Taylor-Cousar JL, et al. - In a study population comprising patients with cystic fibrosis (CF) with severe lung disease, researchers assessed the safety, tolerability, and efficacy of lumacaftor/ivacaftor. They noted that respiratory events were more common in patients with higher lung function vs in patients with percent predicted forced expiratory volume in 1 second (ppFEV₁) < 40; aside from these events, the lumacaftor/ivacaftor safety profile was consistent with previous studies. For patients with ppFEV₁ < 40, treatment initiation at a lower dose with augmented monitoring before increasing to the full dose may be beneficial.

Methods

• An open-label, prospective study was conducted, wherein, patients with CF, 12 years of age and older, homozygous for F508del-CFTR, with percent predicted forced expiratory volume in 1 second (ppFEV1) < 40 received lumacaftor 400 mg/ivacaftor 250 mg every 12 h (full dose) for 24 weeks.
• Dose modification to half dose for 1–2 weeks (including at initiation) was permitted.
• The primary outcome measures included safety and tolerability.
• Furthermore, clinical outcomes were also examined.

Results

• Data showed that 35 (76%) completed 24 weeks of treatment out of a total of 46 patients (initiated on full dose: n = 28; initiated on half dose: n = 18), 35 (76%).
• Infective pulmonary exacerbation, abnormal respiration, cough, and dyspnea were reported as the most common adverse events.
• Less frequent respiratory events (56% vs 71%) of shorter median duration (4 vs 9 days) were observed in patients initiating at half dose, as compared with those initiating on full dose.
• Findings demonstrated that there occurred no dose modifications or discontinuations as a result of respiratory events in patients initiating on half dose who were then increased to the full dose over 2 weeks (vs 3 each for patients on full dose).
• Researchers found that after an initial reduction, ppFEV₁ was similar to baseline from week 4 throughout the remainder of the study (least squares mean [95% confidence interval] at week 24: -0.4 [-1.9, 1.1]; p=0.6249).
• Additionally, results also indicated that, compared with the 24 weeks prior to study, the annualized hospitalization rate was lower (rate ratio: 0.41; p=0.00026) and the duration of intravenous antibiotics was shorter (mean [standard deviation] difference: -8.52 [24.91] days; p=0.0369) through study week 24.