A phase 3 trial of mometasone furoate sinus implants for chronic sinusitis with recurrent nasal polyps

Abstract

Background: Topical intranasal corticosteroid sprays (INCSs) are standard treatment for nasal polyps (NPs), but their efficacy is reduced by poor patient compliance and impaired access of drug to the sinus mucosa. A corticosteroid-eluting sinus implant was designed to address these limitations in patients with recurrent polyposis after sinus surgery by delivering 1350 μg of mometasone furoate (MF) directly to the ethmoid sinus mucosa over approximately 90 days.

Methods: A randomized, sham-controlled, double-blind trial was undertaken in 300 adults with refractory chronic rhinosinusitis with NPs (CRSwNP), who were candidates for repeat surgery. Eligible patients were randomized (2:1) and underwent in-office bilateral placement of 2 implants or a sham procedure. All patients used the MF INCS 200 μg once daily. Co-primary efficacy endpoints were the change from baseline in nasal obstruction/congestion score and bilateral polyp grade, as determined by an independent panel based on centralized, blinded videoendoscopy review.

Results: Patients treated with implants experienced significant reductions in both nasal obstruction/congestion score (p = 0.0074) and bilateral polyp grade (p = 0.0073) compared to controls. At day 90, implants were also associated with significant reductions in 4 of 5 prespecified secondary endpoints compared to control: proportion of patients still indicated for repeat sinus surgery (p = 0.0004), percent ethmoid sinus obstruction (p = 0.0007), nasal obstruction/congestion (p = 0.0248), and decreased sense of smell (p = 0.0470), but not facial pain/pressure (p = 0.9130). One patient experienced an implant-related serious adverse event (epistaxis).

Conclusion: Significant improvements over a range of subjective and objective endpoints, including a reduction in the need for sinus surgery by 61%, suggest that MF sinus implants may play an important role in management of recurrent NP.

Trial registration: ClinicalTrials.gov NCT02291549.

Keywords: ESS; chronic rhinosinusitis; corticosteroid use; mometasone furoate implant; polyposis; sinus surgery.

© 2018 The Authors International Forum of Allergy & Rhinology, published by ARSAAOA, LLC.

Figures

Figure 1

RESOLVE II patient disposition (CONSORT diagram). CONSORT = Consolidated Standards Of Reporting Trials.

Figure 2

Secondary endpoints. (A) Change in mean nasal obstruction/congestion score (scale 0 to 3), as determined by patients using an electronic diary over 7 days immediately preceding each visit. p = 0.0556 for change from baseline to day 14, p = 0.0074 to day 30 (co‐primary efficacy endpoint, Table 2), p = 0.0129 to day 60, and p = 0.0083 to day 90 (p = 0.0248 when adjusted for multiplicity, Table 2). (B) Change in mean bilateral polyp grade as determined by clinical investigators on a scale from 0 to 8, with higher scores indicating greater severity. p < 0.0001 for change from baseline to each time point. (C) Change in percent ethmoid sinus obstruction as determined by clinical investigators using a 100‐mm visual analogue scale. p < 0.0001 for change from baseline to each time point. All values are means with 2‐sided standard error bars calculated based on intent‐to‐treat population. Data from patients who received surgical or medical interventions were imputed using most recent values prior to initiating or receiving intervention and represent intervention‐adjusted values. MFNS = mometasone furoate nasal spray.