TY - JOUR
T1 - Methodology of the brodalumab assessment of hazards
T2 - a multicentre observational safety (BRAHMS) study
AU - Reilev, Mette
AU - Jensen, Peter Bjødstrup
AU - Ranch, Lise Skov
AU - Egeberg, Alexander
AU - Furu, Kari
AU - Gembert, Karin
AU - Hagg, David
AU - Haug, Ulrike
AU - Karlstad, Øystein
AU - Reutfors, Johan
AU - Schäfer, Wiebke
AU - Schwartz, Sarina
AU - Smits, Elisabeth
AU - Holthius, Emily
AU - Herings, Ron
AU - Trifirò, Gianluca
AU - Kirchmayer, Ursula
AU - Rosa, Alessandro Cesare
AU - Belleudi, Valeria
AU - Gini, Rosa
AU - Støvring, Henrik
AU - Hallas, Jesper
N1 - Funding Information: The study sponsor is the University of Southern Denmark, which undertakes quality assurance. The study is funded by Leo Pharma, the market authorisation holder of brodalumab, as part of an EMA mandated Post Authorisation Safety Study. Publisher Copyright: © 2023 BMJ Publishing Group. All rights reserved.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.
AB - INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.
KW - Adverse events
KW - CARDIOLOGY
KW - INFECTIOUS DISEASES
KW - ONCOLOGY
KW - Psoriasis
KW - Suicide & self-harm
UR - http://www.scopus.com/inward/record.url?scp=85147235644&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/bmjopen-2022-066057
DO - https://doi.org/10.1136/bmjopen-2022-066057
M3 - Article
C2 - 36725094
SN - 2044-6055
VL - 13
SP - e066057
JO - BMJ Open
JF - BMJ Open
IS - 2
M1 - e066057
ER -