Immunoglobulin replacement therapy (IVIg and SCIG) is a cornerstone of care for patients with primary immunodeficiency (PID), markedly reducing severe infections and improving quality of life. However, mounting global demand, intermittent supply constraints, and rising costs have underscored the need for sustainable, evidence-based approaches to dosing and delivery. At the same time, heterogeneity in patient phenotypes, comorbidities, and pharmacokinetics contributes to variable clinical responses, highlighting critical gaps in our understanding of how to personalize therapy. Advances in pharmacometric modeling, real-world data analytics, and biomarker discovery, alongside innovations in formulation, delivery devices, and home-based care, now offer new opportunities to refine immunoglobulin use. A balanced framework that integrates clinical efficacy, patient-centered outcomes, and resource stewardship is urgently needed.

The goal of this Research Topic is to define practical, data-driven strategies for optimizing immunoglobulin replacement therapy in PID across the full continuum of care. We aim to clarify how dose, route, frequency, and product selection influence infection risk, immune reconstitution, and patient-reported outcomes; to illuminate mechanistic and clinical determinants of differential response; and to identify approaches that enhance access and sustainability without compromising safety or effectiveness. By integrating mechanistic, translational, and health-services perspectives, this collection seeks to generate guidance that is both clinically actionable and adaptable across diverse healthcare settings.

We welcome Original Research, Review, Mini Review, and Perspective articles spanning, but not limited to:

- Strategies for dose optimization (e.g., individualized trough targets, AUC-based dosing, PK/PD-informed approaches) and their impact on infections, hospitalizations, and quality of life;

- Comparative effectiveness of IVIg versus SCIG, flexible dosing schedules, and hybrid regimens; transition protocols between routes ;

- Innovations in administration: home infusion models, rapid- and facilitated-infusion protocols, device advances, and patient training/education;

- Safety profiles, adverse event mitigation, and risk stratification (e.g., thromboembolic risk, hemolysis, aseptic meningitis);

- Determinants of variable response, including genetic and immunologic biomarkers, microbiome influences, and comorbid conditions;

- Resource stewardship: cost-effectiveness analyses, formulary strategies, and policy frameworks during periods of high demand or limited supply;

- Real-world evidence and registry-based insights into utilization trends, outcomes during high-risk seasons, and resilience during shortages;

- Alternative and adjunctive therapies (e.g., prophylactic antimicrobials, monoclonal antibodies), and their integration with or substitution for immunoglobulin in select contexts;

- Special populations and life-course considerations: pediatric-to-adult transitions, pregnancy, elderly patients, and complex phenotypes;

- Standardization of outcome measures, patient-reported outcomes, and best practices for guideline development and implementation.

Are you interested in contributing a manuscript to this Research Topic?

Optimizing Immunoglobulin Therapy in Primary Immunodeficiency