239 General Discussion nantly from the United States, shortages are a continual problem.27 There is a need to bring strategies for European self-sufficiency and governance for appropriate use, which has resulted in various initiatives, both at the regional, national, and international level. In Europe, the SUPPLY project was conducted in 2022-2023 to increase and strengthen the resilience of plasma collection in Europe to enable a stable and adequate supply of plasma-derived medicinal products (PDMPs) by assessing the entire plasma value chain, from donor recruitment to demand and use of PDMPs.28 Sanquin was a key participant within SUPPLY and had members in multiple Work Packages. I participated in Work Package 6 of the SUPPLY project, to assess the appropriate use of Ig at baseline and its prioritization in times of crisis, which enabled understanding of the interconnections of these transformational factors and the existing gaps. One underlying issue is the need for more evidence. Since Ig is used both for replacement and immunomodulatory therapies, there is evidence proving the efficacy for “on-label” (approved) usage but little concerning “off-label” usage. This requires more quality evidence to legitimize Ig usage; while RCTs should be done, these are often not feasible to do for very rare diseases. Therefore, the use of Real-World Evidence needs to be considered instead. Concurrently, further evidence is needed to understand optimal dosage and length of treatment, including how to taper (periodically reduce) or withdraw Ig treatment. This is necessary especially in neurology, which is the top consumer of Ig, and where several clinical studies have begun.29– 31 Additionally, evidence on understanding Ig’s mechanism of action is crucial. Work on IgG (a)fucosylation32 is pioneering understanding of such mechanisms and contributing towards alternative therapies, such as FcRn inhibitors which have shown to be effective for Myasthenia Gravis33 and are likely to reduce IVIg use in autoimmune and alloimmune diseases.32,34 Excitingly, VYVGART® Hytrulo is the first and only FcRn inhibitor that has been approved by the FDA for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP),35 a neurological indication that continually absorbs a significant amount of the market.36–38 Secondly, there is a need for improved management and monitoring. The SUPPLY interview results of European clinicians and pharmacists showed that mitigating measures were taken in response to varying levels of shortages.39 From these interviews, two mitigating measures reported were: (1) how treatment paradigms were amended so that Ig was not the first-line treatment option, and (2) how hospitals that previously did not have a system of authorization/checkpoints for Ig approval implemented one. Within a management plan for Ig, a system of checkpoints (involving multiple steps of Ig approval), a coordinated communication and shortage awareness system, and alignment of existing clinical guidelines, should be in place. The UK is exemplary
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