Virant-Young D, Thomas J, Woiderski S, Powers M, Carlier J, McCarty J, Kupchick T, Larder A. Cystic Fibrosis: A Novel Pharmacologic Approach to Cystic Fibrosis Transmembrane Regulator Modulation Therapy. J Am Osteopath Assoc 2015;115(9):546–555. doi: https://doi.org/10.7556/jaoa.2015.112.
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Therapy for cystic fibrosis (CF) has progressed during the past several decades. Much of this progress is because of advances in genetic testing to precisely identify the underlying cause of CF transmembrane regulator (CFTR) dysfunction. However, with more than 1900 mutations that can produce a faulty CFTR, the management of CF can remain a challenge. Several innovative drugs recently approved by the Food and Drug Administration, termed genetic modulators, target the underlying disease by modulating the CFTR defect. This review provides physicians with an established simple classification scheme to guide their use of these drugs. The treatment challenge of 1900 CFTR mutations has been simplified into 6 physiologic classes, each paired with an available therapy to offer patients the most functional improvement. Drug therapy monitoring, adverse effects, and indications for discontinuation must also be considered.
a Approximate percentages of CFTR (cystic fibrosis transmembrane regulator) mutations do not equal 100% as many individuals have multiple mutations.
b Currently under investigation
Abbreviations: ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; Cl‒, chloride.
a Recommendations: 10 mg/kg at breakfast, 10 mg/kg at lunch, and 20 mg/kg at dinner. Duration of therapy is still under investigation15 at time of publication (Phase III trials). Patients should be monitored for reversible increases in serum creatinine if ataluren is used concomitantly with other nephrotoxic medications.
b One patient did not need treatment, and the other was treated with ciprofloxacin.
c The CF (cystic fibrosis)–related pulmonary exacerbations were not believed to be caused by ataluren administration. One patient experienced an onset of symptoms before receiving ataluren and was treated with amikacin. Another patient was removed from the study owing to a chronic infection of Mycobacterium abscessus.
a Reproduced from www.clinicaltrials.gov (accessed January 11, 2015).
Abbreviations: CF, cystic fibrosis; CFTR, CF transmembrane regulator.
a Four patients withdrew, 1 in each of the VX-809 groups,owing to adverse respiratory events.
b Overall similar occurrence of pulmonary exacerbationsbetween VX-809 and placebo-treated patients.
c Dose groups had comparable adverse effect profiles.
a Data are given as No. (%).
b Recommendations: 150 mg every 12 h with fat-containing food of continuous duration. Liver enzymes (alanine aminotransferase, aspartate aminotransferase) should be monitored before initiations every 3 mo for the first year and yearly thereafter.
c Part A: 150 mg twice daily for 16 wk (n=112).Part B: Open-label, 150 mg twice daily up to 96 weeks.
d Part A: 16-wk treatment (n=28).
b Reproduced as the reported pooled safety data from Vertex Pharmaceuticals.32
c Adverse events that occurred more frequently in patients who received the combination regimens.
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