cystic fibrosis treat with Trikafta over mono or dual therapy
- related: cystic fibrosis
- tags: #literature
For patients with cystic fibrosis who are 6 years of age or older and have either heterozygous or homozygous F508del mutations (the most common mutation in cystic fibrosis), treatment with elexacaftor plus tezacaftor plus ivacaftor is recommended (choice A is correct). Treatment with this regimen, which largely corrects the function of the abnormal cystic fibrosis transmembrane conductance regulator protein produced by the patient, can normalize sweat chloride test results, improve lung function, produce weight gain, and improve quality of life to a greater degree than can treatment with ivacaftor monotherapy, lumacaftor plus ivacaftor, or tezacaftor plus ivacaftor, or ivacaftor monotherapy (choices B, C, and D are incorrect).
Monotherapy with ivacaftor is effective for patients with at least one G551D mutation or other even less common mutations that are highly responsive to ivacaftor. However, ivacaftor is rarely used alone, even in these patients, unless they cannot tolerate dual or triple therapy, because limited evidence suggests that combination therapies are more effective even in this population. Similarly, the combination of tezacaftor plus ivacaftor is rarely used in lieu of triple therapy except in the unusual situation when a patient has one of five rare mutations that are approved for treatment with tezacaftor plus ivacaftor but not approved for triple therapy.
Lumacaftor-ivacaftor is most useful in treating patients who are 1 to 6 years old and homozygous for the F508del mutations. Although lumacaftor-ivacaftor is approved by the US Food and Drug Administration for treatment of these patients beyond 6 years of age, triple combination therapy with elexacaftor-tezacaftor-ivacaftor is preferred after age 6 years because of fewer adverse effects, fewer drug-drug interactions, and a greater improvement in FEV1.
Importantly, because of advances in treatment and consequent patient longevity, the majority of patients with cystic fibrosis are now in the adult, rather than the pediatric, age range.1