Introduction: Elexacaftor/tezacaftor/ivacaftor (ETI) has shown significant improvements in pulmonary and nutritional status in persons with cystic fibrosis (pwCF). Less is known about the extrapulmonary impact of ETI and effects on airway microbiology, lung clearance index (LCI), and fraction of exhaled nitric oxide (FeNO). Methods: This is a multicenter prospective observational trial, including 79 pwCF ≥18 years eligible for ETI. Assessments were done at the initiation of and 3 and 6 months into treatment with ETI. Outcomes included forced expiratory volume in 1 s (FEV1), LCI, FeNO, sputum or cough swab culture, body mass index (BMI), cystic fibrosis questionnaire-revised respiratory domain (CFQ-R RD), sinonasal outcome test-22 (SNOT-22), general anxiety disorder-7 (GAD-7), patient health questionnaire-9 (PHQ-9), fecal elastase-1 (FE-1), adherence to baseline therapies, exacerbation rate, and adverse events. Results: Our cohort included 79 pwCF (31 ± 11(SD) years) with a baseline ppFEV1 of 68 ± 23. Forty-two (53%) pwCF were previously treated with a CFTR modulator. In the entire study group, there were significant improvements from baseline in ppFEV1, LCI, FeNO, annualized exacerbation rate, BMI, CFQ-R RD, and SNOT-22 (p < 0.05 for all). Airway culture positivity for methicillin-susceptible Staphylococcus aureus and Pseudomonas aeruginosa also decreased during the study period. There was no significant change in FE-1, GAD-7, or PHQ-9. Adherence to dornase alfa and hypertonic saline decreased. Conclusion: ETI treatment led to significant improvements in respiratory and nutritional status, alongside a decrease in adherence to chronic supportive therapies. We did not observe any significant changes in exocrine pancreas function or in questionnaire scores for depression and anxiety.

1.
Middleton
PG
,
Mall
MA
,
Drevinek
P
,
Lands
LC
,
McKone
EF
,
Polineni
D
, et al
.
Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele
.
N Engl J Med
.
2019
;
381
(
19
):
1809
19
.
2.
Heijerman
HGM
,
McKone
EF
,
Downey
DG
,
Van Braeckel
E
,
Rowe
SM
,
Tullis
E
, et al
.
Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial
.
Lancet
.
2019
;
394
(
10212
):
1940
8
.
3.
Barry
PJ
,
Mall
MA
,
Alvarez
A
,
Colombo
C
,
de Winter-de Groot
KM
,
Fajac
I
, et al
.
Triple therapy for cystic fibrosis phe508del-gating and -residual function genotypes
.
N Engl J Med
.
2021
;
385
(
9
):
815
25
.
4.
Nichols
DP
,
Paynter
AC
,
Heltshe
SL
,
Donaldson
SH
,
Frederick
CA
,
Freedman
SD
, et al
.
Clinical effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: a clinical trial
.
Am J Respir Crit Care Med
.
2022
;
205
(
5
):
529
39
.
5.
McNally
P
,
Lester
K
,
Stone
G
,
Elnazir
B
,
Williamson
M
,
Cox
D
, et al
.
Improvement in lung clearance index and chest computed tomography scores with elexacaftor/tezacaftor/ivacaftor treatment in people with cystic fibrosis aged 12 years and older - the recover trial
.
Am J Respir Crit Care Med
.
2023
;
208
(
9
):
917
29
.
6.
Burgel
PR
,
Paillasseur
JL
,
Durieu
I
,
Reynaud-Gaubert
M
,
Hamidfar
R
,
Murris-Espin
M
, et al
.
Multisystemic effects of elexacaftor-tezacaftor-ivacaftor in adults with cystic fibrosis and advanced pulmonary disease
.
Ann Am Thorax Soc
.
2024
;
21
(
7
):
1053
64
.
7.
Stylemans
D
,
Darquenne
C
,
Schuermans
D
,
Verbanck
S
,
Vanderhelst
E
.
Peripheral lung effect of elexacaftor/tezacaftor/ivacaftor in adult cystic fibrosis
.
J Cyst Fibros
.
2022
;
21
(
1
):
160
3
.
8.
Stone
RG
,
Short
C
,
Davies
JC
,
McNally
P
.
Chronic rhinosinusitis in the era of CFTR modulator therapy
.
J Cyst Fibros
.
2023
;
S1569-1993
(
23
):
00877-9
.
9.
Ramsey
ML
,
Li
SS
,
Lara
LF
,
Gokun
Y
,
Akshintala
VS
,
Conwell
DL
, et al
.
Cystic fibrosis transmembrane conductance regulator modulators and the exocrine pancreas: a scoping review
.
J Cyst Fibros
.
2023
;
22
(
2
):
193
200
.
10.
Tewkesbury
DH
,
Scott
J
,
Barry
PJ
,
Bright-Thomas
RJ
,
Hanley
KP
,
Athwal
V
, et al
.
Effects of elexacaftor/tezacaftor/ivacaftor on liver fibrosis markers in adults with cystic fibrosis
.
J Cyst Fibros
.
2024
;
23
(
2
):
349
53
.
11.
Tummler
B
.
Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor-Ivacaftor
.
Front Pharmacol
.
2023
;
14
:
1158207
.
12.
Ramsey
B
,
Correll
CU
,
DeMaso
DR
,
McKone
E
,
Tullis
E
,
Taylor-Cousar
JL
, et al
.
Elexacaftor/tezacaftor/ivacaftor treatment and depression-related events
.
Am J Respir Crit Care Med
.
2024
;
209
(
3
):
299
306
.
13.
Bilton
D
,
Canny
G
,
Conway
S
,
Dumcius
S
,
Hjelte
L
,
Proesmans
M
, et al
.
Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF working group on outcome parameters in clinical trials
.
J Cyst Fibros
.
2011
;
10
:
S79
81
.
14.
Burgel
PR
,
Durieu
I
,
Chiron
R
,
Ramel
S
,
Danner-Boucher
I
,
Prevotat
A
, et al
.
Rapid improvement after starting elexacaftor-tezacaftor-ivacaftor in patients with cystic fibrosis and advanced pulmonary disease
.
AmJRCCM
.
2021
;
204
(
1
):
64
73
.
15.
Martin
I
,
McDonald
N
,
Wilson
D
,
Ratjen
,
F
,
Grasemann
,
H
.
Elexacaftor-tezacaftor-ivacaftor increases airway nitric oxide in children with cystic fibrosis
.
J Cyst Fibros
.
2024
:
S1569-1993
(
1
):
109
11
.
16.
Grasemann
H
,
Gonska
T
,
Avolio
J
,
Klingel
M
,
Tullis
E
,
Ratjen
F
.
Effect of ivacaftor therapy on exhaled nitric oxide in patients with cystic fibrosis
.
J Cyst Fibros
.
2015
;
14
(
6
):
727
32
.
17.
Kotha
K
,
Szczesniak
RD
,
Naren
AP
,
Fenchel
MC
,
Duan
LL
,
McPhail
GL
, et al
.
Concentration of fractional excretion of nitric oxide (FeNO): a potential airway biomarker of restored CFTR function
.
J Cyst Fibros
.
2015
;
14
(
6
):
733
40
.
18.
Vincken
S
,
Verbanck
S
,
De Wachter
E
,
Vanderhelst
E
.
Exhaled nitric oxide in stable adult cystic fibrosis patients, during exacerbation and following CFTR-modifying treatment
.
Eur Respir J
.
2019
;
53
(
5
):
1802259
.
19.
Carey
RM
,
Palmer
JN
,
Adappa
ND
,
Lee
RJ
.
Loss of CFTR function is associated with reduced bitter taste receptor-stimulated nitric oxide innate immune responses in nasal epithelial cells and macrophages
.
Front Immunol
.
2023
;
14
:
1096242
.
20.
Nissen
G
,
Ben-Meir
E
,
Kopp
M
,
Shaw
M
,
Ratjen
F
,
Grasemann
H
.
Interleukin-1 beta is a potential mediator of airway nitric oxide deficiency in cystic fibrosis
.
J Cyst Fibros
.
2022
;
21
(
4
):
623
5
.
21.
Caverly
L
.
Considerations for CF airway infection sampling and impact of CFTR modulators
.
J Cyst Fibros
.
2022
;
21
(
6
):
906
7
.
22.
Beck
MR
,
Hornick
DB
,
Pena
TA
,
Singh
SB
,
Wright
BA
.
Impact of elexacaftor/tezacaftor/ivacaftor on bacterial cultures from people with cystic fibrosis
.
Pediatr Pulmonol
.
2023
;
58
(
5
):
1569
73
.
23.
Donaldson
SH
,
Corcoran
TE
,
Pilewski
JM
,
Mogayzel
P
,
Laube
BL
,
Boitet
ER
, et al
.
Effect of Elexacaftor/tezacaftor/ivacaftor on mucus and mucociliary clearance in cystic fibrosis
.
J Cyst Fibros
.
2023
;
S1569-1993
(
23
):
00931
1
.
24.
Schaupp
L
,
Addante
A
,
Völler
M
,
Fentker
K
,
Kuppe
A
,
Bardua
M
, et al
.
Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on sputum viscoelastic properties, airway infection and inflammation in patients with cystic fibrosis
.
Eur Respir J
.
2023
;
62
(
2
):
2202153
.
25.
Nichols
DP
,
Morgan
SJ
,
Skalland
M
,
Vo
AT
,
Van Dalfsen
JM
,
Singh
SB
, et al
.
Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist
.
J Clin Invest
.
2023
;
133
(
10
):
e167957
.
26.
Schwarzenberg
SJ
,
Vu
PT
,
Skalland
M
,
Hoffman
LR
,
Pope
C
,
Gelfond
D
, et al
.
Elexacaftor/tezacaftor/ivacaftor and gastro-intestinal outcomes in cystic fibrosis: report of promise-GI
.
J Cyst Fibros
.
2023
;
22
(
2
):
282
9
.
27.
Spoletini
G
,
Gillgrass
L
,
Pollard
K
,
Shaw
N
,
Williams
E
,
Etherington
C
, et al
.
Dose adjustments of Elexacaftor/Tezacaftor/Ivacaftor in response to mental health side effects in adults with cystic fibrosis
.
J Cyst Fibros
.
2022
;
21
(
6
):
1061
5
.
28.
Ibrahim
H
,
Danish
H
,
Morrissey
D
,
Deasy
KF
,
McCarthy
M
,
Dorgan
J
, et al
.
Individualized approach to elexacaftor/tezacaftor/ivacaftor dosing in cystic fibrosis, in response to self-reported anxiety and neurocognitive adverse events: a case series
.
Front Pharmacol
.
2023
;
14
:
1156621
.
29.
Mayer-Hamblett
N
,
Ratjen
F
,
Russell
R
,
Donaldson
SH
,
Riekert
KA
,
Sawicki
GS
, et al
.
Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials
.
Lancet Respir Med
.
2023
;
11
(
4
):
329
40
.
You do not currently have access to this content.