Immunoglobulin replacement therapy in primary immunodeficiency disorders: Pragmatic review and evidence mapping.

Background: Immunoglobulin replacement therapy (IgRT) is used in the treatment of patients with primary immunodeficiency disorders (PIDDs). There are some references to differences between preparations in terms of characteristics and efficacy, though comparative evidence is limited. Objectives: We sought to identify and map the evidence-base of clinical outcomes and adverse events of IgRT studies used for the treatment of patients with PIDDs and determine any signals of difference in treatment effect between different immunoglobulin brands. Methods: A pragmatic literature search was conducted in February 2023 to identify studies assessing the efficacy of IgRT in PIDDs, and an assessment of the feasibility of indirect treatment comparisons (ITC) was carried out. Annualized outcome data were presented in visualization plots and possible outlier results identified through naive (unanchored, unadjusted) comparisons; results were considered outliers when no overlap in confidence interval was identified. Results: After single-reviewer screening, 103 studies were included; 70 prospective studies were prioritized for extraction. A feasibility assessment found that ITC was not possible. Few outlier results for any particular commercial IgRT brand were identified across the outcomes considered, and those that were identified may have been due to differences in study methods or intervention characteristics rather than differing efficacy. Conclusions: Limited evidence on the comparative efficacy of different IgRT brands was identified. Reporting in studies of IgRT for PIDDs was found to vary widely, such that ITC was not possible. We recommend improving reporting to enable such comparisons in the future, including suggestions on improving or standardizing reporting of patient and study characteristics, outcome definitions, and follow-up duration and measures of variance.