Real-world patterns of Immunoglobulin Replacement Therapy for infection prevention in Common Variable Immunodeficiency: a multicenter nationwide study

Pedro Moral Moral^1,2*Victor Garcia-Bustos^1,3*Héctor Balastegui-Martín^1,2Sandra Martínez Mercader^1,3Carmen Bracke⁴Xavier Solanich^5,6,7Arnau Antolí^5,6,7Juan Luis Carrillo⁸Angel Robles-Marhuenda⁹Francesc Puchades¹⁰Ana Pelaez Ballesta¹¹Nuria López-Osle¹²Miguel Angel Torralba Cabeza¹³Ana María Bielsa Masdeu¹⁴Jorge Gil Niño¹⁵Nuria Tornador Gaya¹⁶Guillem Pascual Castellanos¹⁶Rosario Sánchez-Martínez¹⁷José Manuel Barragán-Casas¹⁸Andrés González-García¹⁹José Luís Patier de la Peña¹⁹Daniel López-Wolf²⁰Antonia Mora Rufete²¹Alba Canovas Mora²¹Marta Dafne Cabañero-Navalon^1,2

• ¹Primary Immunodeficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe, Valencia, Spain, Valencia, Spain
• ²Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe, Valencia, Spain, Valencia, Spain
• ³Severe Infection Research Group, Health Research Institute La Fe, Valencia, Spain, Valencia, Spain
• ⁴Infectious Diseases Service, Germans Trias i Pujol Hospital, Badalona; Fight Infections Foundation, Germans Trias i Pujol Hospital, Badalona, Badalona, Spain
• ⁵Adult Primary Immunodefciency Unit (UFIPA), Internal Medicine Deparment, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain, Barcelona, Spain
• ⁶The Systemic, Vascular Diseases and Ageing Group. Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain, Barcelona, Spain
• ⁷Clinical Sciences Department, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain, Barcelona, Spain
• ⁸Department of Internal Medicine, Virgen de la Victoria University Hospital, Málaga, Spain, Málaga, Spain
• ⁹Department of Internal Medicine, La Paz University Hospital, Madrid, Madrid, Spain, Madrid, Spain
• ¹⁰Department of Internal Medicine, University General Hospital of Valencia, Valencia, Spain, Valencia, Spain
• ¹¹Department of Internal Medicine, Rafael Méndez University Hospital, Murcia, Spain, Murcia, Spain
• ¹²Department of Internal Medicine, Cruces University Hospital, Bizkaia, Spain, Bizkaia, Spain
• ¹³Unit for Rare Diseases, Internal Medicine Service, Lozano Blesa University Hospital, Zaragoza, Zaragoza, Spain
• ¹⁴Department of Internal Medicine, Miguel Servet University Hospital, Zaragoza, Spain, Zaragoza, Spain
• ¹⁵Immunodeficiencies clinic, Internal Medicine Department, 12 de Octubre Hospital, Madrid, Madrid, Spain
• ¹⁶Department of Internal Medicine, University General Hospital of Castellón, Castellón, Spain, Castellón, Spain
• ¹⁷Internal Medicine Department, Dr. Balmis General University Hospital, ISABIAL, Alicante, Spain, Alicante, Spain
• ¹⁸Department of Internal Medicine, Complejo Asistencial de Ávila, Ávila, Spain, Ávila, Spain
• ¹⁹Systemic Autoimmune Diseases Unit, Internal Medicine Service, Ramón y Cajal Hospital, IRYCIS, Madrid, Madrid, Spain
• ²⁰Department of Internal Medicine, University Hospital Alcorcón Foundation, Madrid, Spain, Madrid, Spain
• ²¹Department of Internal Medicine, General University Hospital of Elche, Alicante, Spain, Alicante, Spain

Background and aims: Immunoglobulin replacement therapy (IgRT), administered intravenously (IVIg) or subcutaneously (SCIg), is the cornerstone treatment for patients with Common Variable Immunodeficiency (CVID). Although both modalities demonstrate similar efficacy, SCIg is associated with fewer systemic adverse events and increased patient autonomy. Despite these advantages, its utilization remains limited in certain regions, particularly in the Mediterranean region. This study aimed to evaluate real-world patterns of IgRT use in Spanish CVID patients and provide a comprehensive analysis of the factors associated with IVIg and SCIg administration in routine clinical practice. Methods: A cross-sectional, multicenter study was conducted using data from the GTEM-SEMI-CVID Registry, encompassing 212 adult CVID patients receiving IgRT across Spain. Patients were grouped based on the administration route: IVIg and SCIg. Demographic, clinical, and immunological data, including IgRT modality, dosage, administration setting, and comorbidities, were collected. Comparative statistical analyses were performed to identify differences between both treatment groups. Results: Of the 212 patients, 58.5% received IVIg and 41.5% received SCIg. SCIg recipients were younger (47.5 vs. 54.8 years, p = 0.003) and predominantly treated at home (80.6% vs. 1.6%, p < 0.001), compared to those receiving IVIg. SCIg use was significantly higher in tertiary hospitals compared to secondary ones (44.4% vs. 17.4%, p = 0.0136). Infection rates, autoimmune comorbidities, weekly doses (7.2 g for IVIg vs. 7.7 g for SCIg, p = 0.142), and IgG trough levels were comparable across groups. Conclusion: This study provides real-world evidence on IgRT patterns in Spanish patients with CVID, revealing a marked increase in SCIg use over the past decade, although IVIg remains predominant, especially in secondary hospitals. Age significantly influenced the choice of modality, with IVIg preferred for older patients and SCIg for younger ones, while disease severity did not impact this decision. These findings underscore the need to optimize access to SCIg, particularly in secondary centers, to enhance patient autonomy and improve therapeutic outcomes.