Search

Your search keyword '"Dolladille, Charles"' showing total 265 results
Start Over Author "Dolladille, Charles"
265 results on '"Dolladille, Charles"'

5. The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration

Author

Fusaroli, Michele, Salvo, Francesco, Begaud, Bernard, AlShammari, Thamir M., Bate, Andrew, Battini, Vera, Brueckner, Andreas, Candore, Gianmario, Carnovale, Carla, Crisafulli, Salvatore, Cutroneo, Paola Maria, Dolladille, Charles, Drici, Milou-Daniel, Faillie, Jean-Luc, Goldman, Adam, Hauben, Manfred, Herdeiro, Maria Teresa, Mahaux, Olivia, Manlik, Katrin, Montastruc, François, Noguchi, Yoshihiro, Norén, G. Niklas, Noseda, Roberta, Onakpoya, Igho J., Pariente, Antoine, Poluzzi, Elisabetta, Salem, Myriam, Sartori, Daniele, Trinh, Nhung T. H., Tuccori, Marco, van Hunsel, Florence, van Puijenbroek, Eugène, Raschi, Emanuel, and Khouri, Charles

Published
2024
Full Text
View/download PDF

6. The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Development and Statement

Author

Fusaroli, Michele, Salvo, Francesco, Begaud, Bernard, AlShammari, Thamir M., Bate, Andrew, Battini, Vera, Brueckner, Andreas, Candore, Gianmario, Carnovale, Carla, Crisafulli, Salvatore, Cutroneo, Paola Maria, Dolladille, Charles, Drici, Milou-Daniel, Faillie, Jean-Luc, Goldman, Adam, Hauben, Manfred, Herdeiro, Maria Teresa, Mahaux, Olivia, Manlik, Katrin, Montastruc, François, Noguchi, Yoshihiro, Norén, G. Niklas, Noseda, Roberta, Onakpoya, Igho J., Pariente, Antoine, Poluzzi, Elisabetta, Salem, Myriam, Sartori, Daniele, Trinh, Nhung T. H., Tuccori, Marco, van Hunsel, Florence, van Puijenbroek, Eugène, Raschi, Emanuel, and Khouri, Charles

Published
2024
Full Text
View/download PDF

10. Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis

Author

Fenioux, Charlotte, Abbar, Baptiste, Boussouar, Samia, Bretagne, Marie, Power, John R., Moslehi, Javid J., Gougis, Paul, Amelin, Damien, Dechartres, Agnès, Lehmann, Lorenz H., Courand, Pierre-Yves, Cautela, Jennifer, Alexandre, Joachim, Procureur, Adrien, Rozes, Antoine, Leonard-Louis, Sarah, Qin, Juan, Cheynier, Rémi, Charmeteau-De Muylder, Benedicte, Redheuil, Alban, Tubach, Florence, Cadranel, Jacques, Milon, Audrey, Ederhy, Stéphane, Similowski, Thomas, Johnson, Douglas B., Pizzo, Ian, Catalan, Toniemarie, Benveniste, Olivier, Hayek, Salim S., Allenbach, Yves, Rosenzwajg, Michelle, Dolladille, Charles, and Salem, Joe-Elie

Published
2023
Full Text
View/download PDF

11. Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database.

Author

Nguyen, Lee, Cooper, Leslie, Kerneis, Mathieu, Funck-Brentano, Christian, Silvain, Johanne, Brechot, Nicolas, Hekimian, Guillaume, Ammirati, Enrico, Ben MBarek, Badr, Redheuil, Alban, Gandjbakhch, Estelle, Bihan, Kevin, Lebrun-Vignes, Bénédicte, Ederhy, Stephane, Dolladille, Charles, Moslehi, Javid, and Salem, Joe-Elie

Subjects
Adverse Drug Reaction Reporting Systems, Antineoplastic Agents, Antipsychotic Agents, Bayes Theorem, Cross-Sectional Studies, Data Management, Databases, Factual, Humans, Immunotherapy, Myocarditis, Pharmaceutical Preparations, Pharmacovigilance, Systems Analysis, World Health Organization
Abstract

While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n = 3108 reports), salicylates (n = 340), antineoplastic-cytotoxics (n = 190), antineoplastic-immunotherapies (n = 538), and vaccines (n = 790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n = 3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 [interquartile range: 10; 23] days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis.

Published
2022

14. Publisher Correction: Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis

Author

Fenioux, Charlotte, Abbar, Baptiste, Boussouar, Samia, Bretagne, Marie, Power, John R., Moslehi, Javid J., Gougis, Paul, Amelin, Damien, Dechartres, Agnès, Lehmann, Lorenz H., Courand, Pierre-Yves, Cautela, Jennifer, Alexandre, Joachim, Procureur, Adrien, Rozes, Antoine, Leonard-Louis, Sarah, Qin, Juan, Cheynier, Rémi, Charmeteau-De Muylder, Benedicte, Redheuil, Alban, Tubach, Florence, Cadranel, Jacques, Milon, Audrey, Ederhy, Stéphane, Similowski, Thomas, Johnson, Douglas B., Pizzo, Ian, Catalan, Toniemarie, Benveniste, Olivier, Hayek, Salim S., Allenbach, Yves, Rosenzwajg, Michelle, Dolladille, Charles, and Salem, Joe-Elie

Published
2024
Full Text
View/download PDF

16. Author Correction: Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis

Author

Fenioux, Charlotte, Abbar, Baptiste, Boussouar, Samia, Bretagne, Marie, Power, John R., Moslehi, Javid J., Gougis, Paul, Amelin, Damien, Dechartres, Agnès, Lehmann, Lorenz H., Courand, Pierre-Yves, Cautela, Jennifer, Alexandre, Joachim, Procureur, Adrien, Rozes, Antoine, Leonard-Louis, Sarah, Qin, Juan, Cheynier, Rémi, Charmeteau-De Muylder, Benedicte, Redheuil, Alban, Tubach, Florence, Cadranel, Jacques, Milon, Audrey, Ederhy, Stéphane, Similowski, Thomas, Johnson, Douglas B., Pizzo, Ian, Catalan, Toniemarie, Benveniste, Olivier, Hayek, Salim S., Allenbach, Yves, Rosenzwajg, Michelle, Dolladille, Charles, and Salem, Joe-Elie

Published
2023
Full Text
View/download PDF

20. Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis

Author

Dolladille, Charles, Font, Jonaz, Bejan-Angoulvant, Theodora, Zaman, Khalil, Sassier, Marion, Ezine, Emilien, Stefan, Andreea, Plane, Anne-Flore, Legallois, Damien, Milliez, Paul, Parienti, Jean-Jacques, and Alexandre, Joachim

Published
2020
Full Text
View/download PDF

24. Association between antidepressant use and delirium in older adults: an analysis of the World Health Organization’s global pharmacovigilance database

Author

Minoc, Elise-Marie, primary, Villain, Cédric, additional, Benbrika, Soumia, additional, Chrétien, Basile, additional, Descatoire, Pablo, additional, Heraudeau, Marie, additional, Sassier, Marion, additional, Pierre, Mélissa, additional, Martinaud, Olivier, additional, Dolladille, Charles, additional, and Lelong-Boulouard, Véronique, additional

Published
2024
Full Text
View/download PDF

25. Arterial hypertension associated with PARPi: A meta‐analysis of 41 placebo randomized controlled trials combined with a World Health Organization's pharmacovigilance study.

Author

Blaize, Clémence, Surtouque, Ellina, Font, Jonaz, Dolladille, Charles, Postel‐Vinay, Sophie, Da Silva, Angélique, Alexandre, Joachim, and Morice, Pierre‐Marie

Subjects
POLY ADP ribose, UBIQUINONES, HYPERTENSION, WORLD health, SURVIVAL analysis (Biometry), RANDOMIZED controlled trials, PLACEBOS
Abstract

Background: Arterial hypertension has been recently reported from randomized controlled trials (RCTs) assessing poly (ADP‐ribose) polymerase inhibitor (PARPi). Objective: In a context of increasing use of PARPi, it is crucial to properly assess risk and incidence of this adverse event for clinical practice. Methods: We performed a systematic review and meta‐analysis in MEDLINE, Cochrane CENTRAL and ClinicalTrials.gov up to January 4, 2023 with an ongoing surveillance up to June 7, 2023. RCTs comparing PARPi to placebo in adult patients with solid tumors were included if hypertension was reported. The primary outcome was the summary risk ratio (RR, with 95% CIs) of any hypertension of PARPi class in placebo RCTs. Secondary outcomes were the summary risk and incidence of hypertension of each individual PARPi. To provide clinical features of PARPi‐associated hypertension, we independently queried the WHO's pharmacovigilance database, up to September 1, 2022. Results: In total, 41 placebo RCTs (n = 15 264 adult patients) were included. PARPi class was not associated with an increased risk of hypertension compared with placebo. In individual analyses, the risk of hypertension was lower with olaparib than placebo (RR 0.77 [95% CI: 0.68–0.86], P < 0.01; I2 = 19%, χ2P = 0.26). Niraparib monotherapy increased the risk of any (RR 2.84 [95% CI: 1.76–4.57], P < 0.01; I2 = 66%, χ2P = 0.01) hypertension with a summary incidence of 19.87% (95% CI: 15.23–25.50). In real‐life setting, niraparib‐associated hypertension occurs within 20 days and was serious in 66%. Co‐prescription of at least one antihypertensive or therapy‐induced hypertension was reported in 20.5% or 14.4% of cases, respectively. Conclusions: In a context of extensive assessment of niraparib in combination, these data reinforce the need of a close monitoring of this adverse event to preserve its clinical benefit on patients' survival. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

28. Neurocognitive impairment in females with breast cancer treated with endocrine therapy and CDK4/6 inhibitors: a pharmacovigilance study using the World Health Organization’s database

Author

Prevost, Rachel, primary, Chretien, Basile, additional, Minoc, Elise-Marie, additional, Dolladille, Charles, additional, Da-Silva, Angélique, additional, Nehme, Ahmad, additional, Joly, Florence, additional, Lelong-Boulouard, Véronique, additional, and Bastien, Etienne, additional

Published
2023
Full Text
View/download PDF

34. CTLA-4 Pathway Is Instrumental in Giant Cell Arteritis

Author

Régnier, Paul, primary, Le Joncour, Alexandre, additional, Maciejewski-Duval, Anna, additional, Darrasse-Jèze, Guillaume, additional, Dolladille, Charles, additional, Meijers, Wouter C., additional, Bastarache, Lisa, additional, Fouret, Pierre, additional, Bruneval, Patrick, additional, Arbaretaz, Floriane, additional, Sayetta, Célia, additional, Márquez, Ana, additional, Rosenzwajg, Michelle, additional, Klatzmann, David, additional, Cacoub, Patrice, additional, Moslehi, Javid J., additional, Salem, Joe-Elie, additional, and Saadoun, David, additional

Published
2023
Full Text
View/download PDF

37. CTLA-4 Pathway Is Instrumental in Giant Cell Arteritis

Author

European Commission, Régnier, Paul, Le Joncour, Alexandre, Maciejewski-Duval, Anna, Darrasse-Jèze, Guillaume, Dolladille, Charles, Meijers, Wouter C., Bastarache, Lisa, Fouret, Pierre, Bruneval, Patrick, Arbaretaz, Florianne, Sayetta, Célia, Márquez, Ana, Rosenzwajg, Michelle, Klatzmann, David, Cacoub, Patrice, Moslehi, Javid J., Salem, Joe-Elle, Saadoun, David, European Commission, Régnier, Paul, Le Joncour, Alexandre, Maciejewski-Duval, Anna, Darrasse-Jèze, Guillaume, Dolladille, Charles, Meijers, Wouter C., Bastarache, Lisa, Fouret, Pierre, Bruneval, Patrick, Arbaretaz, Florianne, Sayetta, Célia, Márquez, Ana, Rosenzwajg, Michelle, Klatzmann, David, Cacoub, Patrice, Moslehi, Javid J., Salem, Joe-Elle, and Saadoun, David

Abstract

BACKGROUND: Giant cell arteritis (GCA) causes severe inflammation of the aorta and its branches and is characterized by intense effector T-cell infiltration. The roles that immune checkpoints play in the pathogenesis of GCA are still unclear. Our aim was to study the immune checkpoint interplay in GCA. METHODS: First, we used VigiBase, the World Health Organization international pharmacovigilance database, to evaluate the relationship between GCA occurrence and immune checkpoint inhibitors treatments. We then further dissected the role of immune checkpoint inhibitors in the pathogenesis of GCA, using immunohistochemistry, immunofluorescence, transcriptomics, and flow cytometry on peripheral blood mononuclear cells and aortic tissues of GCA patients and appropriated controls. RESULTS: Using VigiBase, we identified GCA as a significant immune-related adverse event associated with anti-CTLA-4 (cytotoxic T-lymphocyte¿associated protein-4) but not anti-PD-1 (anti-programmed death-1) nor anti-PD-L1 (anti-programmed death-ligand 1) treatment. We further dissected a critical role for the CTLA-4 pathway in GCA by identification of the dysregulation of CTLA-4¿derived gene pathways and proteins in CD4+ (cluster of differentiation 4) T cells (and specifically regulatory T cells) present in blood and aorta of GCA patients versus controls. While regulatory T cells were less abundant and activated/suppressive in blood and aorta of GCA versus controls, they still specifically upregulated CTLA-4. Activated and proliferating CTLA-4+ Ki-67+ regulatory T cells from GCA were more sensitive to anti-CTLA-4 (ipilimumab)¿mediated in vitro depletion versus controls. CONCLUSIONS: We highlighted the instrumental role of CTLA-4 immune checkpoint in GCA, which provides a strong rationale for targeting this pathway.

Published
2023

39. Diagnostic Value of the International Society of Cardio‐Oncology Definition for Suspected Immune Checkpoint Inhibitor–Associated Myocarditis

Author

Deharo, Francois, primary, Thuny, Franck, additional, Cadour, Farah, additional, Resseguier, Noemie, additional, Meilhac, Alexandra, additional, Gaubert, Melanie, additional, Dolladille, Charles, additional, Paganelli, Franck, additional, Alexandre, Joachim, additional, and Cautela, Jennifer, additional

Published
2023
Full Text
View/download PDF

41. Infections associated with clozapine: a pharmacovigilance study using VigiBase®.

Author

Chrétien, Basile, Brazo, Perrine, Da Silva, Angélique, Sassier, Marion, Dolladille, Charles, Lelong-Boulouard, Véronique, Alexandre, Joachim, and Fedrizzi, Sophie

Subjects
CLOZAPINE, DRUG monitoring, OLANZAPINE, CONCOMITANT drugs, VALPROIC acid, PROTON pump inhibitors, CLARITHROMYCIN, ARIPIPRAZOLE
Abstract

Introduction: Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine, which may lead to elevated serum levels of the drug. However, the existing literature on this topic is limited. Therefore, we conducted a study using VigiBase® to investigate the potential over-reporting of infections associated with clozapine, to explore the presence of dosedependency, and to investigate the underlying mechanism. Methods: Disproportionality analyses were performed using VigiBase to assess the association between clozapine and all types of infections, the association between clozapine-associated infections and neutropenia, the association between clozapine-associated infections and agranulocytosis, the dose–effect relationship between clozapine and infections, and the interaction between clozapine and the main strong CYP450 inhibitors using reports carried out until 11 April 2023. Results: A statistically significant signal of infections was observed with clozapine, as indicated by an information component of 0.43 [95% CI: (0.41–0.45)]. The most commonly reported infections were respiratory and gastrointestinal in nature. Neutropenia showed weaker association with clozapine-associated reports of infections compared to other clozapine-associated reports [X2 (1, N = 204,073) = 454; p < 0.005], while agranulocytosis demonstrated a stronger association with clozapine-associated reports of infections [X2 (1, N = 204,073) = 56; p < 0.005]. No evidence of dose-dependency was observed. Among the 17 tested CYP inhibitors, significant drug–drug interactions were found with clarithromycin, metronidazole, valproic acid, lansoprazole, omeprazole, amiodarone, and esomeprazole. Discussion: Our study revealed a significant safety signal between clozapine use and infections, predominantly respiratory and gastrointestinal infections. The coadministration of clozapine with valproic acid or proton pump inhibitors may potentially contribute to an increased risk of infection. Further vigilance is warranted in clinical practice, and consideration of therapeutic drug monitoring of clozapine in cases involving concomitant use of these drugs or in the presence of infections may be beneficial. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

44. COVID-19 vaccines associated with vasovagal malaise: A retrospective study in two mass vaccination centers and analysis of the WHO pharmacovigilance database

Author

Chrétien, Basile, primary, Stroiazzo, Rhéda, additional, Troussier, Leila, additional, Le Houssel, Pierre-Yves, additional, Jacquet, Magali, additional, Lheureux, Cécile, additional, Voyen, Sandy, additional, Court, Philippe, additional, Dolladille, Charles, additional, Alexandre, Joachim, additional, Fedrizzi, Sophie, additional, and Humbert, Xavier, additional

Published
2022
Full Text
View/download PDF

45. Hypoxia Associated With Dihydropyridine Calcium Channel Inhibitors: A Pharmacovigilance Study in VigiBase.

Author

Chrétien, Basile, Decros, Jean Baptiste, Suard, Florimond, Dolladille, Charles, Fischer, Marc‐Olivier, Alexandre, Joachim, and Descamps, Richard

Subjects
CALCIUM channels, DIHYDROPYRIDINE, HYPOXEMIA, DRUG side effects, ORAL drug administration, COBALT chloride, CALCIUM
Abstract

Due to their negative effects on hypoxic pulmonary vasoconstriction, dihydropyridine calcium channel inhibitors (DCCIs) can lead to hypoxia in patients with a pulmonary shunt. To date, only preclinical studies and case reports have focused on this potential adverse drug reaction. We aimed to assess the reporting association between DCCIs and hypoxia using the World Health Organization pharmacovigilance database (VigiBase). We performed a disproportionality analysis to evaluate the strength of the reporting association between i.v. clevidipine and nicardipine, thought to be a surrogate of patients in the intensive care unit, and hypoxia. The information component and the lower end of its 95% credibility interval were used to evaluate disproportionality. A description of the cases was made. Secondary outcomes included the association between all DCCIs and hypoxia compared with other treatments with similar indications, urapidil and labetalol, regardless of the route of administration. Association between oral nicardipine and hypoxia was also searched. A statistically significant signal of hypoxia was found for intravenous clevidipine and nicardipine. The time to onset was reported with a median of 2 days (interquartile range 1.5–4.5). Four dechallenges were performed with intravenous nicardipine, leading to the resolution of the symptoms. Regardless of the route of administration, a signal of hypoxia was also found for nimodipine but not for other drugs, including comparators. For nicardipine no signal of hypoxia was found with the oral route of administration. Our pharmacovigilance database analysis showed a significant association between the use of intravenous DCCIs and hypoxia. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

47. Association between road traffic accidents and drugs belonging to the antiseizure medications class: A pharmacovigilance analysis in VigiBase

Author

Chrétien, Basile, primary, Nguyen, Sophie, additional, Dolladille, Charles, additional, Morice, Pierre‐Marie, additional, Heraudeau, Marie, additional, Loilier, Magalie, additional, Fedrizzi, Sophie, additional, Bourgine, Joanna, additional, Cesbron, Alexandre, additional, Alexandre, Joachim, additional, Bocca, Marie‐Laure, additional, Freret, Thomas, additional, and Lelong‐Boulouard, Véronique, additional

Published
2022
Full Text
View/download PDF

48. Pharmacological methodological approaches and input of pharmacovigilance databases on detecting and describing rare adverse effects : use in onco-pharmacology

Author

Dolladille, Charles, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université, Joachim Alexandre, and STAR, ABES

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Etiology, Onco-pharmacologie, Adverse effects, Pharmacoepidemiology, Neoplasms, Antineoplastic agents, Methods, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Context: Standard methods for the detection and quantification of safety signals may be inefficient in the field of onco-pharmacology, especially in rare settings. Materials and methods: We developed four new methods based on pharmacovigilance databases and safety meta-analysis. Results: In an adjusted disproportionality analysis following missing data imputation, we highlighted an association between some disease modifying therapies prescribed to persons with multiple sclerosis. The model added meaningful clinical readability, thanks to the adjustment. Added value of having missing data imputed was poor on both magnitude and precision of the estimates. The rechallenge was described following immune-related adverse effects of immune checkpoint inhibitors, in a large cohort (452 cases). We described use of rechallenge in multiple settings, including by type of adverse effect, and we computed a recurrence rate. Factors associated with over-reporting of recurrence and, in a separate work, of mortality, were performed among immunotherapy-related cases. We identified drug-, concurrent conditions-related and administrative factors associated with these outcomes. The prioritization of data sources in the safety meta-analysis allowed for an almost two-fold higher detection of cardiovascular adverse events, in immune checkpoint inhibitors randomized clinical trials, as compared with standard methods, although the research setting was very close (number of patients, number of studies, dates). Conclusions: Drug rechallenge, factors associated with over-reporting of outcomes, and the prioritization of data sources in the meta-analysis appear very meaningful methods. Dedicated evaluation of these methods is warranted to determine how and when to use them, as compared with the standard ones. Further development could look for more clinically explaining models, as with mediation analyses, or move to automatized meta-analysis processes for large scale quantification of drug efficacy and safety. Ultimately, developing these methods would improve detection and quantification of safety signals and lead to better use of drugs in onco-pharmacology., Contexte : Les méthodes classiques de détection et quantification des signaux de sécurité en onco-pharmacologie peuvent être prises en défaut, spécialement dans des situations cliniques rares. Matériel et méthodes : Dans ce travail, nous avons développé quatre nouveaux outils méthodologiques, à la fois dans le champ de l’analyse de disproportionalité en base de pharmacovigilance et dans le champ de la méta-analyse de sécurité. Résultats : Dans un modèle d’analyse ajusté après imputation des données manquantes, nous avons mis en évidence une association entre certains médicaments de la sclérose en plaques et notification de cancer. Ce modèle apportait une lisibilité clinique aux résultats grâce à l’analyse ajustée. L’apport de l’imputation des données manquantes sur l’estimation et sa précision était modeste. La description de la réintroduction des médicaments inhibiteurs de point de contrôle immunitaire après un effet indésirable immuno-médié portait sur la plus grande cohorte publiée à cette date (452 cas). Nous avons pu décrire l’utilisation de la réintroduction, notamment par type d’effet indésirable, et calculer un taux de récurrence. L’analyse des facteurs associés à la surnotification de récurrence puis, dans un second travail, celle des facteurs associés à la surnotification de mortalité portait sur des familles d’immunothérapie. Nous avons identifié des facteurs liés d’une part au médicament, d’autre part aux comorbidités des patients, et des éléments administratifs susceptibles d’expliquer la surnotification de ces évènements. En priorisant les sources de données de la méta-analyse de sécurité et en conduisant une analyse systématique de la base de données ClinicalTrials.gov, nous avons pu estimer le risque d’immunotoxicité cardiovasculaire des inhibiteurs de point de contrôle immunitaire, à partir des essais cliniques randomisés. La détection des évènements indésirables était nettement supérieure à celle des techniques usuelles : pour un nombre de patients et d’études similaires et sur une même période de temps, pratiquement deux fois plus d’évènements indésirables étaient recensés par cette méthode. Discussion et perspectives : La réintroduction des médicaments, les facteurs de surnotification d’évènement, et la méthode de méta-analyse sont particulièrement intéressants et nécessitent des études comparatives dédiées, pour déterminer leur place par rapport aux stratégies conventionnelles. Le développement futur de ces méthodes peut s’orienter vers davantage de signification clinique, par exemple à l’aide des analyses de médiation, ou encore l’automatisation des processus pour la mise à disposition à grande échelle de données quantifiées fiables d’efficacité et sécurité du médicament. Développer ces méthodes permettrait d’améliorer la détection et la quantification des signaux de sécurité, donc le bon usage du médicament en onco-pharmacologie.

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results