A first-year dornase alfa treatment impact on clinical parameters of patients with cystic fibrosis: the Brazilian cystic fibrosis multicenter study

Abstract

OBJECTIVE: To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF) patients. METHODS: The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0), and at six (T2) and 12 (T4) months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years. Pulmonary tests, airway microbiology, emergency room visits, hospitalizations, emergency and routine treatments were evaluated. Student's t-test, chi-square test and analysis of variance were used when appropriated. RESULTS: Routine treatments were based on respiratory physical therapy, regular exercises, pancreatic enzymes, vitamins, bronchodilators, corticosteroids, and antibiotics. In the six months prior the study (T0 phase), hospitalizations for pulmonary exacerbations occurred in 38.0, 10.0 and 61.4% in the three age groups, respectively. After one year of intervention, there was a significant reduction in the number of emergency room visits in the six to 11 years group. There were no significant changes in forced expiratory volume in one second (VEF1), in forced vital capacity (FVC), in oxygen saturation (SpO2), and in Tiffenau index for all age groups. A significant improvement in Shwachman-Kulczychi score was observed in the older group. In the last six months of therapy, chronic or intermittent colonization by P. aeruginosa was detected in 75.0, 71.4 and 62.5% of the studied groups, respectively, while S. aureus colonization was identified in 68.6, 66.6 and 41.9% of the cases. CONCLUSIONS: The treatment with dornase alfa promoted the maintenance of pulmonary function parameters and was associated with a significant reduction of emergency room visits due to pulmonary exacerbations in the six to 11 years age group, with better clinical scores in the >14 age group, one year after the intervention.

Neutrophil extracellular traps are associated with inflammation in chronic airway disease

“…Regulating neutrophil activation may therefore aid in reducing NETs, and targeted removal of excessive airway NETs may be a novel treatment option. Indeed, targeted treatment of NETs with human recombinant DNase I (Dornase alfa) has shown benefit in reducing exacerbations and lung function preservation in CF …”

Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association)

“…We selected 32 studies, 17 , 131 - 161 18 of which were RCTs that compared the use of dornase alfa with placebo, 17 , 131 - 135 , 140 - 142 , 144 , 145 , 149 , 151 - 154 , 159 , 160 and 14 were observational studies, 136 - 139 , 143 , 146 - 148 , 150 , 155 - 158 , 161 as illustrated in and .…”

A Systematic Review and Meta-Analysis of Enzyme Replacement Therapy in Late-Onset Pompe Disease

“…These outcomes were QOL, functional capacity (6MWT, forced vital capacity (FVC), and Walton and Gardner-Medwin Scale (WGMS) score), survival, TOV in hours/day, muscle strength, sleep quality, swallowing, and safety. For FVC, an increase of at least 10% after the intervention was considered a clinically relevant improvement [ 16 , 17 ]. For 6MWT, an increase of at least 26 m was considered a clinically significant change, as recommended by Schrover et al for muscular diseases [ 18 ].…”