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.

Intranasal Corticosteroid Treatment on Recovery of Long-Term Olfactory Dysfunction Due to COVID-19.

BACKGROUND AND AIMS: Olfactory dysfunction is a recognized manifestation in patients infected with Coronavirus Disease 2019 (COVID-19). This investigation aimed to assess the effect of mometasone furoate intranasal spray on the improvement of smell dysfunction in post-COVID-19 patients. MATERIALS AND METHODS: This randomized placebo-controlled trial included 80 non-hospitalized adult patients who had persistent anosmia or severe microsmia for more than 4 weeks due to COVID-19 infection. The participants were randomly allocated to the intervention or placebo group to receive mometasone furoate nasal spray or sodium chloride intranasal spray during 4 weeks of follow-up, respectively. The patients' olfactory dysfunction was assessed in terms of visual analog scale (VAS), and smell test score according to the modified version of the University of Pennsylvania smell identification test for the Iranian population. RESULTS: A total of 70 participants completed the follow-up period and were analyzed in this study. By comparing the olfactory scores including smell test and VAS scores, no significant differences were found between case and control groups at baseline, 2, and 4 weeks intervals. However, the change of both olfactory scores at pre to post-treatment intervals and 2-4 weeks was significantly higher in the mometasone group relative to the placebo group. At post-treatment, the frequency of anosmia was 22.9% reduced in the case group compared to the control group. CONCLUSION: Overall, there was no significant difference in olfactory dysfunction between the two groups during follow-up. However, based on the significant between-group difference in terms of olfactory scores changes, it seems that the nasal corticosteroids may be a positive effect on the recovery process of patients who received more than 2 weeks. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:2209-2216, 2022.

Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority the symptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance.  OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Individuals who had symptoms for less than four weeks were included in this review. Studies compared any intervention with no treatment or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were the presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome.  MAIN RESULTS: We included one study of 100 participants, which compared an intranasal steroid spray to no intervention. Participants in both groups were also advised to undertake olfactory training for the duration of the trial. Data were identified for only two of the prespecified outcomes for this review, and no data were available for the primary outcome of serious adverse effects. Intranasal corticosteroids compared to no intervention (all using olfactory training) Presence of normal olfactory function after three weeks of treatment was self-assessed by the participants, using a visual analogue scale (range 0 to 10, higher scores = better). A score of 10 represented "completely normal smell sensation". The evidence is very uncertain about the effect of intranasal corticosteroids on self-rated recovery of sense of smell (estimated absolute effect 619 per 1000 compared to 520 per 1000, risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; very low-certainty evidence).  Change in sense of smell was not reported, but the self-rated score for sense of smell was reported at the endpoint of the study with the same visual analogue scale (after three weeks of treatment). The median scores at endpoint were 10 (interquartile range (IQR) 9 to 10) for the group receiving intranasal corticosteroids, and 10 (IQR 5 to 10) for the group receiving no intervention (1 study; 100 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a small number of additional ongoing studies in this area. As this is a living systematic review, the evidence will be updated regularly to incorporate new data from these, and other relevant studies, as they become available.  For this (first) version of the living review, we identified a single study of intranasal corticosteroids to include in this review, which provided data for only two of our prespecified outcomes. The evidence was of very low certainty, therefore we were unable to determine whether intranasal corticosteroids may have a beneficial or harmful effect.

Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial.

The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, <0.001, <0.001, <0.001, respectively). The analyses also showed significant within-group differences from baseline. Nevertheless, the changes were not significant between the two groups (P: 0.444, 0.402, 0.267, 0.329). There was no significant difference between the two groups in terms of the UPSIT results (p > 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P < 0.001). Compared to olfactory training, mometasone furoate nasal spray combination with olfactory training showed a higher improvement in severe chronic anosmia by COVID-19.

Corticosteroid nasal spray for recovery of smell sensation in COVID-19 patients: A randomized controlled trial.

OBJECTIVES: To evaluate the role of the topical corticosteroid, mometasone furoate, nasal spray in the treatment of post COVID-19 anosmia. METHODS: A prospective, randomized, controlled trial was conducted among patients with post COVID-19 anosmia. One hundred patients were randomly assigned to two groups; group I included 50 patients received mometasone furoate nasal spray in an appropriate dose of 2 puff (100 µg) once daily in each nostril for 3 weeks with olfactory training, group II included 50 patients were advised to keep on olfactory training only. The assessment of smell was done using (Visual Analog Scale from 0 to 10). All patients were initially evaluated after their recovery from COVID-19 and followed up for 3 weeks. The smell scores were recorded weekly and the duration of smell loss was recorded from the onset of anosmia till the full recovery. RESULTS: In both groups, the smell scores significantly improved by the end of the third week (P < 0.001). By comparing smell scores between both groups after 1 week, 2 weeks, and 3 weeks of treatment, there were no statistically significant differences between both groups. In group I, (62%) of patients completely recovered their sense of smell after 3 weeks of treatment, compared to (52%) of patients in group II (P = 0.31). CONCLUSION: The results suggested that using mometasone furoate nasal spray as a topical corticosteroid in the treatment of post COVID-19 anosmia offers no superiority benefits over the olfactory training, regarding smell scores, duration of anosmia, and recovery rates. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04484493.