Some Sinus Relief for Cystic Fibrosis Patients on Trikafta

For cystic fibrosis (CF) patients, the benefits of elexacaftor-tezacaftor-ivacaftor (ETI; Trikafta) may extend to relief from chronic rhinosinusitis, a small cohort study suggested.

After a year of treatment with ETI, chronic rhinosinusitis was improved as measured by the Lund-Mackay sinus CT scoring system (decreasing from 5.8 [IQR 5.0-7.0] to 3.3 points [IQR 2.6-4.2]) and the Sheikh-Lind scoring system (from 3.8 [IQR 3.0-5.0] to 2.2 points [IQR 2.0-2.5]), reported Shahid Sheikh, MD, of Nationwide Children's Hospital in Columbus, Ohio, and coauthors.

However, despite these improvements, "most participants still had scores for both systems that indicated severe sinus disease," the authors reported in JAMA Otolaryngology–Head & Neck Surgery.

In any case, the 64 ETI users in the prospective study had improved lung function, as the percent predicted forced expiratory volume in 1 second (ppFEV₁) rose from 67 at baseline to 86 at 12 months. Body mass index (BMI) increased 9.5% from baseline measurements. Average sweat chloride levels decreased from 93 mEq/L at baseline to 45.2 mEq/L after 1 month of ETI therapy.

Positive respiratory tract cultures for Pseudomonas aeruginosa fell from 53.1% at baseline to 22.3% at 12 months (OR 0.03, 95% CI 0.01-0.15), while cultures positive for Methicillin-resistant Staphylococcus aureus (MRSA) similarly dropped from 29.7% to 17.7% (OR 0.06, 95% CI 0.01-0.54).

Christian Merlo, MD, MPH, of Johns Hopkins Medicine in Baltimore, commented that ETI has been a "life changing" treatment for many patients, leading to improved symptoms, lung function, and overall quality of life. "Just from all fronts, it's an amazing turn of events," he said.

In 2019, ETI became the first CFTR modifier therapy approved for patients with CF who have at least one F508del mutation in the CFTR gene. The indication was most recently extended to include children ages 2 to 5 years old.

"Fifty years ago this was a fatal disease. I've never seen anything like this in medicine ... I've read about it with the discovery of insulin, or maybe with HIV therapy," Merlo said. "I have medical students that work with me, and I'm like, 'You really have to remember this time, because this doesn't happen very often.' This disease is so different now."

He told MedPage Today that, anecdotally, patients' sinus symptoms do improve with treatment.

"When they're put on these medicines, they describe 'the purge,'" he said. "They cough, cough, cough, cough, cough, and bring stuff up -- lots of drainage from the lungs and the sinuses. And that stops, then they have symptoms really, really decrease to the point where" some patients who had a chronic daily cough with sputum and phlegm no longer have a cough or any nasal drainage.

Sheikh and colleagues reported that at baseline, 71.9% of patients produced sputum for the microbial airway cultures while the other 28.2% relied on throat swabs. Following a year of ETI treatment, the proportion of people producing sputum fell to 23.4%, of whom 53.3% had sputum cultures that were positive for either MRSA, P. aeruginosa, or both bacteria.

Sheikh's group noted that there's still much to be understood about chronic rhinosinusitis in patients with CF.

"Because CF is a multiorgan disease, the effects of CFTR modulator therapies on extrapulmonary organ systems are still being evaluated," they wrote. "There is correlation between pulmonary and sinus disease in CF, as both lower airways (lungs) and upper airways (sinuses) are colonized with similar organisms. In people with CF and progressive sinonasal involvement, sinus surgery may affect pulmonary exacerbations, though the direct relationship remains unclear."

The study was conducted at a single center from October 2019 to July 2021. While 79 patients were initially enrolled, missed follow-ups led to 64 of them (60.9% women, average age 18.5 years, all white) being included in the study cohort.

Over 60% of participants were homozygous for F508del, the most common mutation that causes CF, affecting approximately 90% of CF patients based on the literature.

Among the limitations of the study are its observational, single-center design. Other limitations include inclusion of only white patients in the trial, the lack of a control group, and high MRSA levels at the start of the study. Additionally, the study was performed during the COVID-19 pandemic, when healthcare restrictions many have impacted viral exposures.

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