Review of indications for immunoglobulin (IG) use: Narrowing the gap between supply and demand.

Cellular blood components and plasma-derived medicinal products (PDMPs) are obtained from blood donated by volunteers. In a growing number of countries, in line with World Health Organization advice issued since the mid-1970s, donors are not remunerated. In recent decades, considerable efforts have been made to restrict the indications for labile blood components to those based on evidence, to ensure efficacy and safety. By contrast, the producers of PDMPs have developed pathogen reduction techniques for inactivating the microorganisms in (pooled) plasma, but little attention has been paid to the pertinence of the clinical indications for these products. The use of blood, and of erythrocytes in particular, has declined by almost 40%, but the use of immunoglobulins (IG) tripled between 2004 and 2018, making it necessary to pay donors to obtain sufficient blood to meet the market demand for these products. We analyzed the reasons for this increase to unsustainable levels of use, by investigating (practice) guidelines, recommendations, Cochrane data analyses and systematic reviews for clinical indications for IG over time. We found no new evidence explaining the huge increase up to 2018 or the predicted 5-7% yearly annual increase until 2024. For some former evidence-based indications, biologics have largely replaced IG, but the administration of IG for doubtful indications (up to 40%) has not decreased in recent decades. The main development since 2004 is that IG use in Europe has become market-driven rather than evidence-guided. As transfusion specialists and blood therapists, we must raise the alarm that this situation is likely to continue in the absence of good clinical studies determining the place of IG alongside other treatments, and for as long as market profitability remains the dominant driving force. We discuss here approaches for reversing this trend and moving towards European self-sufficiency through non-remunerated voluntary blood donation.