CF Research Update
In the early 1960s, CF Clinics were created to provide specialized care for people with CF. Some of the initial therapies are still in existence today (such as chest physio for airway clearance) and some have been proven ineffective (such as mist tents) and discontinued. But over the past 60 years, treatments have mostly been additive – meaning we rarely took away treatments, only added on more and more things for people with CF to do as part of their daily health routine. Although this helped improve survival, it also increased the burden of care for people with CF.
Now with the availability of highly effective CFTR modulator therapy (such as Trikafta), available for ~ 90% of people with CF, the medical community is looking to simplify the treatment routines and reduce the burden of care.
The first study published is appropriately called the SIMPLIFY Trial
What do we already know?
- Nebulized Dornase alfa (Pulmozyme) and Hypertonic saline are mucolytic therapies which can make sputum thinner and easier to clear for people with CF. This leads to improved lung function and reduced pulmonary exacerbations.
- Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) can restore function of the CFTR protein in certain people with CF. This makes sputum thinner and easier to clear. Trikafta has been shown to improve respiratory symptoms, lung function and reduces pulmonary exacerbations in people with CF who have certain genetic mutations.
- Inhaled therapies represent a high treatment burden for many patients with CF.
Study Question: Is it safe to stop nebulized mucolytic therapy while on Trikafta?
- This was a non-inferiority trial à “Is stopping mucolytic therapy not any worse than continuing it?”
- Participants were adolescents and adults with CF taking Trikafta.
- All participants had to be on nebulized dornase alfa, hypertonic saline (or both) prior to entering the study.
- Participants were randomly assigned to either: A) continue their nebulized mucolytic therapy, OR B) stop their mucolytic therapy. If they were on both hypertonic saline and dornase alfa, they discontinued only one of these therapies.
- Each participant’s lung function was followed for 6 weeks after changing treatment.
- The average FEV1 (lung function) for all participants at the start of the study was 96.9% predicted.
- With respect to CHANGE in FEV1 over 6 weeks: In both the dornase alfa AND hypertonic saline trials, stopping treatment was not any worse than continuing treatment.
- There was no significant decrease in lung function with stopping treatment, compared to continuing treatment over a 6 week period.
- There was a slight increase in respiratory symptoms (such as cough) in the group who discontinued their mucolytic therapy compared to those who continued.
- In people with CF on Trikafta with generally good baseline lung function, stopping nebulized hypertonic saline or dornase alfa for 6 weeks did not lead to significant decrease in lung function compared with continuing mucolytic treatment.
BUT there’s still more questions to answer!
- What happens AFTER 6 weeks…. What happens to lung function 6 months or 1 year after stopping mucolytics?
- How does stopping mucolytics affect pulmonary exacerbations?
- What about people with CF who have lower lung function or are older than the people with CF in the study?
- This trial did NOT study making changes to inhaled antibiotics (eg. Tobramycin, Aztreonam, Colistin) or airway clearance physiotherapy.
What does your Toronto CF Team recommend?
Some general comments.
The results of this study are helpful to guide decision making.
The results of the study present an average response, and every person may have a different response to stopping therapy. It is helpful to discuss this with the CF team to make the best choice for you and your lungs.
For people with CF who have good lung function (like those in the study), it may be the right choice.
It is best to only make one change in your therapy at a time so that is health or lung function change, it is not as confusing to determine the cause.
It is helpful to tell the CF team when you are changing therapy so we can document the change in your medical records.
We encourage all people with CF who are on CFTR modulator therapy to have a discussion with the CF team about simplifying your therapy.
Mayer-Hamblett N, Ratjen F, Russell R, 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. 2022;2600(22):2-4. doi:10.1016/s2213-2600(22)00434-9