Table 2.
Summary of statistically significant between-group differences (P < 0.05) in clinical efficacy
| Intervention | Efficacy endpoints* | Time point# | Estimate by group | |
|---|---|---|---|---|
| Treatment | Comparison† | |||
| Sall et al. 2000 [22] | ||||
| CsA 0.05% | CFB in corneal staining | Month 4 | NR | NR |
| Month 6 | NR | NR | ||
| Mean CFB in Schirmer’s score (anaesthetised) | Month 3 | NR | NR | |
| Decrease in artificial tear use | Month 6 | NR | NR | |
| CFB in blurred vision | Month 1 | NR | NR | |
| Month 3 | NR | NR | ||
| Month 4 | NR | NR | ||
| Month 6 | NR | NR | ||
| Stevenson et al. 2000 [21] | ||||
| CsA 0.05% | Improvement in sandy or gritty feeling | Treatment week 12 | NR | NR |
| Post-treatment week 2 | NR | NR | ||
| Post-treatment week 4 | NR | NR | ||
| Improvement in ocular dryness | Post-treatment week 4 | NR | NR | |
| Baudouin et al. 2017 [28] | ||||
| CsA CE | Mean CFB in CFS | Month 1 | − 0.8 | − 0.5 |
| Month 3 | − 0.9 | − 0.7 | ||
| Month 6 | − 1.1 | − 0.8 | ||
|
Percent of patients with ≥ 25% improvement in ocular discomfort (VAS) |
Month 6 | 50.2% | 42.0% | |
| Median HLA-DR expression CFB | Month 6 | − 21,875.6 | − 1334.2 | |
| Leonardi et al. 2016 [27] | ||||
| CsA CE | Mean adjusted CFB in CFS | Month 3 | NR | NR |
| Month 6 | − 1.76 | − 1.42 | ||
| Ocular surface inflammation (HLA-DR expression) | Month 1 | 52,306.0 | 66,825.0 | |
| Month 6 | 49,917.0 | 76,062.0 | ||
| Goldberg et al. 2019 [36] | ||||
| OTX-101 0.09% | Percentage of eyes with an increase of ≥ 10 mm from baseline in Schirmer’s test scores | Day 84 | 16.6 (95% CI 13.4, 19.7) | 9.2 (95% CI 6.8, 11.7) |
| Mean CFB in total corneal staining scores | Day 28 | − 0.8 ± 1.9 | − 0.6 ± 1.8 | |
| Day 56 | − 1.3 ± 1.9 | − 0.9 ± 2.0 | ||
| Day 84 | − 1.4 ± 2.0 | − 1.2 ± 2.2 | ||
| Percentage of eyes with clear central corneas | Day 28 | 54.1 | 47.3 | |
| Day 56 | 61.7 | 52.1 | ||
| Day 84 | 65.0 | 56.9 | ||
|
LS mean CFB In total conjunctival staining |
Day 56 | NR | NR | |
| Day 84 | NR | NR | ||
| Malhotra et al. 2019 [37] | ||||
| OTX-101 0.09% | LS mean CFB in CFS total scores | Day 28 | − 0.9 ± 0.1 | − 0.5 ± 0.1 |
| Day 56 | NR | NR | ||
| Day 84 | − 1.4 ± 0.1 | − 0.9 ± 0.1 | ||
| Sheppard et al. (2020) [39] | ||||
| OTX-101 0.09% | ITT population: Percentage of eyes with increase in Schirmer’s score ≥ 10 mm from baseline | Day 84 or at early discontinuation | 16.6 | 9.0 |
| ITT population: Percentage of eyes with increase in Schirmer’s score > 5 mm from baseline | Day 84 or at early discontinuation | 28.1% | 17.7% | |
| ITT population: Schirmer’s score | Day 84 or at early discontinuation | 14.6 ± 9.9 | 12.8 ± 9.2 | |
| Subgroup with Schirmer’s score < 10 mm: Percentage of eyes with increase in Schirmer’s score ≥ 10 mm from baseline | Day 84 or at early discontinuation | 18.7 | 10.2 | |
| Subgroup with Schirmer’s score < 10 mm: Percentage of eyes with increase in Schirmer’s score > 5 mm from baseline | Day 84 or at early discontinuation | 31.0% | 19.6% | |
| Subgroup with Schirmer’s score < 10 mm: Schirmer’s score | Day 84 or at early discontinuation | 9.9 ± 7.7 | 8.1 ± 6.6 | |
| Sheppard et al. (2021) [40] | ||||
| OTX-101 0.09% (worse eye) | Percentage of patients with Schirmer’s score increase of ≥ 10 mm from baseline | Week 12 | 20.5 | 11.3 |
| Mean CFB in Schirmer’s scores | Week 12 | 4.0 ± 7.8 | 2.2 ± 6.8 | |
| LS mean ± SE CFB in total conjunctival staining | Week 8 | − 1.5 ± 0.1 | − 0.9 ± 0.1 | |
| Week 12 | − 1.7 ± 0.1 | − 1.1 ± 0.1 | ||
| Percentage of patients with clear central corneas | Week 4 | 55.1 | 45.6 | |
| Week 12 | 64 | 55.3 | ||
| Smyth-Medina et al. (2019) [38] | ||||
| OTX-101 0.09% | Mean total conjunctival staining score in both eyes | Day 28 | NR | NR |
| Day 56 | NR | NR | ||
| Day 84 | 3.9 ± 2.3 | 4.5 ± 2.5 | ||
| Mean inferior conjunctival staining score in both eyes | Day 28 | NR | NR | |
| Day 56 | NR | NR | ||
| Day 84 | 1.1 ± 0.7 | 1.3 ± 0.7 | ||
| Mean superior conjunctival staining score in both eyes | Day 28 | NR | NR | |
| Day 56 | NR | NR | ||
| Day 84 | 0.7 ± 0.6 | 0.9 ± 0.7 | ||
| Mean lateral conjunctival staining score in both eyes | Day 56 | NR | NR | |
| Day 84 | 0.6 ± 0.7 | 0.8 ± 0.7 | ||
| Tauber et al. (2018) [35] | ||||
| OTX-101 0.09% | LS mean CFB in total conjunctival staining scores | Day 84 | NR | NR |
| Mean CFB in total CFS scores | Day 28 | NR | NR | |
| Day 84 | NR | NR | ||
| Mean CFB in Schirmer’s test scores | Day 84 | 3.5 mm | 0 mm | |
| Holland et al. (2017) [49] | ||||
| Lifitegrast | Mean CFB in eye dryness score (VAS) | Day 14 | 7.9¶ (95% CI 4.3, 11.4) | |
| Day 42 | 9.3¶ (95% CI 5.4, 13.2) | |||
| Day 84 | 7.2¶ (95% CI 3.0, 11.3) | |||
| Semba et al. (2012) [48] | ||||
| Lifitegrast | Percentage of subjects demonstrating an increase of inferior corneal staining > 1.0 point CFB | Day 84 | 0 | 16.1 |
| Percentage of subjects demonstrating improvement in OSDI visual-related score | Day 84 | 50.0% | 19.6% | |
| Inferior corneal staining score mean CFB | Day 84 | NR | NR | |
| Sheppard et al. (2014) [46] | ||||
| Lifitegrast | Mean CFB in inferior CFS score | Day 84 | NR | NR |
|
Percentage of subjects with ≥ 1.0-point reduction in inferior corneal staining score |
Day 84 | 22.2 | 13.9 | |
| Mean CFB in total CFS score | Day 84 | NR | NR | |
| Mean CFB in superior CFS score | Day 84 | NR | NR | |
| Mean CFB in nasal conjunctival staining score | Day 14 | NR | NR | |
| Day 42 | NR | NR | ||
| Day 84 | NR | NR | ||
| Mean CFB in total conjunctival staining score | Day 14 | NR | NR | |
| Day 84 | NR | NR | ||
| Proportion of subjects with ≥ 1.0-point reduction in nasal conjunctival staining | Day 84 | 24.6% | 15.6% | |
| Mean eye dryness score | Day 42 | NR | NR | |
| Day 84 | NR | NR | ||
| Mean ocular discomfort score | Day 84 | NR | NR | |
| Tauber et al. (2015) [47] | ||||
| Lifitegrast | Eye dryness (VAS) CFB | Day 84 | − 35.3 ± 28.6 | − 22.75 ± 28.4 |
Data presented as mean ± SD, unless indicated otherwise
CFB change from baseline, CFS corneal fluorescein staining, CI confidence interval, CsA 0.05% cyclosporine ophthalmic emulsion 0.05%, CsA CE 0.1% (1 mg/mL) cyclosporine A cationic emulsion, F Fisher exact test, HLA-DR human leukocyte antigen DR, ITT intent-to-treat, lifitegrast lifitegrast ophthalmic solution 5.0%, LS least squares, NR not reported, OSDI ocular surface disease index, OTX-101 cyclosporine ophthalmic solution 0.09%, SE standard error, SD standard deviation, VAS visual analogue scale
*Only endpoints with statistically significant between-group results are included in this table
†Comparison group is vehicle, unless indicated otherwise
§Nominal p value
¶Treatment effect
#Time points reported as published