Pharmacovigilance Assessment of Immune‐Mediated Reactions Reported for Checkpoint Inhibitor Cancer Immunotherapies

Ali, Ayad; Watson, David E.

doi:10.1002/phar.2035

Cited by 33 publications

(20 citation statements)

References 24 publications

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“…There is only one pharmacovigilance study generally described ICIs-mediated reactions in different organs, including the kidney. 18 Knowledge is scarce about the detailed safety profile of renal adverse effects following various ICIs in real-world clinical practice. Therefore, we aimed to evaluate and compare the links between different ICIs and renal adverse effects in a large population by investigating the FDA's Adverse Event Reporting System (FAERS) until recently.…”

Section: Introductionmentioning

confidence: 99%

Renal adverse effects following the use of different immune checkpoint inhibitor regimens: A real‐world pharmacoepidemiology study of post‐marketing surveillance data

et al. 2020

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Backgrounds Although kidney impairments have been reported following immune checkpoint inhibitors (ICIs) in clinical studies, there are few pharmacoepidemiology studies to compare the occurrences, clinical features, and prognosis of renal adverse effects. Methods Disproportionality and Bayesian analysis were used in data mining to screen the suspected renal adverse effects after the administration of different ICIs, based on FDA's Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset, fatality and hospitalization rates of renal adverse effects were also investigated. Results We identified 1444 reports of renal adverse effects. Affected patients tended to be older than 65 years (52.7%). Renal effects were most commonly reported in nivolumab monotherapy (33.24%). Atezolizumab appeared the strongest association among six ICI monotherapies, based on the highest reporting odds ratio (ROR = 144.38, two‐sided 95% CI = 123.08 −169.37), proportional reporting ratio (PRR = 139.13, χ2 = 21 425.38), and empirical Bayes geometric mean (EBGM = 131.75, one‐sided 95% CI = 115.28). The combination treatments showed higher RORs, PRRs, and EBGMs, compared with either nivolumab or pembrolizumab monotherapy. The median onset time of renal adverse effects was 48 (interquartile range [IQR] 18.75‐121.25) days after the monotherapies of ICI regimens. Patients treated with the combination of nivolumab plus ipilimumab were younger than receivers in nivolumab monotherapy (63.81 ± 12.03 vs 66.39 ± 11.53, P = .004); The fatality rate of renal adverse effects appeared lower in the combination group, compared to nivolumab monotherapy (18.53% vs 27.50%, P = .004). The top hospitalization rates due to renal effects occurred in patients with combination therapies. Conclusion Based on the FAERS database, we profiled renal adverse effects after various ICIs with real‐world data in occurrences, clinical characteristics, and prognosis. Renal effects should be tightly monitored, especially within the first several months after ICIs administration. Particular concern should be paid for patients with a tendency for kidney impairments, such as old age.

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Section: Introductionmentioning

confidence: 99%

Renal adverse effects following the use of different immune checkpoint inhibitor regimens: A real‐world pharmacoepidemiology study of post‐marketing surveillance data

et al. 2020

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“…The management of ADR reports is largely medicalized and data standardized according to the Medical Dictionary for Regulatory Activities (MedDRA) [29]. In oncology, some ADR associated with new drugs have been investigated using various pharmacovigilance databases including the French BNPV [33–40].…”

Section: Medical Record Databasesmentioning

confidence: 99%

Overview of French databases available for studying anticancer drugs in real‐life setting

Casarotto

Noïze

Gouverneur

et al. 2020

Fundamemntal Clinical Pharma

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Considering their novelty and cost, post‐marketing evaluation is highly relevant for new anticancer drugs. Identify and characterize available and potentially useful databases for post‐marketing evaluation of these specific drugs is necessary. A review was conducted to identify available and accessible databases to study the post‐marketing evaluation of drugs in real‐life care setting. Databases identified have been classified into medico‐administrative databases, medical record databases, and databases resulting from ad hoc collections. Taking as examples databases available in France, each type was described as well as its strengths and limits for a potential use in the oncology field. Record linkage of medico‐administrative databases could cover almost the whole population and is now used to evaluate anticancer drugs (e.g., Système National des Données de Santé). Large medical record databases are still lacking, but efforts are currently made to give access to hospital data warehouses for research purposes. Finally, databases resulting from ad hoc collections are also available for some cancer localizations and allow to obtain highly valuable clinical and biological data. A range of important and valuable databases exist but, individually, none is enough to answer to all questions from health authorities, healthcare professionals, and patients. In order to obtain a complete overview on utilization, associated health outcomes and costs of these drugs, it seems necessary to better interlink available databases.

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“…Most of patients treated with ICIs present with a variety of immune-related adverse events (IRAEs), including hepatitis, colitis, pneumonitis, thyroiditis, and so on. In addition, the severe adverse events can also have fatal consequences (Michot et al, 2016;Spain et al, 2016;Ali and Watson, 2017;Wang et al, 2017). Therefore, it is imperative to identify and analyses the NSCLC patients who can benefit from the treatment using ICIs.…”

Section: Introductionmentioning

confidence: 99%

First-Line Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Landscape and Future Progress

Huang

Lü

et al. 2020

Front. Pharmacol.

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Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhibitors (ICIs) can act on the inhibitory pathway of cancer immune response, thereby restoring and maintaining anti-tumor immunity. There are already ICIs targeting different pathways, including the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathway. Since March 2015, the US Food and Drug Administration (FDA) approved nivolumab (anti-PD-1 antibody) as the second-line option for treatment of patients with advanced squamous NSCLC. Additionally, a series of inhibitors related to PD-1/PD-L1 immune-checkpoints have helped in the immunotherapy of NSCLC patients, and modified the original treatment model. However, controversies remain regarding the use of ICIs in a subgroup with targeted oncogene mutations is a problem that we need to solve. On the other hand, there are continuous efforts to find biomarkers that effectively predict the response of ICIs to screen suitable populations. In this review, we have reviewed the history of the continuous developments in cancer immunotherapy, summarized the mechanism of action of the immune-checkpoint pathways. Finally, based on the results of the first-line recent trials, we propose a potential first-line immunotherapeutic strategy for the treatment of the patients with NSCLC.

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Pharmacovigilance Assessment of Immune‐Mediated Reactions Reported for Checkpoint Inhibitor Cancer Immunotherapies

Abstract: Cancer immunotherapy with CPIs is associated with a multitude of IMRs, especially colitis and pneumonitis. Individual CPIs had variable IMR signals, and pharmacoepidemiologic studies are required to evaluate the identified signals.

Cited by 33 publications

References 24 publications

Renal adverse effects following the use of different immune checkpoint inhibitor regimens: A real‐world pharmacoepidemiology study of post‐marketing surveillance data

Renal adverse effects following the use of different immune checkpoint inhibitor regimens: A real‐world pharmacoepidemiology study of post‐marketing surveillance data

Overview of French databases available for studying anticancer drugs in real‐life setting

First-Line Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Landscape and Future Progress

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