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.