Subcutaneous immunoglobulin for primary and secondary immunodeficiencies: an evidence-based review.

backgroundSubstitution with immunoglobulin can be administered intravenously (IV) or subcutaneously (SC) to patients with immunodeficiency, but it is not clear which route is to be preferred.

objectiveThe aim of this study was to compare IV and SC administration of immunoglobulin regarding efficacy, safety, health-related quality of life and health economics in patients with primary or secondary immunodeficiency.

methodPubMed and other databases were searched. Reference lists of retrieved articles were scanned and major immunoglobulin producers were contacted for additional articles. Randomized and non-randomized clinical studies that compared SC with IV immunoglobulin substitution in patients with immunodeficiency were included. The validity of the findings in the included studies was evaluated and summarized in accordance with the GRADE approach.

resultsTwenty-five studies were included; two randomized and 17 non-randomized studies of patients with primary immunodeficiency, one non-randomized study of patients with secondary immunodeficiency and five studies of health economics. The quality of evidence as assessed by the GRADE score was found to be moderate or low for all outcomes. Both IV and SC administration of immunoglobulin was found to be highly effective in preventing serious bacterial infections. IgG trough levels were higher with SC immunoglobulin substitution. Both therapy forms were concluded to be safe, as no serious adverse event was reported. Minor adverse events, consisting of local symptoms that were usually mild, were more frequent with SC immunoglobulin substitution. Health-related quality of life improved when patients switched from hospital-based IV immunoglobulin substitution to SC immunoglobulin substitution at home. The studies that evaluated health economics all found that SC administration was considerably more cost effective in comparison with IV immunoglobulin substitution. The main difference was that the number of lost work or school days was lower in patients with SC administration.

conclusionBoth SC and IV immunoglobulin substitution offer protection from serious bacterial infections and have good safety. On the basis of available studies it is not possible to rate one of the two substitution modes as superior to the other, at least not regarding efficacy and safety. Improvement of health-related quality of life with SC immunoglobulin substitution largely seems to be related to home therapy. Studies including patients with secondary immunodeficiency were few, as were randomized studies of patients with primary immunodeficiency.