European Journal of Clinical Pharmacology

, Volume 72, Issue 6, pp 737–746 | Cite as

Off-label use of the expensive orphan drug eculizumab in France 2009–2013 and the impact of literature: focus on the transplantation field

  • Johann Castañeda-SanabriaEmail author
  • David Hajage
  • Melisande Le Jouan
  • Anne Perozziello
  • Florence Tubach
Pharmacoepidemiology and Prescription



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.


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.


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.


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.


Eculizumab Off-label use Orphan drugs Transplantation Organ rejection Pharmaceutical spending 



Author contributions

Dr. J. Castaneda-Sanabria had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Castaneda-Sanabria, Hajage and Tubach are responsible for the study concept and design. Acquisition of the data was performed by Le Jouan, Perozziello and Castaneda-Sanabria. Castaneda-Sanabria, Perozziello, Hajage and Tubach analysed and interpreted the data. Castaneda-Sanabria drafted the manuscript. Critical revision of the manuscript for important intellectual content was performed by Hajage, Le Jouan, Perozziello and Tubach. Statistical analysis was performed by Castaneda-Sanabria, Hajage and Perozziello. Tubach and Hajage supervised the study.

Financial disclosure

This study was financed by the National Institute for Health and Medical Research (Inserm) Clinical Research and Clinical Epidemiology Center (CIC-EC) 1425 as a part of a research internship. This institution did not have any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript.

Previous presentations of the work

This work was partly presented as an oral communication at the 9th annual French speaking conference of clinical epidemiology (Epiclin) in Montpellier, France, April 20–22, 2015.

Compliance with ethical standards

Competing interest

All authors declare that they do not have any financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years and any other relationships or activities that could appear to have influenced the submitted work.

Supplementary material

228_2016_2027_MOESM1_ESM.pdf (444 kb)
ESM 1 (PDF 444 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Johann Castañeda-Sanabria
    • 1
    • 2
    • 3
    Email author
  • David Hajage
    • 1
    • 2
    • 3
  • Melisande Le Jouan
    • 4
  • Anne Perozziello
    • 5
  • Florence Tubach
    • 1
    • 2
    • 3
  1. 1.APHP, Département d’Epidémiologie et Recherche Clinique CIC-EC 1425Centre de Pharmacoépidémiologie (Cephepi)ParisFrance
  2. 2.University Paris Diderot, Sorbonne Paris CitéUnité Mixte de Recherche (UMR) 1123: Epidémiologie clinique, évaluation économique et populations vulnérables (ECEVE)ParisFrance
  3. 3.Institut National de la Santé et de la Recherche Medicale (INSERM) CIC-EC 1425Unité Mixte de Recherche (UMR) 1123: Epidémiologie clinique, évaluation économique et populations vulnérables (ECEVE)ParisFrance
  4. 4.Observatoire Des Médicaments, des dispositifs médicaux et de l’innovation thérapeutique (OMEDIT) Île-de-FranceParisFrance
  5. 5.APHP, Hôpital BichatDépartement d’Information Médicale (DIM)ParisFrance

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