Acute kidney injury following the use of different proton pump inhibitor regimens: A real-world analysis of post-marketing surveillance data.

Recent evidence has concerned acute kidney injury (AKI) after the proton pump inhibitor (PPI) application. There are few real-world studies to compare the occurrences, clinical features, and prognosis of AKI related to various PPI regimens. We aimed to evaluate and compare the links between different PPIs and AKI in a large population by investigating the Food and Drug Administration Adverse Event Reporting System (FAERS) until recently. Disproportionality analysis and Bayesian analysis were used in data mining to screen the suspected AKI after different PPIs based on the FAERS from January 2004 to December 2019. The times to onset, fatality, and hospitalization rates of PPI-associated AKI were also investigated. We identified 19 522 PPI-associated AKIs, which appeared to influence more middle-aged patients than elderly ones (53.04% vs 33.94%). Women were more affected than men (55.42% vs 44.58%). Lansoprazole appeared a stronger AKI association than other PPIs, based on the highest reporting odds ratio (reporting odds ratio = 20.8, 95% confidence interval = 20.16, 21.46), proportional reporting ratio (proportional reporting ratio = 15.55, χ2  = 73 899.68), and empirical Bayes geometric mean (empirical Bayes geometric mean = 15.15, 95% confidence interval = 14.76). The median time to AKI onset was 446 (interquartile range [IQR] 16-2176) days after PPI administration. PPIs showed a significant difference in average time to AKI onset (P < 0.001), with the shortest of 9 (IQR 3-25) days for rabeprazole and the longest of 1221 (IQR 96.5-2620) days for esomeprazole. PPI-associated AKI generally led to a 5.69% fatality rate and an 8.94% hospitalization rate. The highest death rate occurred in rabeprazole (15.35%). Based on the FAERS database, we profiled AKI related to various PPIs with more details in occurrences, clinical characteristics, and prognosis. Concern should be paid for PPIs when applied to patients with a tendency for AKI.

Chen G ，Ning LJ ，Qin Y ，Zhao B ，Mei D ，Li XM ... -  《-》

Syndrome of inappropriate antidiuretic hormone secretion is associated with different proton pump inhibitor use: a pharmacovigilance study.

The objective of this study was to evaluate the reported associations between the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and a variety of proton pump inhibitors (PPI) through analysis of the reports extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). FAERS reports from January 2004 to March 2020 were used to conduct disproportionality and Bayesian analyses. The definition of SIADH relied on the preferred terms provided by the Medical Dictionary for Regulatory Activities. The time to onset, mortality, and hospitalization rates of PPI-related SIADH were also investigated. The study identified a total of 273 reports of PPI-associated SIADH, which appeared to influence more elderly than middle-aged patients (71.1% vs. 12.5%). Women were more affected than men (48.7% vs. 41.8%). Rabeprazole had a stronger SIADH association than other PPIs based on the highest reporting odds ratio (reporting odds ratio = 13.3, 95% confidence interval (CI) = 7.2, 24.9), proportional reporting ratio (proportional reporting ratio = 13.3, χ2 = 113.7), and empirical Bayes geometric mean (empirical Bayes geometric mean = 13.3, 95% CI = 7.9). The median time to SIADH onset was 22 (interquartile range 6-692) days after PPI administration. PPI-associated SIADH generally led to a 2.95% fatality rate and a 79.7% hospitalization rate. The highest hospitalization death rate occurred in esomeprazole (91.2%). According to our findings, more attention should be paid to SIADH within the first several months after the administration of PPIs. For women older than 65 years, dexlansoprazole may reduce the incidence of PPI-associated SIADH. Nonetheless, larger epidemiological studies are suggested to verify this conclusion.

Wang M ，Zhang L ，Jia M ，Wang J ，Shen Z ，Wang S ，Zhang X ，Xu J ，Zheng Z ，Lv X ，Zong X ，Li H ，Zhou J ，Meng T ，Chen M ，Zhao B ，Gong J ... -  《BMC Nephrology》

Proton pump inhibitors associated acute kidney injury and chronic kidney disease: data mining of US FDA adverse event reporting system.

Wu B ，Li D ，Xu T ，Luo M ，He Z ，Li Y ... -  《Scientific Reports》

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

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. 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. 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. 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.

Chen G ，Qin Y ，Fan QQ ，Zhao B ，Mei D ，Li XM ... -  《Cancer Medicine》

A pharmacovigilance study of association between proton-pump inhibitors and rhabdomyolysis event based on FAERS database.

The association between proton-pump inhibitors (PPIs) and rhabdomyolysis were unclear. The aim of this study was to explore and systematically analyze the potential link between five PPIs and the rhabdomyolysis events using the FDA Adverse Event Reporting System (FAERS) database. Suspected rhabdomyolysis events associated with PPIs were identified by data mining with the reporting odds ratio (ROR), proportional reporting ratio (PRR), the information component (IC), and Empirical Bayes Geometric Mean (EBGM). Demographic information, drug administration, and outcomes of PPI-induced rhabdomyolysis events were also analyzed. There were 3311 reports associated with PPI-induced rhabdomyolysis that were identified. After removing duplicates, 1899 cases were determined to contain complete patient demographic data. The average age was 65 ± 18 year and 57% were male. Omeprazole and pantoprazole had the same largest percentage of reports. Lansoprazole had the highest ROR index of 12.67, followed by esomeprazole (11.18), omeprazole (10.27), rabeprazole (10.06), and pantoprazole (9.24). PRR, IC, and EBGM showed similar patterns. This suggested that lansoprazole exhibited the strongest correlation with rhabdomyolysis. In rhabdomyolysis events, PPIs were mainly "concomitant" (>60%), and only a few cases were "primary suspects" (<15%). Rabeprazole showed the lowest death rate while lansoprazole showed the highest. The study suggested that significant rhabdomyolysis signals were associated with PPIs. Further research should be performed in drug safety evaluation for a more comprehensive association.

Sun Y ，Zhang A ，Zuo M ，Chen J ，Zhu L ... -  《-》