TOPIC 5: Manageability of therapy with mucoactive agents
Statement 8: Dornase Alfa therapy has important advantages in terms of handling and tolerability, with potential positive impact on therapeutic adherence.
The high consensus reached on this statement has to be correlated to the well-known tolerability profile of dornase alfa (Figure 4 ). In final consensus meeting, there was unanimous response to this statement.
Cystic fibrosis is a chronic and progressive disease and needs multiple life-long therapies that require daily and time-consuming administration. The treatment burden of CF raises the question of medication adherence.
Observational studies originating from registries confirmed that CF patients using dornase alfa benefit from its use and that the tolerability and safety profile of the drug in all age groups are good41. After completion of the Epidemiologic Registry of Cystic Fibrosis (ERCF) project, a comprehensive safety analysis of dornase alfa was performed. Emphasis was placed on infants and children under 5 years of age. The ERCF database contained data on 15,979 patients who were enrolled between 1994 and 2000. Twenty-eight out of 15,865 (0.18%) serious adverse events (SAEs) occurring during total ERCF follow up were classified by the participating clinics as possibly related to dornase alfa and most of these SAEs were typical complications of CF39. Patients under 5 years of age who were treated with dornase alfa experienced a similar frequency of adverse events resulting in hospitalization or other serious outcomes during treatment as in off-treatment periods41. These results indicate that CF patients under 5 years of age tolerate dornase alfa at least as well as older patients and support the evidence from previous RCTs that infants and young children may benefit from this therapy42,43.
In clinical practice, several factors contribute to a better management of dornase alfa therapy than therapy with hypertonic solution by CF patients. Indeed, dornase alfa is administered once a day and it is not necessary to perform a pre-use test or pharmacological protection which are required before administering other mucoactive agents. The onset of cough, which is very common with hypertonic solution and mannitol, is never reported during the use of dornase alfa. In addition, irritative symptoms are rare with dornase alfa and the drug is completely tasteless.
Good tolerability of dornase alfa therapy, minimum treatment burden and time requirement play more important roles in medication adherence44,45.