Does Dry Eye Disease Severity Impact Efficacy of Varenicline Solution Nasal Spray on Sign and Symptom Treatment Outcomes?

Abstract

SIGNIFICANCE There is a clinical necessity for dry eye disease treatments that perform across a broad range of presenting patient severities. Varenicline solution nasal spray (VNS), a unique cholinergic agonist ocular surface–sparing nasal spray therapy, demonstrated significant improvement in both signs and symptoms of dry eye disease in subjects with mild, moderate, and severe symptoms as the clinical studies enrolled a more real-world patient population. PURPOSE This study evaluated efficacy outcomes for VNS in patients with mild-moderate and severe dry eye disease. METHODS An analysis of integrated data from two randomized clinical trials, ONSET-1 (NCT03636061) and ONSET-2 (NCT04036292) (vehicle control [VC], n = 294; VNS 0.03 mg, n = 308), was performed. Adults 22 years or older with dry eye disease, Ocular Surface Disease Index score of ≥23, corneal fluorescein staining score of ≥2 in ≥1 regions/≥4 all regions, and Schirmer Test Score (STS) of ≤10 mm (no restrictions on Eye Dryness Score [EDS]) were included in this study. Efficacy was evaluated using analysis of covariance among pre-specified subgroups of mild-moderate and severe baseline disease severity defined by STS (≤5 vs. >5) and EDS (<60 vs. ≥60). Consistency of effect was evaluated by interaction tests. RESULTS No treatment-subgroup interactions were observed for all end points ( P > .05). The odds of achieving a ≥10-mm improvement in STS for VNS versus VC for patients with baseline STS ≤5 and >5 were 3.4(95% confidence interval, 2.0 to 5.6) and 2.3(1.3 to 4.0) and for EDS of <60 and ≥60 were 3.4(1.9 to 6.1) and 2.5(1.5 to 4.0). Least-squares mean treatment/VC differences in change from baseline in EDS for patients with baseline STS ≤5 or >5 were −7.4(95% confidence interval, −12.5 to −2.4) and −2.8(−8.7 to 3.1); EDS of <60 and ≥60 were −2.9(−8.3 to 2.5) and −8.1(−13.6 to −2.6). CONCLUSIONS Compared with VC, VNS improved tear production and patient-reported symptoms in patients with dry eye disease, demonstrating consistency of effect regardless of initial presenting severity.

OC-01 (Varenicline Solution) Nasal Spray for the Treatment of Dry Eye Disease Signs and Symptoms in Subjects with Autoimmune Disease: Integrated Data from ONSET-1 and ONSET-2

“…This level of tear production is lower than observed in the overall integrated ONSET-1 and ONSET-2 dry eye disease vehicle control group population (4.9 mm). 20 This low level of basal tear production is likely a cause of desiccating stress on the corneal and conjunctival epithelium in these patients, increasing the amount of corneal fluorescein staining and inflammatory cell markers, similar to what has been shown in botulinum toxin induced dry eye animal models. 21 In addition, it has been shown from impression cytology that the percentage of conjunctival epithelial cells undergoing apoptosis is higher in patients with autoimmune disease and dry eye symptoms.…”

Efficacy and safety of trigeminal parasympathetic pathway stimulation for dry eye: A systematic review and meta-analysis

“…Although no direct comparisons have been made between TPP stimulation and treatments such as lifitegrast and CsA, the results of the matching-adjusted indirect comparison (MAIC) showed that the improvement in Schirmer’s test score with the OC-01 nasal spray is much higher than 5% lifitegrast [ 43 ] and 0.05% CsA,[ 44 ] even several times higher, which is very valuable. Several post hoc studies on OC-01 nasal spray have shown consistent treatment effectiveness in a wide range of dry eye patients, regardless of age, race, ethnicity, artificial tear use,[ 45 ] severity (mild, moderate, or severe),[ 46 47 ] risk factors (e.g., menopause[ 48 ] and use of systemic anticholinergics or antidepressants or anxiolytics),[ 49 ] and demonstrated efficacy in both eyes. [ 47 ] The treatment benefit results of these subgroups are consistent with the overall trial results of ONSET-1 and ONSET-2.…”

Update on pharmacotherapy for dry eye

“…Clinical trial results also suggest that varenicline incites almost immediate short-term changes in conjunctival goblet cells with increased mucin in the tear film [11]. Post-hoc analysis of data from the ONSET-1 and ONSET-2 studies shows that varenicline improved tear production in a wider range of patients, regardless of initial DED severity [12]. Another post-hoc data analysis, matching-adjusted indirect comparison, was performed to compare varenicline (ONSET-2) to lifitegrast (OPUS-1 and OPUS-2) and found varenicline to be statistically superior to lifitegrast at 4 and 6 weeks of treatment [13 ▪▪ ].…”