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

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Background

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.

Objective

We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs.

Methods

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.

Results

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.

Conclusion

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.

Key words

Primary antibody defects
azithromycin
antibiotic prophylaxis
respiratory exacerbation
chronic obstructive pulmonary disease

Abbreviations used

AE
Adverse event
CF
Cystic fibrosis
COPD
Chronic obstructive pulmonary disease
CVID
Common variable immunodeficiency
HR
Hazard risk
HRQoL
Health-related quality of life
PAD
Primary antibody deficiency
PID
Primary immunodeficiency disease
SF-36
Short Form 36
SGRQ
Saint George Respiratory Questionnaire
XLA
X-linked agammaglobulinemia

Cited by (0)

Clinical Trials no. EUDRACT 2011-004351-39 was funded by the Agenzia Italiana del Farmaco (AIFA). The Rome PID Clinical Research Center is supported by the Jeffrey Modell Foundation.

Disclosure of potential conflict of interest: A. Pecoraro and I. Quinti have received consultation fees and grants from Shire, CSL Behring, Octapharma, and Kedrion. A. Matucci and C. Agostini have received consultation fees by Shire, Roche, CSL Behring, Octapharma, and Novartis. The rest of the authors declare that they have no relevant conflicts of interest.

Clinical Trials no. EUDRACT 2011-004351-39.

These authors contributed equally to this work.