Kaftrio eases sinonasal symptoms in children, adolescents
Study participants see improvement one month after starting treatment
Kaftrio (elexacaftor/tezacaftor/ivacaftor), branded as Trikafta in the U.S., may help clear the nasal passages and surrounding air-filled cavities, known as sinuses, in children and adolescents with cystic fibrosis (CF), according to a real-world study from France.
In the MODUL-CF study (NCT04301856), which involved 391 children and adolescents with mild impairment of lung function, those who had blocked noses at the start experienced improvements in quality of life as soon as one month after beginning treatment with Kaftrio.
The study, “Beyond the Lung. Impact of Elexacaftor/Tezacaftor/Ivacaftor on Sinonasal Disease in Children With Cystic Fibrosis,” was published in the International Forum of Allergy & Rhinology.
In CF, buildup of thick mucus along the airways may cause sinonasal symptoms, such as a runny or stuffy nose, a sinus infection, and loss of the sense of smell. These symptoms can make it difficult to breathe through the nose, adding to existing respiratory symptoms.
“There is now an increased interest in detecting and treating sinonasal disease as early as possible to prevent lower airway disease,” the researchers wrote. The lower airways include the larynx below the vocal cords, the trachea (windpipe), the bronchi (the major air passages that branch from the trachea), and the bronchioles (the smaller air passages leading to the air sacs in the lungs).
Few studies in children
Kaftrio, marketed by Vertex Pharmaceuticals, is approved in Europe for patients aged 2 and older who have at least one copy of the F508del mutation, the most common cause of CF. In addition to improving lung function, Kaftrio may help ease sinonasal symptoms, at least in adults with CF.
“Although such observations are particularly interesting in the context of CF natural history, there are still few studies about sinonasal disease and chronic rhinosinusitis (CRS) in [school-age children] and adolescents with CF,” the researchers wrote. CRS refers to a lasting infection in the nose or sinuses.
Of the 391 patients in the study, 94 were children and 297 were adolescents. More than half (57.8%) had two copies of the F508del mutation, and 209 (53.5%) had previously received Orkambi (lumacaftor/ivacaftor), another treatment approved for CF also marketed by Vertex.
Before beginning treatment with Kaftrio, 64 patients (16.4%) reported blocked noses. For 48 of them, nasal obstruction was moderate or partial, and for three, it was severe or total. Nasal obstruction was less common in patients who had previously been treated with Orkambi than in those who had not (12.9% vs. 20.3%). Four patients (1%) reported loss of their sense of smell.
“Nasal obstruction is by far the most frequent complaint in children, followed by rhinorrhea [a runny nose], while headache, snoring, sleep disorders, and hyposmia [a decreased sense of smell] are much less frequent,” the researchers wrote.
A Sinus and Nasal Quality of Life Survey (SN-5) was fully completed by 163 participants. SN-5 measures sinus infection, nasal obstruction, symptoms of allergy, emotional distress, and activity limitations. Each is scored from 1 to 7, with the overall score being the average of these. In SN-5, a higher score indicates worse quality of life.
At the start of the study, children and adolescents with CF scored a mean of 2 points on the SN-5, similar to the average score of 1.8 points in a group of healthy children in France. Of the 163 patients, 12 (7.4%) scored above the clinically significant threshold of 3.5 points, which in previous studies was associated with increased frequency of chronic sinonasal disease and allergic rhinitis.
After one year of treatment with Kaftrio, significantly fewer patients reported a blocked nose (9.5%, down from 16.4%). The overall SN-5 score dropped significantly, to 1.8 points from 2 points. In patients with blocked noses at the start of the study, a reduction from 2.93 points to 1.86 points was observed as early as one month after beginning treatment with Kaftrio.
A smaller group of 43 patients had CT scans before and after treatment with Kaftrio to watch for changes in sinus opacification using the Lund–Mackay CT score (LMKS). Opacification can occur when the sinuses are filled in with fluid. On average, the LMKS decreased from 11.3 to 4.2 points, indicating clearance of the sinuses.
While the study lacked a control group, “the use of historical French controls provides context to interpret the data,” the investigators wrote. Overall, it showed that Kaftrio improves “sinonasal symptoms and related quality of life,” the researchers wrote. “This study supports monitoring of sinonasal disease based on CF-specific sinus-related [quality of life] measures to allow for more personalized therapy,” they concluded.
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