Abstract
PURPOSE: Despite well-conducted replacement therapy with polyvalent immunoglobulins (IgRT), some patients with primary immunodeficiencies (PID) continue to experience recurrent or chronic infections. IgA and IgM, essential for mucosal and complement-mediated immunity, are absent or minimal in standard immunoglobulin products. The aim of this study is to evaluate the safety and clinical evolution profiles in PID patients with undetectable IgA/IgM levels and persistent infections despite standard IgRT, after introduction of an IgA- and IgM-enriched immunoglobulin preparation (IgGAM, Pentaglobin(®)). METHODS: A compassionate use program (CUP) in France enrolled 20 PID patients with undetectable IgA/IgM levels, receiving IgGAM IV infusions every 7-14 days. Tolerance, infection frequency, hospitalizations, and biological markers (Ig levels, complement activation, salivary IgA) were analyzed prospectively. RESULTS: Twenty patients were included in the CUP at the time of analysis. No severe adverse event was reported. Half of the patients experienced mild to moderate hypersensitivity symptoms. Mean antibiotic courses dropped from 5.4 to 2.3/year (p = 0.0009) and mean number of hospitalizations decreased from 2.6 to 1.2/year (p = 0.01). Median serum IgA and IgM levels increased three months after IgGAM start. IgM and low levels of IgA were detected in saliva samples, suggesting at least a transient transfer of IgA/IgM from IgGAM into mucosal fluids. CONCLUSION: In patients with severe PID and undetectable IgA/IgM, IgGAM was associated with reduced infections and hospitalizations. Controlled studies are needed to confirm the benefit of IgA/M enriched immunoglobulin preparations in PID patients with persistent and/or recurrent respiratory or digestive infections.