RESUMO
BACKGROUND/AIM: The purpose of this review is to provide an overview of the contraindications, special warnings, and boxed warnings with the aim to establish a framework to create a prescription safety checklist for a class of drugs or disease indication. This study covers biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs). METHODS: We identified contraindications, boxed warnings, and special warnings provided by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The study included b/tsDMARDs approved for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), and juvenile idiopathic arthritis (JIA) within the drug-classes anti-CD20, tumor necrosis factor inhibitors (TNFi), interleukin-1 inhibitors (IL-1i), cytotoxic T-lymphocyte-associated protein (CTLA) 4, interleukin-12/23 inhibitors (IL-12/23i), interleukin 6 receptor inhibitors (IL-6Ri), Janus kinase inhibitors (JAKi), phosphodiesterase 4 inhibitors (PDE4i), interleukin-17 inhibitors (IL-17i), and interleukin-23 inhibitors (IL-23i). RESULTS: All drug classes, except PDE4i, had contraindications and/or warnings related to infections, including tuberculosis. A warning about herpes zoster was listed for anti-CD20, IL-1i, IL-6Ri, and JAKi, while a warning about hepatitis reactivation was listed for anti-CD20, TNFi, IL-1i, CTLA4-Ig, IL-6Ri, and JAKi. Malignancy risk was mentioned for all drug classes except PDE4i, IL-17i, and IL-23i. Other warnings included demyelinating disease (TNFi, CTLA4-Ig, and IL-6Ri), heart failure (anti-CD20 and TNFi), major adverse cardiac events (JAKi and IL-12/23) and venous thromboembolism (JAKi), hyperlipidemia (IL-6Ri and JAKi), liver impairment (TNFi, IL-1i, IL-6Ri, and JAKi), kidney impairment (IL-1i, JAKi, and PDE4i), inflammatory bowel disease (IL-17i), gastrointestinal perforation (IL-6Ri, JAKi), cytopenia (anti-CD20, TNFi, IL-1i, IL-6Ri, JAKi), and depression (PDE4i). Contraindications and warnings appeared to increase with the passage of time since the drug's approval. CONCLUSION: This review provides an overview to establish the framework to create an easily accessible and actionable prescription safety checklist from individual medical product prescription information provided by regulatory medical authorities.
RESUMO
The granularity and structure of the International Council for Harmonisation's (ICH) Medical Dictionary for Regulatory Activities (MedDRA) are useful for precise coding of adverse events (AEs) for data analysis. In product labeling for healthcare practitioners, however, the granularity of MedDRA Preferred Terms (PTs) can obscure the communication of adverse reactions (ARs). Driven by a focus on patient safety, business needs, and regulatory guidance, many sponsors and regulators have begun to develop institution-specific approaches to clustering similar AR terms in medical product prescribing information on a product-by-product basis. However, there are no agreed upon conventions that describe which AR terms may be appropriate to group together. In order to improve safety communication to patients and healthcare providers, there is an urgent need for a harmonized international approach to the creation and use of groups of MedDRA PTs which we refer to as "MedDRA Labeling Groupings (MLGs)" in medical product prescribing information. Given its long-standing contributions towards the design of Standardised MedDRA Queries (SMQs), the Council for International Organizations of Medical Sciences (CIOMS) convened an Expert Working Group (EWG) with involvement of multiple major stakeholders to produce a consensus document on principles and points to consider in the development of MLGs. The CIOMS MLG EWG identified variations in grouping of MedDRA PTs in product labels, and in the current document, proposes a strategy for improving the communication of drug safety labeling. It is envisaged that the use of these consensus recommendations would be voluntary and applied to product labels in a manner that is consistent with existing regulatory frameworks.
