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. 2022 Apr 11;8(2):00724-2021.
doi: 10.1183/23120541.00724-2021. eCollection 2022 Apr.

CFTR modulator use and risk of nontuberculous mycobacteria positivity in cystic fibrosis, 2011-2018

Emily E Ricotta  1 , D Rebecca Prevots  1 , Kenneth N Olivier  2
Affiliations

CFTR modulator use and risk of nontuberculous mycobacteria positivity in cystic fibrosis, 2011-2018

Emily E Ricotta et al. ERJ Open Res. .

Abstract

Background: People with cystic fibrosis are at increased risk of pulmonary nontuberculous mycobacteria (NTM) disease. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are associated with reduced lung infection with pathogens like Pseudomonas aeruginosa and Staphylococcus aureus. This association has not been studied with NTM.

Methods: Using encounter-level data from the US Cystic Fibrosis Foundation Patient Registry from 2011 to 2018, we identified individuals aged >12 years with one or more NTM-negative sputum culture and information on receipt of ivacaftor therapy. We used a Cox proportional hazards model to assess the relationship between CFTR modulator usage (any and monotherapy versus combination therapy) and NTM sputum culture positivity, controlling for sex, least severe class of CFTR mutation, receipt of chronic macrolides, age, body mass index and percentage predicted forced expiratory volume.

Results: Out of 25 987 unique individuals, 17 403 individuals met inclusion criteria. During follow-up, 42% of individuals received CFTR modulator therapy, and 23% had incident NTM. The median (interquartile range) time to event was 6.1 (4.0-7.3) years for those ever receiving CFTR modulators compared to 4.0 (1.6-6.5) years in those never receiving CFTR modulators. CFTR modulator use was associated with a significantly reduced hazard of NTM culture positivity (hazard ratio (HR) 0.88, 95% CI 0.79-0.97); there was no significant difference in the hazard between those receiving ivacaftor monotherapy versus combination therapy (combination HR 1.01, 95% CI 0.79-1.23).

Conclusions: CFTR modulator therapy is associated with a decreased risk of NTM positivity in individuals with cystic fibrosis.

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Conflict of interest statement

Conflict of interest: K.N. Olivier declares a cooperative research and development agreement with Beyond Air, Inc, outside the current work. All other authors declare no competing interests.

Figures

FIGURE 1
FIGURE 1
Flowchart depicting inclusion criteria for cystic fibrosis transmembrane conductance regulator (CFTR) modulator analysis from the Cystic Fibrosis Foundation Patient Registry (CFFPR), 2011–2018. These data included only individuals aged ≥12 years. NTM: nontuberculous mycobacteria; M. tuberculosis: Mycobacterium tuberculosis.
FIGURE 2
FIGURE 2
Kaplan–Meier plots and 95% confidence intervals evaluating the event probability of patients having incident nontuberculous mycobacteria (NTM) cultures. a) Probability of incident NTM comparing receipt of any cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy to nonreceipt of CFTR modulator therapy. b) Probability of incident NTM comparing receipt of ivacaftor monotherapy, combination therapy and no modulator therapy.
See this image and copyright information in PMC

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