Lesser need for painkillers seen with CFTR modulator use in data study
Need for anxiety, depression treatments also fall relative to other CF patients
Treatment with CFTR modulators lessened the need for opioids and other painkillers in people with cystic fibrosis (CF), and led to a more stable use of psychotropics among those being treated for their mental health, a real-world data study from Australia reported.
These therapies also led to increases in the use of medications specific to a woman’s health needs, particularly for birth control.
“Our findings reinforce the importance of CFTR modulator therapies and strongly suggest improved patient outcomes in multiple clinical domains,” the researchers wrote in the study, ”Medication use in people with cystic fibrosis before and after modulator therapy,” published in the journal Pulmonary Pharmacology & Therapeutics.
CFTR modulators have ‘revolutionized’ CF patient care, scientists say
CF is caused by mutations in the CFTR gene that lead to a defective CFTR protein and the production of abnormally thick and sticky mucus. Mucus accumulation is responsible for most disease symptoms, including those of the lungs and digestive system.
The introduction of CFTR modulators, addressing the disease’s underlying cause, “has revolutionised CF care,” the researchers noted, adding that an estimated 90% of patients now benefit from these treatments.
“CFTR modulators not only improve or slow decline in respiratory function and reduce hospital admissions, but ongoing research demonstrates non-pulmonary improvements such as increased body mass index (BMI) and improved cystic fibrosis related-diabetes (CFRD) control,” the scientists, all with Monash University in Melbourne, wrote.
However, people with this multiorgan disease still need to take a median of 10 different medications a day to maintain their health, a number that increases with age. Few studies have looked into how modulator use impacts other CF-related treatments, and those that do usually focus on mucolytic and antimicrobial therapies.
Researchers analyzed a random 10% of medication dispensing records in the Australian Pharmaceutical Benefits Scheme from July 2013 through June 2022, identifying all prescribed CF treatments.
Widespread modulator use began in 2014 in Australia, following the country’s regulatory approval of Kalydeco (ivacaftor) and its inclusion in a publicly subsidized drug program.
In total, 247 modulator patients, with a median age of 21 and largely male (55.1%), were identified. All had a CFTR modulator dispensed at least twice within three months, were given at least one other CF-related medication in the year before starting a modulator therapy, and had at least one other medication dispensed in the three months following modulator initiation.
Another 101 CF patients with no evident use of any CFTR modulator during the study period, matched by age and sex, were included as controls.
Consistent decline seen in opioids, other painkillers with modulator use
A total of 46,380 dispensings of medication was noted across both groups. At the index date, defined as the date of the first modulator dispensing, patients on CFTR modulators were using a mean of 4.15 different medications, and controls a mean of 3.7. The mean monthly count in the previous year was 2.61 treatments among the modulator group and 3.56 among controls.
This “increase in dispensings at index date … may indicate that those who are prescribed a modulator are requiring more medications while waiting for modulator access,” the researchers wrote.
Immediately after modulator start, the mean number of dispensings was 0.9 times higher in the modulator group than among controls, but the two groups were at similar levels after about five years. This was due to an overall medication decrease over time in patients on CFTR modulators, whereas controls showed the opposite trend, the researchers noted.
Findings were similar for the modulators Kalydeco (ivacaftor), Orkambi (ivacaftor/lumacaftor), and Symdeko (tezacaftor/ivacaftor). Trikafta (elexacaftor/tezacaftor/ivacaftor), recently added to the country’s public drug plan, lacked enough data for an analysis, the study noted.
The greatest proportion of prescriptions was seen for pancreatic enzymes (19.1%), bodywide antimicrobials (16.6%), and gastrointestinal medications (14%).
After 7.5 years, the modulator group had a consistent decline in the use of painkillers — 1.7% of prescriptions, both opioids and other analgesics — in contrast to controls, whose use remained constant.
“Previous studies have shown a reduction in CF exacerbations after modulator, providing a potential explanation for our findings of reduced analgesics dispensed after initiation of modulator therapy,” the researchers wrote. Exacerbations are periods of acute symptom worsening.
“A reduction in analgesic medications was a unique and important finding of our study, as over 70% of [people with CF] have reported experiencing pain greater than that of chronic pain the general population,” they added. “Opioids have well established harms associated with their use, therefore the results of our study may suggest modulator use could reduce this risk.”
Over the same period, psychotropic dispensing significantly increased among controls but remained stable in patients on CFTR modulators. Psychotropics can be used to treat anxiety and depression, both more frequent than usual among people with CF, the researchers noted.
In addition, dispensing of medications specific to women’s health — mostly contraceptives — rose among modulator group patients and fell among controls. No hormonal contraceptives (birth control medications) were prescribed at the same time or within three months of Orkambi being dispensed, due to concerns about lumacaftor’s effects on their efficacy.
“This first real-world analysis of Australian pharmaceutical dispensing data [people with CF] initiated on a CFTR modulator, has highlighted previously unrecognised changes in medication dispensings outside the usual focus of antimicrobial, mucolytic and insulin therapies,” the researchers wrote.
“Modulator use has been shown in other studies to improve general health and life expectancy, which could mean more [women with CF] are now considering contraceptive use as they make longer life decisions,” the researchers wrote.