Utilization of intravenous or subcutaneous immunoglobulins in secondary immune deficiency (ULTIMATE): A retrospective multicenter study.

INTRODUCTION: We conducted a retrospective multicenter cohort study of patients receiving Immunoglobulin replacement therapy (IgRT) for secondary immune deficiency (SID) during 2012. METHODS: Data were retrospectively collected from the first dose of Ig administered in 2012 to 1 year afterward in terms of the indication for IgRT, as well as efficacy and safety. RESULTS: In total, 16 hospitals participated in the study, and 368 patients were included. Indications for IgRT were non-Hodgkin lymphoma (82 [22.3%] patients), multiple myeloma (76 [20.7%]), chronic lymphocytic leukemia (64 [17.4%]) and other (79 [21.5%]). Only 89 (24.2%) patients received IgRT according to 2011 European Medical Agency (EMA) recommendations; 196 (53.3%) received prophylactic antibiotics and 262 (76.2%) had an IgG level < 4 g/L before IgRT initiation. CONCLUSION: In this study, whatever the criteria, only 24.2% of patients with SID who received IgRT met EMA recommendations, which suggests a misuse of IgRT in SID.

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

PURPOSE: 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. CONCLUSION: 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.

Budget Impact Analysis of Fixed Dose Versus Weight-Based Dosing Regimen of Nivolumab and Pembrolizumab in the Treatment of Non-Small Cell Lung Cancer.

In 2018, dosing regimens of the two most prescribed immune check point inhibitors (ICI), nivolumab (Opdivo®) and pembrolizumab (Keytruda®), in the treatment of lung cancer were changed from weight-based dosing to fixed dosing. The aim of this study was to compare the economic impact of this change in our university hospital group and then across Ile-de-France, the most inhabited French region. A budget impact analysis (BIA) has been performed on the French public health insurance data. The duration of treatment and the weight of the patients were calculated using data from the patients treated at our health facility and from clinical studies. The cost of treatment was calculated at the local level of our health facility and then for Ile-de-France. Our model demonstrates an additional cost of €550,115 in our hospital and €9,704,778 in Ile-de-France for a fixed dose prescription in 2018. In 2019, the BIA concluded an additional cost, according to the respective low and high assumptions, of €556,969 and €756,544 locally and € 10,201,027 to €14,486,141 for Ile-de-France for an equivalent efficacy between the two different drug dosing regimens of nivolumab and pembrolizumab. The adoption of the fixed dose regimen would lead, according to the least expensive hypothesis, to an additional cost of 26% for the ICI. These results encourage reflection on the strict adoption of this dosage modification. The option of maintaining the free choice between a prescription adapted to weight or in a fixed dose seems a relevant option and should be considered.