title: Off-label use of the expensive orphan drug eculizumab in France 2009-2013 and the impact of literature: focus on the transplantation field.
abstract: OBJECTIVE
  The orphan drug eculizumab (Soliris ®) is one of the most expensive in the world and based on expenditures is classed among the highest in France, a scenario suggestive of off-label use. Given its pharmacological properties, it is likely to be used in organ transplantation. Our purposes were to describe the consumption trends of eculizumab for off-label indications overall and in the organ transplantation field and to assess the impact of publications on the latter use.
  
  
  METHODS
  We carried out a temporal ecological study within the French national hospitalization database (PMSI). First, the trend of eculizumab consumption (2009-2013) was compared to our estimate of the maximum on-label consumption (overall and for transplantation). Second, we evaluated the impact of the publications supporting the effectiveness of eculizumab in the transplantation field on temporal trends of eculizumab consumption.
  
  
  RESULTS
  Eculizumab total consumption exceeded our estimate of the maximum on-label consumption since the end of 2011 and increased until the end of the study. The off-label consumption represented at least 50 % of the total consumption. The off-label consumption in organ transplantation also increased since 2011. The amount of publications grew through the study period, but overall, the evidence level remained low. Statistically, publications were neither associated with the drug consumption for transplantation in the long term nor in the short term.
  
  
  CONCLUSIONS
  Eculizumab started being notably used for off-label indications in France since the end of 2011, and this use increased until the end of the study. We found only low-level evidence concerning the off-label use of eculizumab in the transplantation field through the studied period.
authors.affiliation: APHP, Département d'Epidémiologie et Recherche Clinique CIC-EC 1425, Centre de Pharmacoépidémiologie (Cephepi), 75018, Paris, France. johann.castaneda@aol.fr.|University Paris Diderot, Sorbonne Paris Cité, Unité Mixte de Recherche (UMR) 1123: Epidémiologie clinique, évaluation économique et populations vulnérables (ECEVE), 75010, Paris, France. johann.castaneda@aol.fr.|Institut National de la Santé et de la Recherche Medicale (INSERM) CIC-EC 1425, Unité Mixte de Recherche (UMR) 1123: Epidémiologie clinique, évaluation économique et populations vulnérables (ECEVE), 75018, Paris, France. johann.castaneda@aol.fr.
authors.forename: Johann
authors.initials: J
authors.lastname: Castañeda-Sanabria
authors.affiliation: APHP, Département d'Epidémiologie et Recherche Clinique CIC-EC 1425, Centre de Pharmacoépidémiologie (Cephepi), 75018, Paris, France.|University Paris Diderot, Sorbonne Paris Cité, Unité Mixte de Recherche (UMR) 1123: Epidémiologie clinique, évaluation économique et populations vulnérables (ECEVE), 75010, Paris, France.|Institut National de la Santé et de la Recherche Medicale (INSERM) CIC-EC 1425, Unité Mixte de Recherche (UMR) 1123: Epidémiologie clinique, évaluation économique et populations vulnérables (ECEVE), 75018, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Hajage
authors.affiliation: Observatoire Des Médicaments, des dispositifs médicaux et de l'innovation thérapeutique (OMEDIT) Île-de-France, Paris, 75014, France.
authors.forename: Melisande
authors.initials: M
authors.lastname: Le Jouan
authors.affiliation: APHP, Hôpital Bichat, Département d'Information Médicale (DIM), 75018, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Perozziello
authors.affiliation: APHP, Département d'Epidémiologie et Recherche Clinique CIC-EC 1425, Centre de Pharmacoépidémiologie (Cephepi), 75018, Paris, France.|University Paris Diderot, Sorbonne Paris Cité, Unité Mixte de Recherche (UMR) 1123: Epidémiologie clinique, évaluation économique et populations vulnérables (ECEVE), 75010, Paris, France.|Institut National de la Santé et de la Recherche Medicale (INSERM) CIC-EC 1425, Unité Mixte de Recherche (UMR) 1123: Epidémiologie clinique, évaluation économique et populations vulnérables (ECEVE), 75018, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D004363:Drug Utilization / Q000706:statistics & numerical data; D005602:France; D016304:Hospitals, Private / Q000706:statistics & numerical data; D006779:Hospitals, Public / Q000706:statistics & numerical data; D006801:Humans; D056687:Off-Label Use / Q000706:statistics & numerical data*; D016377:Organ Transplantation; D009965:Orphan Drug Production / Q000706:statistics & numerical data*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab
keywords: Eculizumab; Off-label use; Organ rejection; Orphan drugs; Pharmaceutical spending; Transplantation