Impact of highly effective CFTR modulator therapy on digital clubbing in patients with cystic fibrosis


      • Through the measurement of plaster finger casts statistically significant (p = 0.05) reversibility of digital clubbing in patients with cystic fibrosis after lung transplantation is further corroborated.
      • Measurements using the finger casts of cystic fibrosis treated with highly effective modulator therapy demonstrated statistically significant (p = 0.005) reversibility of digital clubbing in cystic fibrosis patients with corresponding, susceptible mutations.
      • The findings here suggest a previously unreported effect of HEMT. It may be anticipated that a wide variety of secondary or downstream effects, such as digital clubbing, alterations in bowel flora, or glucose metabolism, will additionally become apparent.



      The association of certain disease processes with digital clubbing is well documented. Digital clubbing is often reversible after successful treatment of the underlying pathology, for example, after lung transplantation in patients with cystic fibrosis (CF). We examined the effect of highly effective Cystic Fibrosis Transmembrane Regulator (CFTR) modulators, defined for the purposes of this study as ivacaftor or the combination of ivacaftor, tezacaftor, and elexacaftor (ETI), on digital clubbing.

      Materials and Methods

      Clubbing index was measured on plaster of Paris casts of right index fingers obtained from 15 patients with cystic fibrosis, before and after initiation of CFTR modulator therapy. Similar measurements were made on casts for 9 cystic fibrosis patients who underwent lung transplantation. Measurements were made on the most recent casts available before treatment and the first cast available at least 3 months after initiation of treatment. The Wilcoxon signed-rank text was used to detect any significant difference in the pre- and post-treatment casts for each individual.


      A significant decrease in the clubbing index was found after both lung transplantation and treatment with highly effective CFTR modulator therapy.


      These results add to the body of evidence demonstrating the efficacy of highly effective CFTR modulator therapy, the first agents that act directly at the dysfunctional chloride channel responsible for CF. By demonstrating that CFTR modulator therapy is capable of reversing digital clubbing, this study suggests a beneficial effect on lung pathology aside from air flow and gas transfer.

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