or initiators of a preventive migraine medication and another group of continuators or initiators of an acute migraine medication). The analysis will be conducted separately in each data source, and overall estimates of effect will be obtained using appropriate statistical techniques. Confounding will be addressed primarily by propensity score weighting.

Population: The study population will comprise adults with migraine and history of CVD registered in each electronic health care data source who are on treatment with a qualifying acute or preventive migraine medication during the study period.
To be eligible for inclusion into the study populations, patients must have a prescription/dispensing of rimegepant or a comparator treatment for migraine within the study period, be adults (aged 18 years or older) at the index date, have at least 12 months of data available before the index date, have a diagnosis of migraine any time before or on the index date, and have a CVD diagnosis any time before or on the index date. The index date in the rimegepant groups will be defined as the date in which a patient receives a first prescription/dispensing of rimegepant within the study period and meets all the eligibility criteria. Potential index dates for the comparator groups will be defined as the date on which a patient receives a prescription/dispensing of a qualifying migraine study drug within the study period and meets all the eligibility criteria. In the analysis phase, exposure sets will be created based on the time since first prescription/dispensing of migraine medication identified in the database any time before the index date. The index date for the comparator groups will be the date of the included comparator prescriptions/dispensings within exposure sets including rimegepant index dates.
Because patients may be used as comparators for multiple rimegepant patients, a single comparator patient may have multiple comparator index dates. Furthermore, rimegepant patients may be used as comparators before their initial rimegepant prescription/dispensing.

Data sources: The study will be implemented in 4 health care data sources:
– Danish National Health Registers (DNHR) (Denmark)
– PHARMO Database Network (the Netherlands)
– Information System for the Development of Research in Primary Care (SIDIAP) (Spain)
– Clinical Practice Research Datalink (CPRD) (United Kingdom [UK])

Study size: Considering a scenario of an IR of MACE ranging between 176.1 and 210.9 per 10,000 patients and having a cohort of patients with > 1 to 5 years after migraine diagnosis, a sample size of 2,500 patients in the rimegepant group would result in a 86% or higher probability that the upper bound of the observed RR would be below 1.8.

Data analysis: Each research partner will conduct analyses separately within each data source, and results will be pooled via meta-analytic methods, if appropriate, at the end of the study. The analysis will comprise 4 different steps: select the study population, assign exposure and define follow-up, describe the study cohorts and patterns of rimegepant use, and estimate exposure propensity scores. Stabilised propensity score weights will be used in the comparative analyses, where the inverse of the propensity score is multiplied by the probability of receiving the treatment independently of baseline covariates. Crude and adjusted incidence rates of MACE with their 95% CIs will be estimated using a Poisson regression model with robust estimation of variance. Cumulative incidence of MACE will be estimated using the Kaplan-Meier estimator for each of the 4 exposure groups. Finally, for each comparison, crude and adjusted RRs and risk differences at various times during follow-up (3, 6, 9, and 12 months) will be estimated using the Kaplan-Meier estimator, and 95% CIs will be derived using bootstrap methods. Adjusted hazard ratios (HRs) will be estimated with a Cox model.