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Supplemental material, Nichols_Combined_Safety_Ms_EJO_Supplementary_Table_12Oct17 for Safety and tolerability of lifitegrast ophthalmic solution 5.0%: Pooled analysis of five randomized controlled trials in dry eye disease by Kelly K Nichols, Eric D Donnenfeld, Paul M Karpecki, John A Hovanesian, Aparna Raychaudhuri, Amir Shojaei and Steven Zhang in European Journal of Ophthalmology

This article describes a two stage composite sampling scheme for the detection of defectives in a sample. The costs under these schemes are compared with the costs under exhaustive testing for the binomial and hypergeometric models.

PurposeLifitegrast is an integrin antagonist that decreases T-cell–mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED.DesignA 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial.ParticipantsAdults aged ≥18 years with use of artificial tears within 30 days, inferior corneal staining score ≥0.5 (0–4 scale), Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, and eye dryness score ≥40 (0–100 visual analogue scale [VAS]).MethodsSubjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days.Main Outcome MeasuresCo-primary efficacy end points were change, from baseline to day 84, in eye dryness score (VAS, both eyes) and inferior corneal fluorescein staining score in the designated study eye. Secondary end points were change, from baseline to day 84, in ocular discomfort score (0–4 scale) in study eye, eye discomfort score (VAS), total corneal staining score in the study eye, and nasal conjunctival lissamine green staining score (0–4 scale) in the study eye. Treatment-emergent adverse events (TEAEs) were recorded.ResultsA total of 718 subjects were randomized: placebo, n = 360; lifitegrast, n = 358 (intent-to-treat population). Lifitegrast-treated subjects experienced greater improvement in eye dryness than placebo-treated subjects (treatment effect, 12.61; 95% confidence interval [CI], 8.51–16.70; P < 0.0001). There was no between-group difference in inferior corneal staining (treatment effect, 0.03; 95% CI, −0.10 to 0.17; P = 0.6186). There was nominally significant improvement of secondary symptom end points among lifitegrast-treated subjects: ocular discomfort (nominal P = 0.0005) and eye discomfort (nominal, P < 0.0001). There were no between-group differences on secondary signs: total corneal staining and nasal lissamine staining. More lifitegrast-treated subjects (33.7%) than placebo-treated subjects (16.4%) experienced ocular TEAEs; no ocular TEAEs were serious.ConclusionsLifitegrast met the co-primary symptom end point (eye dryness) but not the co-primary sign end point (inferior corneal staining). Secondary end point findings were consistent with this pattern. Most ocular TEAEs were mild to moderate; there were no unexpected TEAEs. Lifitegrast warrants further consideration as a treatment for DED.

PurposeLifitegrast is a lymphocyte function–associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED.DesignTwelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study.ParticipantsAdults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0–4 scale), eye dryness score (EDS) ≥40 (0–100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry.MethodsAfter a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days.Main Outcome MeasuresThe primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo.ResultsIn the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04–11.28; P = 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95% CI, 5.44–13.20; P < 0.0001) and 14 (TE, 7.85; 95% CI, 4.33–11.37; P < 0.0001). No statistically significant differences were observed in ODS between treatment groups at days 84, 42, or 14. A greater improvement was observed in lifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P = 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported.ConclusionsLifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated.