Kalydeco治疗囊性纤维化的效果怎么样

Kalydeco has a remarkable effect in treating cystic fibrosis. It is the first drug that can affect the intrinsic cause of cystic fibrosis. It is suitable for patients with rare cystic fibrosis aged 6 years and above who have a specific G551D mutation in the cystic fibrosis transmembrane transduction regulator (CFTR) gene. Kalydeco is a pill that treats patients with the G551D mutation, which helps the CFTR gene function better to make proteins, thereby improving patients' lung function and other problems caused by CF, such as increasing weight gain.

Kalydeco trial for cystic fibrosis

Demonstrated clinical benefit in cystic fibrosis patients with G551D-CFTR mutations and reduced lung function. In the increasing number of children and young adults with cystic fibrosis who have normal vital capacity, the lung clearance index (LCI) using multiple breath flushes may be an alternative and more sensitive method than forced expiratory volume in 1 s (FEV1) to assess treatment response. The purpose of this study is to evaluate Kalydeco in patients with cystic fibrosis, G551D-CFTR mutation, and LCI with FEV1 >90% predicted.

Test method

This phase 2, multicenter, placebo-controlled, double-blind 2×2 crossover study (NCT01262352) was conducted in patients with cystic fibrosis with at least one G551D-CFTR allele with a predicted FEV1 >90%. Patients must also have an LCI above 7.4 at screening, be 6 years or older, and weigh 15kg or more.

Eligible patients were randomly assigned to receive one of two treatment sequences (placebo followed by Kalydeco 150 mg twice daily [Sequence 1] or Kalydeco 150 mg followed by placebo [Sequence 2]) for 28 days per cycle, with a 28-day washout between treatment periods.

Research results

A total of 21 patients were enrolled, 11 of whom were assigned to the sequence 1 group and 10 to the sequence 2 group. Twenty patients received treatment, and 17 patients completed the trial (8 patients in the sequence 1 group and 9 patients in the sequence 2 group). There was a significant improvement in LCI with Kalydeco treatment compared with placebo (mean difference in change from baseline between groups at Days 15 and 29, -2.16 [95% CI -2.88 to -1.44]; p<0.0001).

Test conclusion

Kalydeco improved LCI in cystic fibrosis patients aged 6 years or older who had at least one G551D-CFTR allele. LCI may be a more sensitive surrogate for FEV1 to detect response to intervention in these patients with mild lung disease.

Kalydeco side effects

Common symptoms of Kalydeco include headache, upper respiratory tract infection, nasal congestion, nausea, rash, rhinitis, dizziness, joint pain, and bacteria in sputum. Patients have different physiques and conditions, and the side effects after taking the drug are also different. However, the safety of Kalydeco is usually relatively tolerable.

Recommended related articles:

References

Davies J, Sheridan H, Bell N, Cunningham S, Davis SD, Elborn JS, Milla CE, Starner TD, Weiner DJ, Lee PS, Ratjen F. Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a randomized controlled trial. Lancet Respir Med. 2013 Oct;1(8):630-638. doi: 10.1016/S2213-2600(13)70182-6. Epub 2013 Sep 10. Erratum in: Lancet Respir Med. 2017 Jul;5(7):e26. PMID: 24461666.