Pharmacokinetic Evidence of Steady and Sustained Drug Release from Long-Acting Implantable Corticosteroid Matrices for Chronic Rhinosinusitis.

BACKGROUND: The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. OBJECTIVE: As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. METHODS: Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) (n = 12 patients) or LYR-210 (7500 µg) (n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. RESULTS: Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. CONCLUSION: LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.

Very-Low Energy Monopolar Reduces Post-Tonsillectomy Hemorrhage Versus Standard Energy Techniques.

OBJECTIVES/HYPOTHESIS: To compare rates of post-tonsillectomy hemorrhage (PTH) between a very-low energy transfer monopolar technique (VLET) and standard energy techniques. STUDY DESIGN: Retrospective controlled cohort study. METHODS: All tonsillectomies performed by practice physicians during the period January 1, 2010 to August 31, 2019 were identified. Three groups were created based on surgeon technique utilization: the study group (VLET) and two control groups (exclusive standard energy monopolar [Standard]; exclusive "hot" technique without exclusive monopolar use [Mixed "Hot"]). Each group's PTH occurrences requiring surgical intervention (PTHRSI) were identified and rates compared. RESULTS: During the study period 11,348 tonsillectomies were performed (4,427 Standard, 1,374 VLET, 5,547 Mixed "Hot"), and 167 (1.47%) PTHRSI events identified (14 primary (<24 hours), 153 secondary (>24 hours), 12 repeat (>1PTHRSI/patient). Compared to the Standard group secondary and total PTHRSI rates (1.47%, 1.60%), the Mixed "Hot" group experienced similar rates (1.57%, P = .54; 1.68%, P = .64), but the VLET group experienced significantly lower rates (0.15%, P = .0026, adjusted odds ratio [OR] 0.114 [0.028-0.469]; 0.22%, P = .0016, adjusted OR 0.155 [0.048-0.494]). Age was a significant risk factor for both secondary and total PTHRSI (P = .0025, P = .0024, adjusted OR 1.02/year [1.01-1.03]). No significant difference in rate of primary PTHRSI was seen collectively or in any age group. The <12VLET Group experienced 0 episodes of secondary PTHRSI and a total PTHRSI rate of 0.09% in 1060 tonsillectomies. CONCLUSIONS: Standard energy techniques had an adjusted odds ratio over 8-fold higher for secondary PTHRSI and over 6-fold higher for total PTHRSI compared to the minimized energy transfer VLET technique. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2505-2511, 2021.

Randomized controlled trial of a bioabsorbable steroid-releasing implant in the frontal sinus opening.

OBJECTIVES/HYPOTHESIS: To assess safety and efficacy of a steroid-releasing implant in improving surgical outcomes when placed in the frontal sinus opening (FSO) following endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). STUDY DESIGN: Prospective, multicenter, randomized, blinded trial using an intrapatient control design. METHODS: Eighty adult (≥ 18 years) CRS patients who underwent successful bilateral frontal sinusotomy were randomized to receive a steroid-releasing implant in one FSO, whereas the contralateral control side received no implant. All patients received standard postoperative care. Endoscopic evaluations recorded at 30-days postendoscopic sinus surgery (ESS) were graded real time by clinical investigators and by an independent, blinded sinus surgeon to assess the need for postoperative interventions in the FSO. RESULTS: Implants were successfully placed in all 80 frontal sinuses, resulting in 100% implant delivery success. At 30-days post-ESS, steroid-releasing implants provided a statistically significant (P = 0.0070) reduction in the need for postoperative interventions compared to surgery alone by an independent reviewer, representing 38% relative reduction. Clinical investigators reported statistically significant reduction in this measure at 30 days (P < 0.0001) and 90 days (P = 0.0129). Clinical investigators also reported a 55.6% reduction in the need for oral steroid interventions (P = 0.0015), 75% reduction in the need for surgical interventions (P = 0.0225), 16.7% reduction in inflammation score, 54.3% reduction in restenosis rate (P = 0.0002), and 32.2% greater diameter of FSO (P < 0.0001) on treated sides compared to control at 30 days. No implant-related adverse events were reported. CONCLUSION: This study demonstrates the efficacy of steroid-releasing implants in improving outcomes of frontal sinus surgery. LEVEL OF EVIDENCE: 1b. Laryngoscope, 126:2659-2664, 2016.