Disproportionality analysis in VigiBase as a drug repositioning method for the discovery of potentially useful drugs in Alzheimer's disease

Chrétien, Basile; Jourdan, Jean‐Pierre; Davis, Audrey; Fédrizzi, Sophie; Bureau, Ronan; Sassier, Marion; Rochais, Christophe; Alexandre, Jonas; Lelong‐Boulouard, Véronique; Dolladille, Charles; Dallemagne, Patrick

doi:10.1111/bcp.14690

Cited by 16 publications

(11 citation statements)

References 53 publications

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“…Though pharmacovigilance is traditionally used to detect signals of potential harm, more recently, spontaneous reporting systems have been exploited to uncover patterns indicative of reduced reporting (positive effects), e.g. for drug repurposing [15,16]. Furthermore, the consistency between trial results and pharmacovigilance analyses has been recently confirmed, thus raising the debate on the role of spontaneous reports as potential source of risk estimates under certain circumstances [17].…”

Section: Introductionmentioning

confidence: 99%

SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system

Bonora

Raschi

Avogaro

et al. 2021

Cardiovasc Diabetol

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Background Sodium glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of heart failure and new data show they can prevent atrial fibrillation (AF). We examined the association between SGLT2i and AF in the Food and Drug Administration adverse event reporting system (FAERS). Methods We mined the FAERS from 2014q1 to 2019q4 to compare AF reporting for SGLT-2 i versus reports for other glucose lowering medications (ATC10 class). Several exclusions were sequentially applied for: concomitant medications; diabetes, cardiovascular or renal disease indication; reports for competing adverse events (genitourinary tract infections, ketoacidosis, Fournier’s gangrene, amputation). We provide descriptive statistics and calculated proportional reporting ratios (PRR). Results There were 62,098 adverse event reports for SGLT2i and 642,031 reports for other ATC10 drugs. The reporting of AF was significantly lower with SGLT2i than with other ATC10 drugs (4.8 versus 8.7/1000; p < 0.001) with a PRR of 0.55 (0.49–0.62). Results did not change substantially after excluding reports listing insulin (PRR 0.49) or anti-arrhythmics (PRR 0.59) as suspect or concomitant drugs, excluding reports with indications for cardiovascular disease (PRR 0.49) or renal disease (PRR 0.55), and those filed for competing adverse events (PRR 0.63). Results were always statistically significant whether the diabetes indication was specified. Negative and positive controls confirmed internal validity of the database. Conclusions In a large pharmacovigilance database, AF was robustly and consistently reported more frequently for diabetes medications other than SGLT2i. This finding complements available evidence from trials supporting a protective role of SGLT2i against the occurrence of AF.

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Section: Introductionmentioning

confidence: 99%

SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system

Bonora

Raschi

Avogaro

et al. 2021

Cardiovasc Diabetol

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“…However, more recently, many Authors applied this approach to the FAERS and VigiBase to identify candidates for drug repositioning in a variety of clinical research areas (e.g., psychiatry, neurology, cardiology), by searching for an inverse signal, postulating that drugs that demonstrated an under-reporting of AEs of interest could be protective against these AEs (Wang et al, 2016;Horinouchi et al, 2018;Hosomi et al, 2018;Chrétien et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Growing number of evidence supports this innovative approach based on the use of pharmacovigilance databases, especially FAERS and VigiBase, to investigate promising new beneficial effects of drugs in real-world clinical practice, in a variety of clinical settings (e.g., psychiatry, neurology, cardiology) (Wang et al, 2016;Cohen et al, 2017;Carnovale et al, 2018;2019b;2019a;Horinouchi et al, 2018;Hosomi et al, 2018;Mazhar et al, 2019;Chrétien et al, 2021).…”

Section: Strengths and Limitationsmentioning

confidence: 99%

The potential antidepressant effect of antidiabetic agents: New insights from a pharmacovigilance study based on data from the reporting system databases FAERS and VigiBase

Battini

Manen²,

Gringeri

et al. 2023

Front. Pharmacol.

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Background: Growing evidence supports a bidirectional association between diabetes and depression; promising but limited and conflicting data from human studies support the intriguing possibility that antidiabetic agents may be used to relieve effectively depressive symptoms in diabetic patients. We investigated the potential antidepressant effects of antidiabetic drugs in a high-scale population data from the two most important pharmacovigilance databases, i.e., the FDA Adverse Event Reporting System (FAERS) and the VigiBase.Material and methods: From the two primary cohorts of patients treated with antidepressants retrieved from FDA Adverse Event Reporting System and VigiBase we identified cases (depressed patients experiencing therapy failure) and non-cases (depressed patients experiencing any other adverse event). We then calculated the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Empirical Bayes Regression-Adjusted Mean (ERAM) for cases versus non-cases in relation with the concurrent exposure to at least one of the following antidiabetic agent: A10BA Biguanides; A10BB Sulfonylureas; A10BG Thiazolidinediones; A10BH DPP4-inhibitors; A10BJ GLP-1 analogues; A10BK SGLT2 inhibitors (i.e., those agents for which preliminary evidence from literature supports our pharmacological hypothesis).Results: For GLP-1 analogues, all the disproportionality scores showed values <1, i.e., statistically significant, in both analyses [from the FAERS: ROR confidence interval of 0.546 (0.450–0.662); PRR (p-value) of 0.596 (0.000); EBGM (CI) of 0.488 (0.407–0.582); ERAM (CI) of 0.480 (0.398–0.569) and VigiBase: ROR (CI) of 0.717 (0.559–0.921); PRR (p-value) of 0.745 (0.033); EBGM (CI) of 0.586 (0.464–0.733); ERAM of (CI): 0.515 (0.403–0.639)]. Alongside GLP-1 analogues, DPP-4 Inhibitors and Sulfonylureas showed the greatest potential protective effect. With regard to specific antidiabetic agents, liraglutide and gliclazide were associated with a statistically significant decrease in all disproportionality scores, in both analyses.Conclusion: The findings of this study provide encouraging results, albeit preliminary, supporting the need for further clinical research for investigating repurposing of antidiabetic drugs for neuropsychiatric disorders.

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“…Among the potential benefits of clozapine is the low incidence of neurological side effects, even with long‐term use; potential disadvantages include important side effects such as sedation and agranulocytosis 13 . In the treatment of dementia, its anticholinergic effects are feared with the risk of inducing delirium, 14 although a potential inhibition of acetylcholinesterase and butyrylcholinesterase may counteract this 15 . Due to its specific pharmacological properties, clozapine could also play a special role in the treatment of old adults with dementia, as it may be effective in controlling severe behavioural symptoms.…”

Section: Introductionmentioning

confidence: 99%

Clozapine for the treatment of aggressiveness and agitation in advanced dementia

Michael,

Erfurth

et al. 2023

Psychogeriatrics

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BackgroundDistressing behavioural symptoms, particularly agitation and aggressiveness, remain a difficult problem in everyday clinical practice in the treatment of multimorbid patients with dementia. Clozapine may be an effective therapeutic alternative in this context.MethodsIn a retrospective study, patients who had a diagnosis of dementia and had been treated in a specialized geriatric psychiatry unit with clozapine between August 2018 and February 2022 were included, and medical records were systematically reviewed. The Clinical Global Impressions Scale was used to assess improvement, and the Pittsburgh Agitation Scale for symptom reduction. In addition, side effects and clinical features were documented in detail.ResultsA total of 31 patients (median age 82 years) were identified with a mean clozapine dose of 47.2 (SD 35.6) mg. A total of 13 patients tolerated clozapine very well, 10 showed tolerable side effects, and in 10 patients side effects were the reason for stopping clozapine. Behavioural symptoms improved significantly, as indicated by the assessment scores.ConclusionsIn summary, clozapine was effective and well tolerated in 23 patients, suggesting that low‐dose clozapine may help to alleviate the suffering of difficult‐to‐treat multimorbid patients with advanced dementia and their caregivers. However, particular attention should be paid to adverse drug reactions, especially in patients with cardiovascular and pulmonary impairment.

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Disproportionality analysis in VigiBase as a drug repositioning method for the discovery of potentially useful drugs in Alzheimer's disease

Cited by 16 publications

References 53 publications

SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system

SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system

The potential antidepressant effect of antidiabetic agents: New insights from a pharmacovigilance study based on data from the reporting system databases FAERS and VigiBase

Clozapine for the treatment of aggressiveness and agitation in advanced dementia

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