Bas M Smits1, Ilona Kleine Budde2, Esther de Vries3,4, Ineke J M Ten Berge5, Robbert G M Bredius6, Marcel van Deuren7, Jaap T van Dissel8, Pauline M Ellerbroek9, Michiel van der Flier1,10, P Martin van Hagen11, Chris Nieuwhof12, Bram Rutgers13, Lieke E A M Sanders1, Anna Simon7, Taco W Kuijpers14, Joris M van Montfrans15. 1. Department of Pediatric Immunology and Infectious Diseases, UMC Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands. 2. Clinical Operations, Sanquin Plasma Products B.V, Amsterdam, The Netherlands. 3. Department of Tranzo, Tilburg School of Social and Behavioral Sciences, Tilburg University, Tilburg, The Netherlands. 4. Department of Jeroen Bosch Academy Research, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. 5. Department of Internal Medicine, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, The Netherlands. 6. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. 7. Department of Internal Medicine, Radboud UMC, Nijmegen, The Netherlands. 8. Department of Infectious Diseases, Leiden University Medical Centre, University of Leiden, Leiden, The Netherlands. 9. Division of Internal Medicine and Dermatology, Department of Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. 10. Pediatric Infectious Diseases and Immunology, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands. 11. Department of Internal Medicine/Immunology, Erasmus University Medical Centre, Rotterdam, The Netherlands. 12. Department of Allergology and Clinical Immunology, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands. 13. Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 14. Department of Paediatric Immunology and Infectious Diseases, Emma Children's Hospital, AUMC, University of Amsterdam, Amsterdam, The Netherlands. 15. Department of Pediatric Immunology and Infectious Diseases, UMC Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands. j.vanmontfrans@umcutrecht.nl.
Abstract
BACKGROUND: Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study. OBJECTIVE: To compare the efficacy of PA and IRT in a randomized crossover trial. METHODS: A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared. RESULTS: The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01). CONCLUSION: We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT. CLINICAL IMPLICATION: Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.
BACKGROUND: Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study. OBJECTIVE: To compare the efficacy of PA and IRT in a randomized crossover trial. METHODS: A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared. RESULTS: The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01). CONCLUSION: We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT. CLINICAL IMPLICATION: Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.
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