The Simplify study examined whether people with cystic fibrosis ages 12 and older on the CFTR modulator drug Trikafta® experienced a change in their lung function when they stopped either hypertonic saline or dornase alfa (Pulmozyme®). The six-week study, funded by the Cystic Fibrosis Foundation, found that participants were able to safely stop taking one of the two common CF medications without negatively affecting their health. The findings were published today in the scientific journal The Lancet Respiratory and presented at the North American Cystic Fibrosis Conference (NACFC).
The study, led by scientists from the University of Washington, Seattle Children’s Research Institute, and University Hospitals (UH) Cleveland Medical Center and conducted through the Cystic Fibrosis Therapeutics Development Network, found that individuals with relatively good lung function who stopped taking either of the inhaled therapies while on Trikafta did not experience a reduction in lung function. Participants also did not experience increased daily respiratory symptoms or an increased need for antibiotics during the six-week study. The researchers noted that longer studies were needed to better understand any impact on risk or severity of exacerbations and other long-term health effects. They strongly advised individuals with CF speak to their physicians before stopping any medication.
“We know that people with cystic fibrosis have a significant treatment burden with many taking several medications every day,” said Nicole Hamblett, PhD, professor of Pediatrics from the University of Washington and Seattle Children’s Research Institute and co-author of the paper. “The Simplify clinical study is the first to evaluate the potential for stopping certain daily medications while on Trikafta, and we hope it will provide important information to enable discussions between people with CF and their care providers.”
Few people in the study experienced adverse events. However, some individuals with lower lung function — an FEV1 less than 70% — who stopped either therapy experienced more frequent adverse events, including coughing and increased sputum.
“The study found no indication that stopping one of the daily therapies impacted the lung function of those with an FEV1 below 70%,” stated co-author Dave Nichols, MD, associate professor of Pediatrics and CF clinician from the University of Washington. “However, greater caution may be necessary when considering changes to therapies in people whose lung function is in this lower range.”
It is important to note that the Simplify study only examined whether there were changes in lung function or other outcomes when individuals taking Trikafta stopped taking a single medication (either hypertonic saline or dornase alfa). Although some participants used both hypertonic saline and dornase alfa before starting the trial, this did not significantly influence the results of studies in which each medication was continued or discontinued. Additionally, individuals participating in the study continued their airway clearance therapy and took Trikafta as prescribed throughout the six weeks.
“Our study is one of several that will provide critical insight into how to reduce the treatment burden of those living with CF while ensuring their health is not compromised,” added Alex Gifford, MD, director of the Adult Cystic Fibrosis Program at UH Cleveland Medical Center and UH Rainbow Babies & Children’s Hospital and co-author of the paper.
People with cystic fibrosis often take several medications and supplements to help manage their disease. They tend to spend an average of 2-3 hours daily managing their care.
Several other studies assessing longer-term effects on health are underway to provide additional insight into the implications of stopping medications and therapies while on Trikafta, including HERO-2 and CF-STORM. HERO-2 is focusing on using real-world, patient-reported data to further explore questions around the use of Trikafta and other CF therapies. CF-STORM has some similarities to Simplify but examines the withdrawal of hypertonic saline or dornase alfa over a 12-month period.