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

Pediatr Pulmonol. 2004 Apr;37(4):305-10. doi: 10.1002/ppul.10442.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Cross-Over Studies
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Deoxyribonuclease I / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Forced Expiratory Volume / physiology
  • Humans
  • Male
  • Nebulizers and Vaporizers*
  • Predictive Value of Tests
  • Recombinant Proteins / therapeutic use*
  • Saline Solution, Hypertonic / therapeutic use*
  • Vital Capacity / physiology

Substances

  • Recombinant Proteins
  • Saline Solution, Hypertonic
  • DNASE1 protein, human
  • Deoxyribonuclease I