For patients with cystic fibrosis (CF) taking elexacaftor/tezacaftor/ivacaftor (ETI), de-escalating supportive therapy was noninferior to remaining on supportive therapy, according to study findings published in the Journal of Cystic Fibrosis.
Researchers assessed the effect of de-escalating CF supportive therapies in patients who were treated with ETI. The researchers conducted a single-center, retrospective chart review of patients with CF who initiated ETI at a children’s hospital in September 2019 through December 2020. The study’s primary objective was to evaluate the noninferiority of supportive therapies de-escalation by comparing the absolute change in percent predicted (ppFEV1) from baseline to month 1 with the absolute change from baseline to month 12 after initiation of ETI with patients as their own control. Eligible participants were diagnosed with CF, heterozygous or homozygous for the F508del mutation, and at least 6 years of age.
A de-escalation algorithm was developed at the researchers’ institution before US Food and Drug Administration approval of ETI that considered medication cost and burden and patient safety. If patients were stable, CF supportive therapies could be de-escalated quuarterly, based on the algorithm.
The analysis included 174 patients, of whom 139 de-escalated at least 1 supportive therapy. The median age at ETI initiation was 24 years, and 116 (67%) patients were homozygous for the F508del mutation.
The median percent predicted forced expiratory volume in 1 second (ppFEV1) at baseline, month 1, and month 12 was 67%, 78%, and 87%, respectively. The mean difference in absolute change in ppFEV1 from baseline to month 1 vs baseline to month 12 after initiation of ETI was 1.53% (95% CI, −0.49 to 3.55).
[S]tandard-of-care CF therapies may be able to be discontinued within the context of a de-escalation algorithm while maintaining pulmonary stability.
No statistical difference in ppFEV1 was found in the study cohort between month 1 and month 12. A clinically significant increase was observed in ppFEV1 from baseline to month 1, with a slight increase at month 3, and then ppFEV1 was stable through month 12.
The participants decreased their number of CF supportive therapies by 50%. A median of 2 supportive therapies were taken at baseline per patient and de-escalated to a median of 1 therapy during 12 months. Among the 139 patients who de-escalated supportive medications, 90 (65%) adhered to the de-escalation algorithm.
Hospital admissions were reduced after ETI initiation. A total of 176 admissions were reported from 1 year before ETI initiation. In the first year on ETI therapy, 31 admissions were recorded. Of 57 patients in a registry with 2 full years of data at the end of the study, 94 admissions occurred 1 year before ETI initiation, 11 admissions occurred in the first year on ETI, and 18 admissions were reported in the second year on ETI.
All ppFEV1 baseline subgroups had a significant change from baseline to month 1, and no significant change occurred in any of the groups when ppFEV1 was compared at month 1 to months 3, 6, 9, or 12 months on ETI.
Among several limitations, many visits were conducted with use of telehealth owing to the COVID-19 pandemic, and vitals including pulmonary function tests and weight were not collected during those visits. Also, there may have been a trend toward less reliable respiratory cultures because ETI is efficacious and leads to decreased sputum production. In addition, the de-escalation of CF supportive therapies based on the algorithm changed over time according to patients’ clinical improvement, which resulted in a time-varying exposure for the primary outcome ppFEV1.
“Lung function improved in all subgroups regardless of ppFEV1 at baseline, genotype, age, de-escalation, and adherence to de-escalation algorithm,” stated the study authors. “This suggests that standard-of-care CF therapies may be able to be discontinued within the context of a de-escalation algorithm while maintaining pulmonary stability. These results support moving towards decreased medication burden and cost as well as increased quality of life.”