James N. Palmer, MD, FARS

Credit: PennMedicine

The ‘exhalation delivery system deliver fluticasone’ system, or EDS-FLU (Xhance), may improve exacerbations, symptoms, and intrasinus opacification among patients with chronic rhinosinusitis, according to new findings.¹

EDS-FLU represents the first available nonsurgical method of addressing the needs of chronic rhinosinusitis patients, regardless of their polyp status. It is recognized as a significant step in the field, given the lack of US Food and Drug Administration (FDA)-approved treatments for chronic rhinosinusitis without nasal polyps.²

This research was led by James N. Palmer, MD, director of the division of rhinology at Penn Medicine in Philadelphia, Pennsylvania.

“The ReOpen program evaluated EDS-FLU efficacy on symptoms, QoL, intrasinus inflammation, and acute exacerbations in patients with CRS, particularly those without nasal polyps,” Palmer and colleagues wrote. “No medication has previously been shown in replicate, controlled trials to improve symptoms, QoL, intrasinus inflammation, and acute exacerbations for this population.”

Background and Findings

The EDS-FLU system is designed to introduce innovative biomechanics with the purpose of impacting the sinonasal regions found above the inferior turbinate. This specifically addresses patients’ sinus drainage pathways which can be inaccessible for conventionally-used nasal sprays.

In order to look into the efficacy of EDS-FLU among patients with chronic rhinosinusitis, investigators used 2 randomized controlled trials. The research team conducted these trials for patients with this inflammatory condition and irrespective of the existence of nasal polyps among patients.

Both the studies were titled ReOpen1 and ReOpen2, and this research involved adults with chronic rhinosinusitis with or without polyps, occurring in 120 centers found in 13 total countries. The investigators’ criteria for inclusion covered participants in the age range of 18 or older, exhibiting symptoms of the condition for 12 weeks or more and having confirmatory CT evidence of the sinus disease based upon existing criteria.

The team’s criteria for participant exclusion was made up of elements such as having had septal perforation, recent sinonasal surgery, and specific polyp qualities. Patients were either treated with EDS-FLU or EDS-placebo at a rate of twice-per-day for a total of 24 weeks, with coprimary endpoints aiming at composite symptom scores within the initial 4 weeks and ethmoid/maxillary sinus opacification evaluated by computed tomography at the 24-week period.

Overall, the investigators ended up involving 332 subjects in the ReOpen1 study. The composite symptom score least-squares mean change for treatment of EDS-FLU using 1 or 2 sprays/nostril versus those in the EDS-placebo group was -1.58 and -1.60 compared to -0.62 (P<.001, P<.001), respectively.

In the ReOpen2 study, there were 223 subjects involved in total. The investigators reported that corresponding values were shown to be -1.54 and -1.74 compared to -0.81 (P = .011, P = .001), respectively.

The research team reported that sinus opacification in the ReOpen1 study resulted in a least-squares mean change of -5.58 and -6.20 for EDS-FLU compared to those in the EDS-placebo cohort (P = .045, P = .018). While this was true, the team noted in ReOpen2 that the values were -7.00 and -5.14 versus +1.19 (P < .001, P = .009).

EDS-FLU was found by the team to have diminished acute disease exacerbations by 56% - 66%c, as opposed to those in the EDS-placebo arm (P = .001). Comparable reductions in symptoms were witnessed among subjects implementing standard-delivery nasal steroid products just prior to entering the study (P < .001).

Lastly, the investigators found that adverse events were comparable to those linked with standard-delivery intranasal steroids.

“Together, ReOpen1 and ReOpen2 provide the first replicate, controlled trial evidence demonstrating that a medication can produce subjective (symptoms) and objective (sinus opacification) disease improvement, and reduce acute exacerbations, for all patients with CRS, with or without nasal polyps,” they wrote.

References

1. ^{Palmer J, Adappa N, Chandra R, et al. Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2). The Journal of Allergy and Clinical Immunology. January 18, 2024. https://doi.org/10.1016/j.jaip.2023.12.016. Date accessed: January 22, 2024.}
2. ^{Orlandi RR, Kingdom TT, Smith TL, et al. International consensus statement on allergy and rhinology: rhinosinusitis 2021 [published correction appears in Int Forum Allergy Rhinol. 2022 Jul;12(7):974]. Int Forum Allergy Rhinol. 2021;11(3):213-739. doi:10.1002/alr.22741.}