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.

Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies / Milito, Cinzia; Pulvirenti, Federica; Cinetto, Francesco; Lougaris, Vassilios; Soresina, Annarosa; Pecoraro, Antonio; Vultaggio, Alessandra; Carrabba, Maria Cristina; Lassandro, Giuseppe; Plebani, Alessandro; Spadaro, Giuseppe; Matucci, Andrea; Fabio, Giovanna; Dellepiane, Rosa Maria; Martire, Baldassarre; Agostini, Carlo; Abeni, Damiano; Tabolli, Stefano; Quinti, Isabella. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - ISSN 0091-6749. - 144:2(2019), pp. 584-593. [10.1016/j.jaci.2019.01.051]

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

Milito, Cinzia;Pecoraro, Antonio;CARRABBA, Maria Cristina;Spadaro, Giuseppe;
2019

Abstract

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.
2019
Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies / Milito, Cinzia; Pulvirenti, Federica; Cinetto, Francesco; Lougaris, Vassilios; Soresina, Annarosa; Pecoraro, Antonio; Vultaggio, Alessandra; Carrabba, Maria Cristina; Lassandro, Giuseppe; Plebani, Alessandro; Spadaro, Giuseppe; Matucci, Andrea; Fabio, Giovanna; Dellepiane, Rosa Maria; Martire, Baldassarre; Agostini, Carlo; Abeni, Damiano; Tabolli, Stefano; Quinti, Isabella. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - ISSN 0091-6749. - 144:2(2019), pp. 584-593. [10.1016/j.jaci.2019.01.051]
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0091674919303884-main.pdf

solo utenti autorizzati

Tipologia: Documento in Post-print
Licenza: Dominio pubblico
Dimensione 1.84 MB
Formato Adobe PDF
1.84 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/752256
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 51
  • ???jsp.display-item.citation.isi??? 44
social impact