Table 1.
Clinical Trials of Noninfectious Uveitides and Uveitic Macular Edema
| Trial Name(Reference No.) | Year | No. of Participants | Treatment Groups | Primary Outcome | Outcome Definition | Primary Result |
|---|---|---|---|---|---|---|
| HURON (42) | 2011 | NIIPPU and vitreous haze >1+ (n = 229; 81% with intermediate uveitis) | IVDI 0.7 mg vs. IVDI 0.35 mg vs. sham injection | Grade 0 vitreous haze at week 8 | SUN/NEI vitreous haze semiquantitative scoring system | Both doses of IVDI superior to sham injection (47% vs. 36% vs. 12%; P < 0.001 for each dose vs. sham) |
| Lx211–01a (57, 58) | 2008 | Active NIIPPU and ≥2+ vitreous haze (n = 245) | Voclosporin vs. placebo | Mean change in vitreous haze | SUN/NEI vitreous haze semiquantitative scoring system | Voclosporin did not meet primary outcome vs. placebo |
| Lx211–02a (57, 58) | 2008 | Inactive NIIPPU (n = 263) | Voclosporin vs. placebo | Relapse uveitis | Increase in vitreous haze or anterior chamber cells by 2 steps or decrease in visual acuity by 0.3 log10 units | Voclosporin did not meet primary outcome vs. placebo |
| Lx211–03a (57, 58) | 2008 | Active anterior uveitis (anterior chamber cells ≥2+) (n = 121) | Voclosporin vs. placebo | Mean change in anterior chamber cells | SUN anterior chamber cells semiquantitative scoring system | Voclosporin did not meet primary outcome vs. placebo |
| SHIELD Trial (59) | 2013 | Behçet disease with ≥2 recurrences in 6 months prior to enrollment (n = 118) | Sckq2 vs. Sckq4 vs. placebo | Number of recurrences over 24 weeks | Clinician-determined recurrence | Sckq2 and Sckq4 not superior to placebo (for recurrence, OR =1.4 (95% CI: 0.6, 3.1) and 1.8 (95% CI: 0.8, 4.0), respectively) |
| INSURE Trial (59) | 2013 | Active NIIPPU (n = 31) with ≥2+ vitreous haze | Sckq2 vs. Sckq4 vs. Sck150q4 placebo | Mean change vitreous haze | SUN/NEI vitreous haze semiquantitative scoring system | Sckq2, Scq4, and Sck150q4 not superior to placebo (mean Δ vitreous haze = –1.00 vs. –1.35 vs. –0.88 vs. –1.13) |
| ENDURE Trial (59) | 2013 | Inactive NIIPPU (n = 125) | Sckq2vs. Sckq4) vs. Sck150q4 vs. placebo | Time to uveitis relapse | Clinician-determined relapse | Sckq2, Sckq4, and Sck150q4 not superior to placebo (no differences in time to relapse and mean Δ ISM score: – 2.55 vs. –2.81 vs. –2.92 vs. –2.31) |
| VISUAL I (19) | 2016 | Active NIIPPU (n = 217) | Adalimumab 40 mg every other week vs. placebo | Uveitis relapse |
At 6 weeks: anterior chamber cells or vitreous haze grades >0.5+; new chorioretinal inflammatory lesions; decrease in visual acuity by ≥15 letters on a logarithmic visual acuity chart After 6 weeks: ≥2-step increase in anterior chamber cells or vitreous haze; new inflammatory chorioretinal lesions; decrease in visual acuity by ≥15 letters |
Adalimumab superior to placebo (HR = 0.50, 95% CI: 0.36, 0.70; P < 0.001) |
| VISUAL II (20) | 2016 | Inactive NIIPPU (N = 229) | Adalimumab 40 mg q other week vs. placebo | Uveitis relapse | ≥2-step increase in anterior chamber cells or vitreous haze; new inflammatory chorioretinal lesions; decrease in visual acuity by ≥15 letters | Adalimumab superior to placebo (HR = 0.57, 95% CI: 0.39, 0.84; P = 0.004) |
| SAKURA I Trial (60) | 2016 | NIIPPU with vitreous haze >1+ (n = 347) | Intravitreal sirolimus 440 μg vs. 880 μg vs. 44 μg | Grade 0 vitreous haze at 5 months | SUN/NEI vitreous haze semiquantitative scoring system | 440 μg superior to 44 μg (22.8% vs. 10.3%; P = 0.025); 880 μg not superior to 44 μg (16.4% vs. 10.3%; P = 0.600) |
| SAKURA II Trial (61) | 2020 | NIPPU with vitreous haze >1+ (n = 593) | Intravitreal sirolimus 440 μg vs. 880 μg vs. 44 μg | Grade 0 vitreous haze at 5 months | SUN/NEI vitreous haze semiquantitative scoring system | 440 μg not superior to 44 μg (19.1% vs. 17.6%; P = 0.783); 880 μg not superior to 44 μg (13.5% vs. 17.6%; P = 0.485) |
| SYCAMORE (21) | 2017 | JIA-associated uveitis on methotrexate (n = 90) | Adalimumab vs. placebo | Uveitis relapse | ≥2-step increase in or persistent (2 consecutive visits) ≥3+ anterior chamber cells on semiquantitative anterior chamber–cells scoring scale or new occurrence or worsening of associated ocular conditions. Associated ocular conditions included 1) disc edema; 2) macular edema; 3) elevated intraocular pressure > 25 mm Hg (despite anti-glaucoma medications); 4) hypotony (intraocular pressure < 6 mm Hg); or 5) ≥15-letter loss of visual acuity on a logarithmic visual acuity chart. | Adalimumab superior to placebo (HR = 0.25, 95% CI: 0.12, 0.49; P = 0.002) |
| MUST Trial & Follow-up Study (32, 33) | 2017 | Recently (≤60 days) active NIIPPU (n = 255) | FAI 0.59 mg vs. oral corticosteroids and immunosuppression | Change in visual acuity from baseline at 7 years | Letters read on logarithmic visual acuity scale | Systemic therapy superior to FAI (mean visual acuity change +1 vs. –6 letters; P = 0.006) |
| EYEGUARD B Trial (63) | 2018 | Behçet disease uveitis with posterior segment involvement (n = 83) | Gevokizumab 60 mg subcutaneously monthly vs. placebo | Time to uveitis relapse | Either ≥2-step increase in or increase to 4+ for anterior chamber cells or vitreous haze or development of retinal infiltrates or acute retinal vasculitis or ≥ 15-letter decrease in visual acuity on a logarithmic visual acuity chart | Gevokizumab not superior to placebo (relapse at 6 months 35% vs. 35%; HR = 0.85, 95% CI: 0.41, 1.77; P = 0.66) |
| Eyepoint Fluocinolone acetonide insert trial (44, 45) | 2019 | NIIPPU (n = 129) | Intravitreal FAI 0.18 mg vs. sham injection | Uveitis relapse at 6 months | ≥2-step increase in vitreous haze or ≥ 15-letter decrease in visual acuity on logarithmic visual acuity chart or use of corticosteroids (topical or regional or systemic) and/or systemic immunosuppressive drugs | FAI superior to sham injection (28% vs. 91%; P < 0.001) |
| SATURN Trial (62) | 2019 | Active NIIPPU (N = 58) | Subcutaneous sarilumab 200 mg vs. placebo | Treatment success | ≥2-step reduction in vitreous haze or prednisone <10 mg/day | Sarilumab not superior to placebo (46.1% vs. 30%; P = 0.24) |
| FAST Trial (83) | 2019 | NIIPPU (n = 194) | Methotrexate 25 mg/week vs. mycophenolate 3 gm/day | Corticosteroid sparing success at 6 months | Inactive disease, topical prednisolone acetate 1% ≤ 2 times/day, and prednisone ≤7.5 mg/day. Inactive disease defined as ≤0.5+ anterior chamber cells and ≤ 0.5+ vitreous haze and no active chorioretinal lesions | Methotrexate noninferior to mycophenolate (OR = 1.5, 95% CI: 0.81, 2.81; P = 0.20) |
| POINT Trial (68) | 2019 | Uveitic macular edema (n = 192) | Periocular TA 40 mg vs. intravitreal TA 4 mg vs. IVDI 0.7 mg | Macular CSFT on optical coherence tomography at 8 weeks | Ratio of CSFT at 8 weeks to baseline CSFT on OCT | Periocular TA inferior to IVTA and to IVDI (CSFT reduction 23% vs. 39% (P < 0.001) vs. 46% (P < 0.001). IVDI noninferior to IVTA (ratio of reductions 0.88, 99% CI: 0.71, 1.08) |
| PEACHTREE Trial (46) | 2020 | Uveitic macular edema (n = 160) | Suprachoroidal TA 4 mg vs. sham injection | Visual improvement | ≥15-letter improvement on logarithmic visual acuity chart | Suprachoroidal TA superior to sham injection (visual improvement in 47% vs. 16%; P < 0.001) |
Abbreviations: ADVISE, Adalimumab versus Conventional Immunosuppression; CI, confidence interval; CSFT, central subfield thickness; ENDURE, Safety and Efficacy of AIN457 in Patients With Quiescent Noninfectious Uveitis; EYEGUARD B, A Randomized, Double-Masked, Placebo-Controlled Study of the Efficacy of Gevokizumab in the Treatment of Patients With Behçet's Disease Uveitis (Phase III); FAI, fluocinolone acetonide implant; FAST, First-Line Antimetabolites as Steroid-Sparing Treatment; HR, hazard ratio; HURON, Chronic Uveitis Evaluation of the Intravitreal Dexamethasone Implant; INSURE, Safety and Efficacy of AIN457 in Patients With Active Noninfectious Uveitis; ISM, immunosuppressive medication score; IVDI, intravitreal dexamethasone implant; IVTA, intravitreal triamcinolone acetonide; JIA, juvenile idiopathic arthritis; NEI, National Eye Institute; NIIPPU, noninfectious intermediate, posterior, or panuveitides; OR, odds ratio; PEACHTREE, Suprachoroidal Injection of CLS-TA in Subjects With Macular Edema Associated With Noninfectious Uveitis; POINT, Periocular Versus Intravitreal Corticosteroids for Uveitic Macular Edema; SAKURA, Sirolimus Study Assessing Double-Masked Uveitis Treatment; SATURN, Sarilumab for the Treatment of Posterior Segment Noninfectious Uveitis; Sckq2, secukinumab subcutaneously 300 mg every 2 weeks; Sckq4, secukinumab subcutaneously 300 mg every 4 weeks; Sck150q, secukinumab 150 mg every 4 weeks; SHIELD, Phase III Study in Refractory Behçet's Disease; SUN, Standardization of Uveitis Nomenclature; SYCAMORE, Randomized Controlled Trial of the Clinical Effectiveness, Safety and Cost Effectiveness of Adalimumab in Combination With Methotrexate for the Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis; TA, triamcinolone acetonide; VISUAL I, Efficacy and Safety of Adalimumab in Subjects With Active Uveitis; VISUAL II, Efficacy and Safety of Adalimumab in Subjects With Inactive Uveitis; Δ, difference.
a Voclosporin.