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

The orphan drug eculizumab (Soliris A (R)) 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.