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Impact of Discontinuing Both Hypertonic Saline and Dornase Alfa After Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis.
Mayer-Hamblett, Nicole; Gifford, Alex H; Kloster, Margaret; Russell, Renee; Braun, Andrew T; Gibson, Ronald L; Hoppe, Jordana E; Jain, Raksha; Linnemann, Rachel W; Liou, Theodore G; Lysinger, Jerimiah; Milla, Carlos; Riekert, Kristin A; Sawicki, Gregory S; Young, Julia; Nichols, David.
Afiliação
  • Mayer-Hamblett N; University of Washington, Pediatrics, Seattle, Washington, United States.
  • Gifford AH; Seattle Children's Research Institute, Seattle, Washington, United States; nicole.hamblett@seattlechildrens.org.
  • Kloster M; University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States.
  • Russell R; University Hospitals Rainbow Babies & Children's Hospital, Cleveland, Ohio, United States.
  • Braun AT; Seattle Children's Research Institute, Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle, Washington, United States.
  • Gibson RL; Seattle Children's Research Institute, Seattle, Washington, United States.
  • Hoppe JE; University of Wisconsin-Madison School of Medicine and Public Health, Medicine, Madison, Wisconsin, United States.
  • Jain R; Seattle Children's Hospital, Pediatrics, Seattle, Washington, United States.
  • Linnemann RW; Children's Hospital Colorado, Pediatrics, Aurora, Colorado, United States.
  • Liou TG; UT Southwestern, Dallas, United States.
  • Lysinger J; Emory University, Atlanta, Georgia, United States.
  • Milla C; University of Utah School of Medicine, Internal Medicine, Salt Lake City, Utah, United States.
  • Riekert KA; Billings Clinic, Montana Cystic Fibrosis Center, Billings, Montana, United States.
  • Sawicki GS; Stanford University, Pediatrics, Palo Alto, California, United States.
  • Young J; Johns Hopkins School of Medicine, Pulmonary and Critical Care Division, Baltimore, Maryland, United States.
  • Nichols D; Children's Hospital Boston, Division of Respiratory Diseases, Boston, Massachusetts, United States.
Ann Am Thorac Soc ; 2024 Jul 23.
Article em En | MEDLINE | ID: mdl-39041864
ABSTRACT
Rationale Evaluating approaches to reduce treatment burden is a research priority among people with CF (pwCF) on highly effective modulators including elexacaftor/tezacaftor/ivacaftor (ETI). Objective To evaluate the impact of discontinuing both hypertonic saline (HS) and dornase alfa (DA) versus continuing both therapies among a subgroup of participants in the SIMPLIFY study who sequentially participated in trials evaluating the independent clinical effects of discontinuing HS and DA. Methods SIMPLIFY participants ≥12 years old on ETI and comprising a subgroup using both HS and DA at study entry were randomized to the HS or DA trial, and then randomized 11 to continue or discontinue the applicable therapy for 6 weeks. After completion of the first trial, eligible participants could enroll in the second trial beginning with a 2-week run in. Study outcomes were compared across the duration of SIMPLIFY participation between a cohort remaining on both therapies during SIMPLIFY versus a cohort that sequentially discontinued both as a result of trial randomizations. Multivariable regression models were used to estimate treatment differences, adjusted for time between trials, trial order, baseline age, sex at birth and percent predicted forced expiratory volume in one second (ppFEV1) at study entry. Results There were 43 participants who discontinued both therapies by the end of SIMPLIFY and 63 who remained on both, with overall average ppFEV1 at study entry 96.7% and average duration of follow up from beginning of the first trial to completion of the second trial 3.9 months, including time between trials. No clinically meaningful difference in the change in ppFEV1 from baseline to completion of the second trial was observed between those who discontinued versus remained on both therapies (difference 0.22% Off-On, 95% CI -1.60,2.03). Changes in LCI2.5, patient reported, and safety outcomes were also comparable. Patient reported treatment burden, as measured by a CFQ-R subscale, significantly decreased in those discontinuing both therapies. Conclusions SIMPLIFY participants who sequentially discontinued both HS and DA experienced no meaningful changes in clinical outcomes and reported decreased treatment burden as compared to those who remained on both therapies. These data continue to inform a new era of post-modulator care of pwCF.

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Ann Am Thorac Soc Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Ann Am Thorac Soc Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos