CF: CFTR Modulation Therapy (2018-19)

Intervention
In participants with CF and Class III mutations, what is the effect of ivacaftor on weight/growth parameters and body composition?
- Conclusion
  In participants with cystic fibrosis (CF) ≤20 years of age with at least one copy of the G551D mutation (class III), 48 weeks of 150 mg ivacaftor twice daily increased WFA and BMI-for-age z-scores by 0.35 and 0.39, respectively, compared to placebo, when mean baseline BMI z-score was -0.199 and WFA z-score was -0.292. The same dose may increase BMI-for-age z-score after 8 weeks in 6-17 year olds with other gating mutations, but evidence was limited. Effect of ivacaftor on body composition in pediatric participants was not described, nor was the role of diet.
  
  In adults with CF with at least one copy of the G551D mutation and with optimal or low mean BMI at baseline, 4-48 weeks of treatment with 150 mg ivacaftor twice daily increased weight and BMI by a mean of 2.9 kg and 0.58-1.2 kg/m², respectively. There was no statistically significant effect of CFTR modulation therapy on FFM. Effect of dietary intake on the relationship of interest was not described.
- Grade: II
  - Grade I means there is Good/Strong evidence supporting the statement;
  - Grade II is Fair;
  - Grade III is Limited/Weak;
  - Grade IV is Expert Opinion Only;
  - Grade V is Not Assignable.
  - High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
  - Moderate (B) means we are moderately confident in the effect estimate;
  - Low (C) means our confidence in the effect estimate is limited;
  - Very Low (D) means we have very little confidence in the effect estimate.
  - Ungraded means a grade is not assignable.
- Evidence Summary: In participants with CF with Class III mutations, what is the effect of Ivacaftor on weight/growth parameters and body composition?
- Search Plan and Results: CF: CFTR Modulation Therapy: Ivacaftor Alone 2019
In participants with CF and Class II or IV mutations, what is the effect of ivacaftor on weight/growth parameters and body composition?
- Conclusion
  Class II: In participants with cystic fibrosis (CF) ≤20 years of age who were homozygous for the F508del mutation (class II), 16 weeks of 150mg ivacaftor twice daily had no effect on WFA or BMI z-scores compared to placebo, though baseline nutritional status for pediatric participants could not be determined. Effect of ivacaftor on body composition in pediatric participants was not described, nor was the role of diet.
  Class IV: In adults with CF with at least one copy of the R117H mutation (class IV) and optimal mean BMI, 150mg of ivacaftor twice daily for 24 weeks had no effect on BMI compared to placebo. Effect of ivacaftor on body composition in pediatric participants was not described, nor was the role of diet.
- Grade: III
  - Grade I means there is Good/Strong evidence supporting the statement;
  - Grade II is Fair;
  - Grade III is Limited/Weak;
  - Grade IV is Expert Opinion Only;
  - Grade V is Not Assignable.
  - High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
  - Moderate (B) means we are moderately confident in the effect estimate;
  - Low (C) means our confidence in the effect estimate is limited;
  - Very Low (D) means we have very little confidence in the effect estimate.
  - Ungraded means a grade is not assignable.
- Evidence Summary: In participants with CF and Class II or IV mutations, what is the effect of ivacaftor on weight/growth parameters and body composition?
- Search Plan and Results: CF: CFTR Modulation Therapy: Ivacaftor Alone 2019
In participants with CF and Class II mutations, what is the effect of ivacaftor with lumacaftor on weight/growth parameters and body composition?
- Conclusion
  In children with cystic fibrosis (CF) homozygous for the F508del mutation and ages 6-11 years, there was no effect of lumacaftor with ivacaftor on BMI-for-age z-score after 24 weeks. Effect of treatment on body composition was not described, nor was the role of diet.
  
  In adults with CF with class II mutations, results were mixed regarding the effect of lumacaftor with ivacaftor on BMI. Eight weeks of 400mg lumacaftor with 250 mg ivacaftor twice daily had no effect on BMI in participants heterozygous for the F508del mutation who had an optimal mean BMI at baseline. However, 24 weeks of this regimen significantly increased BMI in participants homozygous for F508del, and a dose of 600 mg/day lumacaftor daily and 250 mg ivacaftor twice daily had a similar effect, though nutritional status at baseline could not be determined. Effect of treatment on body composition was not described, nor was the role of diet.
- Grade: II
  - Grade I means there is Good/Strong evidence supporting the statement;
  - Grade II is Fair;
  - Grade III is Limited/Weak;
  - Grade IV is Expert Opinion Only;
  - Grade V is Not Assignable.
  - High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
  - Moderate (B) means we are moderately confident in the effect estimate;
  - Low (C) means our confidence in the effect estimate is limited;
  - Very Low (D) means we have very little confidence in the effect estimate.
  - Ungraded means a grade is not assignable.
- Evidence Summary: In participants with CF and Class II mutations, what is the effect of ivacaftor with lumacaftor on weight/growth parameters and body composition?
- Search Plan and Results: CF: CFTR Modulation Therapy: Ivacaftor with Lumacaftor 2019
In participants with CF, what is the effect of ivacaftor with tezacaftor on weight/growth parameters and body composition?
- Conclusion
  In participants with cystic fibrosis (CF) 12-20 years of age who were homozygous for F508del mutation (class II), there was no effect of 100 mg of tezacaftor once daily with 150 mg of ivacaftor twice daily for 24 weeks, compared to placebo, on change in BMI-for-age z-score, though baseline nutritional status for pediatric participants could not be determined. Effect of treatment on body composition in pediatric participants was not described, nor was the role of diet.
- Grade: III
  - Grade I means there is Good/Strong evidence supporting the statement;
  - Grade II is Fair;
  - Grade III is Limited/Weak;
  - Grade IV is Expert Opinion Only;
  - Grade V is Not Assignable.
  - High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
  - Moderate (B) means we are moderately confident in the effect estimate;
  - Low (C) means our confidence in the effect estimate is limited;
  - Very Low (D) means we have very little confidence in the effect estimate.
  - Ungraded means a grade is not assignable.
- Evidence Summary: In participants with CF, what is the effect of ivacaftor with tezacaftor on weight/growth parameters and body composition?
- Search Plan and Results: CF: CFTR Modulation Therapy: Ivacaftor with Tezacaftor 2019