Effect of cyclosporine ophthalmic solution 0.09% on conjunctival staining in patients with keratoconjunctivitis sicca

Abstract

Purpose : The severity of keratoconjunctivitis sicca (KCS) can be indicated with conjunctival staining. OTX-101 0.09% is approved in the United States to increase tear production in patients with KCS. This pooled analysis of phase 2b/3 and phase 3 studies examines the effect of OTX-101 on conjunctival staining in the worse eye.

Methods : In these randomized, double-masked studies, patients self-administered 1 drop OTX-101 or vehicle in both eyes twice daily. Conjunctival staining was performed at screening, baseline, and common study days 28, 56, and 84. Zones 1 (temporal), 3 (inferior temporal), 5 (inferior nasal) , and 6 (nasal) of the conjunctiva were scored from 0–3 points (0 = no stain, 3 = densely concentrated micropuntate stain spots). Worse eye was defined as the eye with lower Schirmer’s score at baseline, or right eye if equal. Adverse events (AE) were reported throughout both studies.

Results : For zones 1, 3, 5, and 6, the baseline mean conjunctival score (standard deviation) for OTX-101 (n = 523) vs vehicle (n = 525) was 1.0 (0.7) vs 1.1 (0.8), 1.5 (0.7) vs 1.5 (0.7), 1.6 (0.7) vs 1.6 (0.8), and 1.5 (0.8) vs 1.5 (0.7), respectively. At day 28, the least square (LS) mean percent change from baseline (standard error [SE]) for zones 3 and 5 for OTX-101 vs vehicle was −14.1 (2.1) vs −8.1 (2.1) and −13.1 (2.2) vs −5.5 (2.2), respectively; P = 0.0429 and P = 0.0144, respectively. At day 56, the LS mean percent change from baseline (SE) for zones 1, 3, and 5 for OTX-101 vs vehicle were −37.2 (3.2) vs −28.1 (3.1), −21.6 (2.3) vs −10.5 (2.3), and −23.2 (2.2) vs −11.0 (2.2), respectively; P = 0.0405, P = 0.0007, and P <0.0001, respectively. At day 84, the LS mean percent change from baseline (SE) for zones 1, 3, and 5 conjunctival scores for OTX-101 vs vehicle were −41.5 (3.3) vs −31.1 (3.2), −25.5 (2.4) vs −13.3 (2.3), and −25.0 (2.4) vs −13.5 (2.4), respectively; P = 0.0235, P = 0.0003, and P = 0.0006, respectively. Pooled safety analysis (n = 524 per arm) showed most AEs were mild; instillation site pain was most common AE (21.8% vs 4.0% for OTX-101 and vehicle, respectively).

Conclusions : OTX-101 0.09% significantly improved conjunctival surface integrity in patients with KCS, with a difference seen as early as day 28 (zones 3 and 5) and day 56 (zone 1) in 3 of the 4 individual zones. OTX-101 0.09% was well tolerated.

This is a 2020 ARVO Annual Meeting abstract.