Safety of Biologics Approved for the Treatment of Rheumatoid Arthritis and Other Autoimmune Diseases: A Disproportionality Analysis from the FDA Adverse Event Reporting System (FAERS)

Araújo, Ariane Gonçalves Silva de; Borba, Helena Hiemisch Lobo; Tonin, Fernanda S.; Lenzi, Luana; Venson, Rafael; Pontarolo, Roberto; Wiens, Astrid

doi:10.1007/s40259-018-0285-2

Cited by 12 publications

(12 citation statements)

References 64 publications

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“…Second, the spectrum of irAEs is variegate and, virtually, any organ of tissue can be involved: endocrine systems, liver, lung, gastrointestinal tract and skin, among others, thus emphasizing the importance of timely identification and early personalized management through multidisciplinary tumour board [7,8]. Notably, Individuals receiving ICIs may experience a unique set of AEs in comparison with firstand second-generation anticancer agents, including monoclonal antibodies: "traditional" biologics are associated with high frequency of reports related to general disorders/administration site condition (owing to the parenteral administration) and predictable toxicities such as infections and neoplasm due to an immune compromising effect [17][18][19][20]. From a pharmacological viewpoint, the question arises as to whether or not these irAEs are actually predictable.…”

Section: Discussionmentioning

confidence: 99%

“…FAERS is the US repository of AEs and medication errors spontaneously submitted by healthcare professionals, patients and manufacturers, gathering worldwide reports (including European reports potentially related to serious events and other non-US non-European data). In the recent past, FAERS and other spontaneous reporting systems were exploited in a number of post-marketing drug safety studies to assess both short-and long-term AEs for heterogeneous pharmacological classes [16], including biological products [17][18][19][20]. FAERS is particularly attracting among international pharmacovigilance databases because it covers a heterogeneous catchment area (allowing broader generalization of findings) and offers public access to raw data that can be downloaded in a format suitable for customized analyses [21].…”

Section: Faers: Features Acquisition and Processingmentioning

confidence: 99%

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Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System

et al. 2019

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Background Different immune-related adverse events (irAEs) were described with immune checkpoint inhibitors (ICIs), including blockers of cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death 1 or its ligand (PD1/PDL1), although their global safety is incompletely characterized.Objective To characterize spectrum, frequency and clinical features of ICI-related adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS). Patients and MethodsAEs from FAERS (up to June 2018) recording ICIs (ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab) as suspect were extracted. Comprehensive disproportionality analyses were performed through the reporting odds ratio (ROR) with 95% confidence interval (95%CI), using other oncological drugs as comparison. An overview of systematic reviews (OoSRs) was also undertaken to identify irAEs with consistent positive associations. ResultsICIs were recorded in 47,266 reports, submitted mainly by consumers receiving monotherapy with anti-PD1/PDL1 drugs. Three areas of toxicity emerged from both disproportionality and OoSRs (33 studies):

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Section: Discussionmentioning

confidence: 99%

Section: Faers: Features Acquisition and Processingmentioning

confidence: 99%

Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System

et al. 2019

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“…However, FAERS is wellvalidated for toxicity evaluations across many cancer and non-cancer drugs. [11][12][13][14]17,18,[43][44][45] Also, reporting is mandatory for manufacturers, but voluntary for physicians and patients; thus, the extent of AEs in our study may be underreported. 46 Despite this, we found signals for general health deterioration, bone pain, and hematologic AEs.…”

Section: Fda Reported Adverse Events For Radium-223mentioning

confidence: 95%

Adverse Events Associated With Radium-223 in Metastatic Prostate Cancer: Disproportionality Analysis of FDA Data Reflecting Worldwide Utilization

Huynh‐Le

Shults

Connor

et al. 2020

Clinical Genitourinary Cancer

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Radium-223 improves overall survival in metastatic castrate-resistant prostate cancer, but real-time international utilization is unknown. We used United States Food and Drug Administration data to identify adverse events associated with radium-223, including health deterioration, bone pain, and hematologic toxicities. Patients with metastatic castrate-resistant prostate cancer experiencing toxicity are only receiving one-half the radium-223 prescription dose. These real-world data are critical for risk-benefit assessments of radium-223 use. Background: Radionuclide radium-223 improves survival in men with metastatic castrate-resistant prostate cancer. The United States (US) Food and Drug Administration Adverse Events Reporting System (FAERS) is a post-market pharmacovigilance database valuable for adverse event (AE) assessments. We analyzed FAERS to identify disproportionate AE signals related to radium-223, and to explore radium-223's international utilization. Materials and Methods: We identified 2182 radium-223 cases associated with AE(s) from 2013 to 2018. The duration of radium-223 therapy was calculated. Reporting odds ratio (ROR) and proportional reporting ratio (PRR), with 95% confidence intervals (CIs), were calculated for AEs of interest. ROR shows disproportionate signals if the lower limit of the 95% CI > 1. PRR shows disproportionate signals if PRR ! 2, c 2 statistic ! 4, and ! 3 AEs were reported. We identified any US Food and Drug Administration enforcement actions for radium-223. Results: A majority (60.8%) of events occurred outside the US. Among patients with radium-223-associated AEs, the median therapy duration was only 56 days (corresponding to 2-3 treatment cycles). Disproportionate signals were detected for general health deterioration (ROR,

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“…In the COVID-19 era, pharmacovigilance plays a crucial role for real-time safety monitoring of pharmaceuticals: the global vaccination campaign exemplifies the importance of post-marketing studies for timely detection of rare but serious AEs such as myocarditis, thrombocytopenia, and cerebral venous sinus thrombosis, which may not be fully appreciated in the pre-marketing setting, especially for medications receiving accelerated conditional approval through the so-called rolling review [ 44 ]. In particular, spontaneous reporting databases, such as the FDA Adverse Event Reporting System (FAERS) and WHO-Vigibase, have been successfully exploited to characterize the safety profile of drugs, thus informing clinical practice for proactive monitoring [ 45 , 46 ].…”

Section: Safety Issuesmentioning

confidence: 99%

Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues

et al. 2021

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We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID-19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID-19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered.

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Safety of Biologics Approved for the Treatment of Rheumatoid Arthritis and Other Autoimmune Diseases: A Disproportionality Analysis from the FDA Adverse Event Reporting System (FAERS)

Cited by 12 publications

References 64 publications

Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System

Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System

Adverse Events Associated With Radium-223 in Metastatic Prostate Cancer: Disproportionality Analysis of FDA Data Reflecting Worldwide Utilization

Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues

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