Immunoglobulin Replacement Therapy Versus Antibiotic Prophylaxis as Treatment for Incomplete Primary Antibody Deficiency

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.

Evaluation and treatment of rhinosinusitis with primary antibody deficiency in adults: Evidence‐based review with recommendations

“…In a large cohort study of CVID patients by Lucas et al. in 2010, a subset of 18 patients with CVID who received prophylactic antibiotics over a period of 3 months were analyzed 68 . Only three patients showed improvement in the rate of infections 68 .…”

“…in 2010, a subset of 18 patients with CVID who received prophylactic antibiotics over a period of 3 months were analyzed 68 . Only three patients showed improvement in the rate of infections 68 . However, there are no published studies that directly evaluated the clinical efficacy and effectiveness of antibiotic prophylaxis in specifically CRS or RARS with PAD.…”

Bronchiectasis and obstructive lung diseases in primary antibody deficiencies and beyond: update on management and pathomechanisms

“…In patients with bronchiectasis and milder PAD, treatment should start with prophylactic antibiotics first [37]. Macrolide antibiotics are known to express antimicrobial and anti-inflammatory properties and three large randomized controlled trials showed a reduction in exacerbation frequency in patients with bronchiectasis [38][39][40].…”

“…In patients developing more than three exacerbations and/or infections of the lower respiratory tract requiring antibiotic treatment despite optimized IgG levels, prophylactic antibiotics may be essential. In patients with bronchiectasis and milder PAD, treatment should start with prophylactic antibiotics first [37]. Macrolide antibiotics are known to express antimicrobial and anti-inflammatory properties and three large randomized controlled trials showed a reduction in exacerbation frequency in patients with bronchiectasis [38–40].…”

Effectiveness of low-dose intravenous immunoglobulin therapy in minor primary antibody deficiencies: A 2-year real-life experience

“…UAD encompasses a wide group of patients showing more severe serum Ig reduction without fulfilling CVID or other PID criteria. Guidelines for treatment of IgGSD and UAD are lacking, even if prophylactic antibiotic treatment and immunoglobulin replacement therapy (IRT) have been used [6,7]. Milder PADs have been less extensively studied; however, their prevalence in patients with obstructive lung disease and bronchiectasis is probably underestimated and carries a significant burden of disease [5,8,9].…”