Pedro Moral Moral ^1,2 Marta Dafne Cabanero-Navalon ^1,2* Paula López León ^1,2 Héctor Balastegui-Martín ^1,2 Sandra Martínez Mercader ^1,2 Amparo Mir ³ Victor Garcia-Bustos ^1,4,5

• ¹ Primary Immunodeficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe, Valencia, Spain
• ² Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe, Valencia, Spain
• ³ University of Valencia, Central Research Unit, Valencia, Spain
• ⁴ Severe Infection Research Group, Health Research Institute La Fe, Valencia, Spain
• ⁵ Unit of Infectious Diseases, University and Polytechnic Hospital La Fe, Valencia, Spain

Immunoglobulin replacement therapy (IgRT), either intravenous (IVIg) or subcutaneous (SCIg), is crucial for managing primary immune deficiencies (PIDs) with hypogammaglobulinemia by reducing infection rates and mortality. During the COVID-19 pandemic, a global shortage of SCIg prompted our unit to reduce SCIg doses or maintain the same dose intravenously. This study evaluates the impact of a standardized SCIg dose reduction on infection rates and clinical outcomes in patients with humoral PID and with a low burden of infections. Adult PID patients on SCIg for at least 6 months, with IgG trough levels ≥ 700 mg/dL (or ≥ 900 mg/dL under specific conditions), and no significant infections in the past 6 months were eligible. A dose reduction of 15 mg/kg/week (60 mg/kg/month) for every 150 mg/dL above 700 mg/dL (or 900 mg/dL) was proposed. Clinical and laboratory data, and infectious events at 6-and 12-month follow-ups, were analyzed. Thirty-one patients with PID were included: common variable immunodeficiency (54.83%), IgG subclass deficiency (9.67%), and other PIDs (35.48%). The average SCIg dose was initially reduced from 7.82 g/week to 5.72 g/week and adjusted to 6.94 g/week at 12 months. There was no significant change in severe or mild infections before and at 6-and 12-months post-dose adjustment. The dose reduction saved an average of 5,550 euros per patient annually, totaling 172,050 euros annually for our cohort. Thus, optimizing SCIg doses in selected well-controlled humoral PIDs is feasible without increasing infection rates, conserving this plasma-derived product during shortages. Larger prospective studies are needed to confirm this strategy's utility and its application to other Ig formulations.