Predicting response to rhDNase and hypertonic saline in children with cystic fibrosis

Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). Alternate-day rhDNase and hypertonic saline (HS) represent potential cheaper alternative therapies. However, not all patients improve on treatment. To assess response, many CF centers have developed formal n-of-1 trials of treatment to find out who benefits. Response to daily rhDNase at 3 months has been shown to be a good predictor of response at 1 year. There are no data correlating individual response at a shorter time period with 3-month response. We assessed whether individual responses to daily rhDNase, alternate-day rhDNase, and HS could be predicted from lung function response at 6 weeks, thus shortening the n-of-1 trial, or from baseline patient characteristics, therefore avoiding the need for an n-of-1 trial. In a randomized crossover trial, 48 CF children were allocated consecutively to 12 weeks of once-daily 2.5-mg rhDNase, alternate-day 2.5-mg rhDNase, and twice-daily 5 ml of 7% HS. Forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) were measured at baseline and then at 6 and 12 weeks into each treatment period. Lung function response to the drugs at 6 weeks was highly predictive of response at 3 months. There was some evidence that response to HS was worse in patients with lower baseline lung function. However, there was no association between response to alternate-day or daily rhDNase and baseline characteristics. In conclusion, response to rhDNase and HS at 6 weeks was highly predictive of response at 3 months. For daily and alternate-day rhDNase, at least, the drug needs to be administered for at most 6 weeks initially to assess long-term response to treatment. Response to treatment could not be reliably predicted from baseline characteristics.