Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies

• Published in: Journal of allergy and clinical immunology 2019-08, Vol.144 (2), p.584-593.e7
• Main Authors: Milito, Cinzia, Pulvirenti, Federica, Cinetto, Francesco, Lougaris, Vassilios, Soresina, Annarosa, Pecoraro, Antonio, Vultaggio, Alessandra, Carrabba, Maria, Lassandro, Giuseppe, Plebani, Alessandro, Spadaro, Giuseppe, Matucci, Andrea, Fabio, Giovanna, Dellepiane, Rosa Maria, Martire, Baldassarre, Agostini, Carlo, Abeni, Damiano, Tabolli, Stefano, Quinti, Isabella
• Format: Article
• Language: English
• Subjects: Adult; antibiotic prophylaxis; Antibiotics; Asthma; Azithromycin; Azithromycin - administration & dosage; Azithromycin - adverse effects; Chronic infection; Chronic obstructive pulmonary disease; Clinical trials; Cystic fibrosis; Diaries; Dose-Response Relationship, Drug; Double-Blind Method; Double-blind studies; Family medical history; Female; Haemophilus Infections - immunology; Haemophilus Infections - prevention & control; Haemophilus influenzae - immunology; Humans; Immunoglobulins; Immunology; Infections; Inheritances; Laboratories; Lung diseases; Male; Middle Aged; Oral administration; Patients; Physicians; Pneumonia, Pneumococcal - immunology; Pneumonia, Pneumococcal - prevention & control; Primary antibody defects; Primary Immunodeficiency Diseases; Prophylaxis; Questionnaires; Respiratory diseases; respiratory exacerbation; Respiratory tract; Respiratory tract diseases; Safety; Streptococcus infections; Streptococcus pneumoniae - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2019.01.051

Lacking protective antibodies, patients with primary antibody deficiencies (PADs) experience frequent respiratory tract infections, leading to chronic pulmonary damage. Macrolide prophylaxis has proved effective in patients with chronic respiratory diseases. We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs. We designed a 3-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250 mg administered once daily 3 times a week for 2 years) would reduce respiratory exacerbations in patients with PADs and chronic infection–related pulmonary diseases. The primary end point was the number of annual respiratory exacerbations. Secondary end points included time to first exacerbation, additional antibiotic courses, number of hospitalizations, and safety. Eighty-nine patients received azithromycin (n = 44) or placebo (n = 45). The number of exacerbations was 3.6 (95% CI, 2.5-4.7) per patient-year in the azithromycin arm and 5.2 (95% CI, 4.1-6.4) per patient-year in the placebo arm (P = .02). In the azithromycin group the hazard risk for having an acute exacerbation was 0.5 (95% CI, 0.3-0.9; P = .03), and the hazard risk for hospitalization was 0.5 (95% CI, 0.2-1.1; P = .04). The rate of additional antibiotic treatment per patient-year was 2.3 (95% CI, 2.1-3.4) in the intervention group and 3.6 (95% CI, 2.9-4.3) in the placebo group (P = .004). Haemophilus influenzae and Streptococcus pneumoniae were the prevalent isolates, and they were not susceptible to macrolides in 25% of patients of both arms. Azithromycin's safety profile was comparable with that of placebo. The study reached the main outcome centered on the reduction of exacerbation episodes per patient-year, with a consequent reduction in additional courses of antibiotics and risk of hospitalization. [Display omitted]