Search

Vaso-occlusive episodes (VOEs) are a major concern in patients with sickle cell disease (SCD). Exposure to systemic corticosteroids has been suspected to increase the occurrence of VOEs in case reports or series. No comparative study has been conducted to investigate this risk, which is still debated. Several clinical trials demonstrated the effectiveness of corticosteroids for the treatment of VOEs, but with increased rates of readmission. The aim of the study was to assess the risk of hospitalization for VOE associated with exposure to systemic corticosteroids in patients with SCD. We used a case-case-time-control design in a nationwide population-based cohort built in the French national health insurance database between 2010 and 2018. The population included all patients with SCD with at least 1 hospitalization for VOE. Corticosteroids were identified using out-of-hospital dispensing data. The outcome was the first hospitalization for VOE. The case-case-time-control design induces self-adjustment for time-invariant confounders, including genotype. Analyses were adjusted for time-dependent confounders (infections, red blood transfusions) and stratified by exposure to hydroxyurea. Overall, 5151 patients were included in the main analysis. Corticosteroid exposure was significantly associated with the occurrence of hospitalizations for VOEs: adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.4-5.6). In patients exposed to hydroxyurea, the adjusted odds ratio was 2.6 (95% CI, 1.1-6.4); it was 4.0 (95% CI, 2.5-6.3) in unexposed patients. These results were consistent in children and adults. In conclusion, systemic corticosteroids were associated to an increased risk of hospitalization for VOEs and should be limited in patients with SCD.

Vaso-occlusive episodes (VOEs) are a major concern in patients with sickle cell disease (SCD). Exposure to systemic corticosteroids has been suspected to increase the occurrence of VOEs in case reports or series. No comparative study has been conducted to investigate this risk, which is still debated. Several clinical trials demonstrated the effectiveness of corticosteroids for the treatment of VOEs, but with increased rates of readmission. The aim of the study was to assess the risk of hospitalization for VOE associated with exposure to systemic corticosteroids in patients with SCD. We used a case-case-time control design in a nationwide population-based cohort built in the French national health insurance database between 2010 and 2018. The population included all patients with SCD with at least one hospitalization for VOE. Corticosteroids were identified using out-of-hospital dispensing data. The outcome was the first hospitalization for VOE. The case-case-time-control design induces self-adjustment for time-invariant confounders, including genotype. Analyses were adjusted for time-dependent confounders (infections, red blood transfusions) and stratified by exposure to hydroxyurea. Overall, 5,151 patients were included in the main analysis. Corticosteroid exposure was significantly associated with the occurrence of hospitalizations for VOEs: adjusted Odds Ratio (aOR): 3.8 (95% Confidence Interval - CI: 2.4-5.6). In patients exposed to hydroxyurea, the aOR was 2.6 (95% CI: 1.1-6.4); it was 4.0 (95% CI: 2.5-6.3) in unexposed patients. These results were consistent in children and adults. In conclusion, systemic corticosteroids were associated to an increased risk of hospitalization for VOE and should be limited in patients with SCD.

•This study identified 59 new signals of drug-induced immune hemolytic anemia in Vigibase®.•An association was found for some antibiotics, antifungal drugs, ibuprofen, acetaminophen, furosemide, azathioprine and iomeprol.

Bartolucci: GBT: Consultancy; Emmaus: Consultancy; Fabre Foundation: Research Funding; AGIOS: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Jazz Pharma: Other: Lecture fees; INNOVHEM: Other: Co-founder; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; Hemanext: Consultancy; Addmedica: Consultancy, Other: Lecture fees, Research Funding. Moulis: Argenx: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Hansen: Novartis: Research Funding; Alexion: Research Funding. Berentsen: True North Therapeutics: Consultancy; Sanofi: Consultancy, Honoraria; Janssen-Cilag: Honoraria; Bioverativ: Consultancy, Honoraria; Mundipharma: Research Funding; Apellis Pharmaceuticals: Consultancy, Honoraria; Alexion Pharmaceuticals, Inc: Honoraria. Frederiksen: Novartis: Research Funding; Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding. Moulis: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenix: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees.

Introduction

Moulis: Grifols: Research Funding; Amgen: Other: meeting attendance grant; Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding.

Moulis: CSL Behring: Research Funding; Amgen pharma: Research Funding, Speakers Bureau; Novartis pharma: Research Funding, Speakers Bureau.

Introduction:Hemolytic anemia is a group of rare diseases. National databases are useful data sources to assess the epidemiology and the management of such diseases. The French national health database covers the entire French population (66 million inhabitants). It links sociodemographic data, out-hospital data including dispensing data and hospital data. As a consequence, this database is very useful for population-based studies on rare diseases. For instance, it has been used for epidemiological and pharmacoepidemiological studies on immune thrombocytopenia. Diseases are identified using the national hospital database (named PMSI) that contains discharge diagnoses for all hospital stays in all private and public hospitals in France. This study was aimed at assessing the positive predictive value (PPV) of hemolytic anemia diagnoses in the French hospital database.