PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy

Dave P Nichols¹, Scott H Donaldson², Carla A Frederick³, Steven D Freedman⁴, Daniel Gelfond⁵, Lucas R Hoffman⁶, Andrea Kelly⁷, Michael R Narkewicz⁸, Jessica E Pittman⁹, Felix Ratjen¹⁰, Scott D Sagel¹¹, Margaret Rosenfeld¹², Sarah Jane Schwarzenberg¹³, Pradeep K Singh¹⁴, George M Solomon¹⁵, Michael S Stalvey¹⁵, Shannon Kirby¹⁶, Jill M VanDalfsen¹⁶, John P Clancy¹⁷, Steven M Rowe¹⁵

Affiliations

¹ Seattle Children's Research Institute, Department of Pediatrics, University of Washington, USA. Electronic address: david.nichols@seattlechildrens.org.
² Department of Medicine, Univ. North Carolina at Chapel Hill, USA.
³ Jacobs School of Medicine and Biomedical Sciences of the University of Buffalo, USA.
⁴ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁵ Western New York Pediatric Gastroenterology, USA.
⁶ Seattle Children's Research Institute, Department of Pediatrics and Microbiology, University of Washington, USA.
⁷ Department of Endocrinology, University of Pennsylvania, USA.
⁸ Digestive Health Institute, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.
⁹ Department of Pediatrics, Washington University School of Medicine, USA.
¹⁰ Department of Pediatrics, University of Toronto, USA.
¹¹ Seattle Children's Research Institute, Department of Pediatrics and Epidemiology, University of Washington, USA.
¹² Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.
¹³ University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA.
¹⁴ Department of Microbiology, University of Washington, USA.
¹⁵ Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁶ Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, USA.
¹⁷ Cystic Fibrosis Foundation, USA.

PMID: 33619012
PMCID: PMC8686210
DOI: 10.1016/j.jcf.2021.02.003

Review

PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy

Dave P Nichols et al. J Cyst Fibros. 2021 Mar.

. 2021 Mar;20(2):205-212.

doi: 10.1016/j.jcf.2021.02.003. Epub 2021 Feb 19.

Authors

Affiliations

¹ Seattle Children's Research Institute, Department of Pediatrics, University of Washington, USA. Electronic address: david.nichols@seattlechildrens.org.
² Department of Medicine, Univ. North Carolina at Chapel Hill, USA.
³ Jacobs School of Medicine and Biomedical Sciences of the University of Buffalo, USA.
⁴ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁵ Western New York Pediatric Gastroenterology, USA.
⁶ Seattle Children's Research Institute, Department of Pediatrics and Microbiology, University of Washington, USA.
⁷ Department of Endocrinology, University of Pennsylvania, USA.
⁸ Digestive Health Institute, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.
⁹ Department of Pediatrics, Washington University School of Medicine, USA.
¹⁰ Department of Pediatrics, University of Toronto, USA.
¹¹ Seattle Children's Research Institute, Department of Pediatrics and Epidemiology, University of Washington, USA.
¹² Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.
¹³ University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA.
¹⁴ Department of Microbiology, University of Washington, USA.
¹⁵ Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁶ Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, USA.
¹⁷ Cystic Fibrosis Foundation, USA.

PMID: 33619012
PMCID: PMC8686210
DOI: 10.1016/j.jcf.2021.02.003

Abstract

Highly effective CFTR modulator drug therapy is increasingly available to those with cystic fibrosis. Multiple observational research studies are now being conducted to better understand the impacts of this important therapeutic milestone on long-term outcomes, patient care needs, and future research priorities. PROMISE is a large, multi-disciplinary academic study focused on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population age 6 years and older. The many areas of investigation and rationale for each are discussed by organ systems, along with recognition of remaining important questions that will not be addressed by this study alone. Knowledge gained through this and multiple complementary studies around the world will help to understand important health outcomes, clinical care priorities, and research needs for a large majority of people treated with these or similarly effective medications targeting the primary cellular impairment in cystic fibrosis.

Keywords: Cftr; Clinical trial; Cystic fibrosis; Drug; Elexacaftor; Ivacaftor; Modulator; Promise; Tezacaftor.

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Conflict of interest statement

Declaration of Competing Interest The primary author declares no conflict of interest with the content of this manuscript. Any potential conflicts of interest among all authors related to funding or other financial agreements will be collected and updated during the review process.

Figures

**Figure 1.**
Organ systems being evaluated in the PROMISE study. A wide range of organ systems and disease manifestations are being studied during the multi-year observational period. This will allow us to better understand the impacts of ETI therapy in clinical use and where it may be most beneficial to focus or prioritize ongoing therapeutic and research goals in those treated with highly effective modulator drugs.

See this image and copyright information in PMC

References

1. Heijerman HGM, McKone EF, Downey DG, 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. November 23 2019;394(10212):1940–1948. doi:10.1016/S0140-6736(19)32597-8 - DOI - PMC - PubMed
1. Middleton PG, Mall MA, Drevinek P, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. November 7 2019;381(19):1809–1819. doi:10.1056/NEJMoa1908639 - DOI - PMC - PubMed
1. Van Goor F, Hadida S, Grootenhuis PD, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. November 3 2009;106(44):18825–30. doi:0904709106[pii]10.1073/pnas.0904709106 - DOI - PMC - PubMed
1. Accurso FJ, Rowe SM, Clancy JP, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. November 18 2010;363(21):1991–2003. doi:10.1056/NEJMoa0909825 - DOI - PMC - PubMed
1. Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. November 03 2011;365(18):1663–72. doi:10.1056/NEJMoa1105185 - DOI - PMC - PubMed

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PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy

Affiliations

PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy

Authors

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Abstract

Conflict of interest statement

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