Simplifying Therapies in Cystic Fibrosis
July 07, 2022
Innovations in Pulmonology & Sleep Medicine | Summer 2022
In the genetic disease cystic fibrosis (CF), the lack of a protein called CFTR (CF transmembrane conductance regulator) causes an imbalance of salt and water. Respiratory failure from lung damage results in limited survival in this population.
However, thanks to specialized multidisciplinary care centers and therapeutic innovation, the longevity of people with CF has been increasing over the past several decades. Treatments such as airway clearance and inhaled medications, while beneficial to patients’ lungs, are time consuming and burdensome. Oral medications called modulators are now available that improve lung function and reduce symptoms by restoring function of the CFTR protein.
“Most people with CF receiving a CFTR modulator feel better, although results vary. In general, though, these medications have improved health so much that we have to question whether it’s safe to stop other treatments we previously considered indispensable,” says Alex Gifford, MD, FCCP, Director of the Adult Cystic Fibrosis Program at University Hospitals Cleveland Medical Center.
SIMPLIFY Clinical Trial
Uncertainty about the role of chronic therapies in people with CF who benefit from CFTR modulator treatment prompted the SIMPLIFY trial (Impact of Discontinuing Chronic Therapies in People with Cystic Fibrosis on Highly Effective CFTR Modulator Therapy). SIMPLIFY is sponsored by the Cystic Fibrosis Foundation and is being conducted by the Therapeutics Development Network, a consortium of academic medical centers that conducts CF clinical trials.
SIMPLIFY includes people ages 12 and older with CF being treated with the triple-combination CFTR modulator, elexacaftor-tezacaftor-ivacaftor and baseline lung function within specific ranges according to age. After a two-week period to confirm routine use of inhaled hypertonic saline or dornase alfa, investigators randomly assign participants to continue or stop each medication for six weeks, then measure change in lung function between groups who continue or stop each medication. As of May 24, 2022, SIMPLIFY had exceeded its goal of enrolling more than 800 patients.
“SIMPLIFY is innovative in that each study focuses on confirming non-inferiority of withdrawing, rather than adding, a medication to standard care,” says Dr. Gifford. “We want to make sure that within a pre-specified margin of error, there is no significant difference in lung function between groups that stopped and continued each drug. We will present results at the North American Cystic Fibrosis Conference in November.”
SIMPLIFY investigators wanted to study medications that would make the biggest impact on the lives of people with CF if they confirmed non-inferiority of withdrawal.
“We heard from patients, families and physicians that using inhaled hypertonic saline and dornase alfa required a lot of time and energy,” says Dr. Gifford. “And based on how these drugs work, it made sense to use lung function as the main outcome of the study.”
What it might mean for CF patients
If SIMPLIFY confirms there is no detrimental short-term effect of stopping hypertonic saline or dornase alfa on lung function in patients taking highly effective CFTR modulator therapy, patients and physicians could make more informed decisions.
“Even if SIMPLIFY demonstrates non-inferiority of stopping these medications, each patient and their physician should discuss that decision,” says Dr. Gifford. “During decades of CF care, we have added treatments in hopes of incrementally improving lung health, while remaining mindful of how these treatments burden our patients. Being able to safely discontinue medications in the CFTR modulator era would be revolutionary.”
For more information about CF or SIMPLIFY, contact Dr. Gifford at 216-815-0220.
Alex Gifford, MD, FCCP
Director, Adult Cystic Fibrosis Program
University Hospitals Cleveland Medical Center
Director, Cystic Fibrosis Therapeutics Development Center in the Leroy W. Matthews Cystic Fibrosis Center
UH Rainbow Babies & Children’s Hospital
Associate Professor of Medicine
Case Western Reserve University School of Medicine