CFTR Modulator Adherence High in Kids, Teens on Symdeko, Orkambi

Aisha I Abdullah PhD avatar

by Aisha I Abdullah PhD |

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CFTR modulator adherence

Children and adolescents on Symdeko (tezacaftor/ivacaftor) and Orkambi (ivacaftor/lumacaftor) for cystic fibrosis (CF) had higher treatment adherence rates compared with adults given the same CFTR modulators, a nationwide study in the U.S. found.

The study also showed that adherence — patients choosing to follow through with a prescribed treatment — among people of all ages with CF was higher for those taking Symdeko than other CFTR modulators. Such therapies target defects in the CFTR protein that is mutated in CF.

The researchers suggest that the high cost of the therapies may be affecting treatment adherence rates among people with the inheritable progressive disease.

“Even though CFTR modulators have revolutionized the treatment of CF, a major limitation of these novel treatments has been the high annual drug acquisition cost, which can potentially increase the out-of-pocket spending for patients,” the researchers wrote.

The study, “Adherence to cystic fibrosis transmembrane conductance regulator (CFTR) modulators: analysis of a national specialty pharmacy database,” was published in the Journal of Drug Assessment.

More than 350 CF-causing mutations have been identified in the CFTR gene that encodes a protein of the same name. Four CFTR modulators are currently approved by the U.S. Food and Drug Administration to treat CF: Orkambi, Symdeko, Kalydeco (ivacaftor), and Trikafta (elexacaftor/tezacaftor/ivacaftor).

While these treatments effectively address the underlying cause of CF, their high cost can make them inaccessible to some patients.

To learn more, a team of researchers in the U.S. investigated treatment adherence among CF patients — who received prescription refills for Orkambi, Symdeko, or Kalydeco — from September 2017 to August 2018 using a specialty pharmacy database.

Specialty pharmacies closely monitor patients and follow up with them on a regular basis to improve treatment benefit. The researchers here noted that this pharmacy had a special CF care program for all patients on CF-related medications.

“The program is delivered by pharmacists who provide drug utilization reviews, patient counseling, timely reminders for medication refills, and monitoring side-effects to treatments; all of which are designed to maximize adherence,” the investigators wrote.

“The study results show the important role specialty pharmacy fulfils in delivering better patient outcomes for high cost, high touch medications through coordinated patient care and disease management services,” they wrote.

The team analyzed the potential relationships between treatment adherence and age and insurance type, using a 2018 Cystic Fibrosis Foundation (CFF) registry as a reference. Overall, the specialty pharmacy patients were slightly older, included more men, and were more likely to be privately insured than a representative study population. Notably, the scientists used one formula — proportion days covered or PDC —  as the only measure of treatment adherence.

A total of 2,548 patients were included in the study. Among them, 1,289 (50.6%) were prescribed Orkambi, while 784 (30.8%) were given Kalydeco, and 475 (18.6%) received Symdeko. Most of the patients (61.4%) were on primary insurance.

The mean age of the patients was 23.05, which compared with a mean age of 22.2 in the CFF registry. Of those analyzed, 1,473 were adults (57.8%) and 1,387 males (54.4%). In the CFF registry, 51.8% of patients were male.

Treatment adherence was measured by the proportion of days covered by the medicine refill or PDC — the number of days covered divided by the number of days during the study period.

The mean PDC for all three CFTR modulators was 0.86. Symdeko had the highest overall adherence with a PDC of 0.92, while Orkambi and Kalydeco both had PDCs of 0.84.

The results showed that children and adolescents taking Symdeko (0.96) and Orkambi (0.86), but not Kalydeco, had significantly higher mean PDCs than adults taking the same medications (0.91 with Symdeko and 0.83 with Orkambi).

“Studies have shown that adherence to CF medications is higher in children/adolescents compared to adults due to parent’s strong belief that the treatments are necessary. This possibly results in increased parental monitoring and timely refilling of medications,” the researchers said.

However, the team noted that other factors appear to have a large impact on adherence.

“There is evidence to also suggest that lower adherence to CF medications may be in part due to difficulties with time management, increased regimen complexity, decreased parental supervision in adolescents, perceived doubts about the necessity of treatments, stigma and reluctance to disclose CF status, and depression in both patients and their caregivers,” the researchers wrote.

According to the team, their study was limited by its retrospective nature and by the lack of data on clinical status and healthcare resource usage associated with treatment adherence. Additionally, the research did not capture patients’ data as early as treatment initiation.

“To the best of our knowledge, this is the first study to assess the adherence of three CFTR modulators using a large nationwide specialty database,” the investigators wrote.

“Future research is necessary to measure the association between adherence thresholds and healthcare resource utilization of patients on CFTR modulators,” they added. “Additionally, with the rising costs of CFTR modulator therapies specialty pharmacy should consider implementing programs such as patient follow-up and monitoring to aid in improving adherence.”


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