Emerging Therapies for Noninfectious Uveitis: What May Be Coming to the Clinics

Table 1

Clinical trials for emergent therapies in noninfectious uveitis.

Drug	Mechanism of action	Study name; phase	Sample size	Intervention	Results
AIN457; secukinumab; (SK)	Fully humanized antibody blocks IL-17A [6]	SHIELD; Phase III	118	(i) SK 300 mg s.c. at baseline, week 1 and week 2 (loading phase), and then every 2 weeks; (ii) SK 300 mg s.c. loading phase and then monthly; (iii) Placebo s.c. loading phase and then every 2 weeks	(i) Greater reduction in mean total postbaseline composite immunosuppressive medication (ISM) in the SK group compared with placebo (𝑃=0.047); (ii) No statically significant differences in change in BCVA between the SK group and placebo; (iii) Median decrease in vitreous haze was similar among treatment groups
		INSURE; Phase III	31	(i) SK 300 mg s.c. loading phase and then every 2 weeks; (ii) SK 300 mg s.c. loading phase and then monthly; (iii) SK 150 mg s.c. loading phase and then monthly; (iv) Placebo s.c. loading phase and then every 2 weeks	(i) No major differences in mean change in vitreous haze from baseline to week 28 in all groups; (ii) ISM score 0.0 for all SK groups, 1.83 for placebo; (iii) No loss in BCVA in all the groups; (iv) No apparent dose-response relation for the incidence of AEs (adverse events)
		ENDURE; Phase III	125	(i) SK 300 mg s.c. loading phase and then every 2 weeks; (ii) SK 300 mg s.c. loading phase and then monthly; (iii) SK 150 mg s.c. loading phase and then monthly; (iv) Placebo s.c. loading phase and then every 2 weeks	(i) No statistically significant differences between all the groups in the time of first recurrence of uveitis; (ii) Composite ISM score is similar across all the groups
DE-109 sirolimus	mTOR inhibitor [7]	SAVE; Phase I	30	(i) Intravitreal sirolimus: 325 μg at days 0, 60, and 120; (ii) Subconjunctival injection: 1320 μg at days 0, 60, and 120	(i) Did not find statistically significant differences between the two study groups at month 6; (ii) improvement of two steps or more of vitreous haze in 40% of the patients
		SAVE-2; Phase II	30	(i) Intravitreal sirolimus 440 μg at baseline and months 1, 2, 3, 4, and 5 and then prn after month 6; (ii) Intravitreal sirolimus; 880 μg at baseline and months 2 and 4 and then prn after month 6	Recruiting
		SAKURA; Phase III	500	(i) Sirolimus low dose (44 μg) intravitreal; (ii) Sirolimus medium dose (440 μg) intravitreal; (iii) Sirolimus high dose (880 μg) intravitreal	Recruiting
EGP-437 iontophoresis dexamethasone phosphate	Glucocorticoid receptor antagonist [8]	Phase I/II	40	(i) 1.6 mA-min; (ii) 4.8 mA-min; (iii) 10 mA-min; (iv) 14 mA-min	(i) By day 28, 40 patients (60%) achieved an anterior chamber cell score of zero; (ii) 1.6 mA-min was the most effective dose; (iii) Intraocular pressure and BCVA remained stable throughout the study
XOMA 052 gevokizumab	Recombinant humanized anti-IL1𝛽 antibody [9]	EYEGUARD A; Active Uveitis; Phase III		(i) Placebo drug s.c.; (ii) Group 1 gevokizumab s.c.; (iii) Group 2 gevokizumab s.c.	Recruiting
		EYEGUARD C; Controlled Uveitis; Phase III		(i) Placebo drug s.c.; (ii) Dose 1 gevokizumab s.c.; (iii) Dose 2 gevokizumab s.c.	Recruiting
Abatacept; (Orencia)	CD28 inhibitor [10]	Abatacept in the Treatment of Noninfectious Uveitis; Phase II	20	(i) Abatacept 10 mg/kg for the first 6 months; (ii) At month 6 randomization to receive either 5 mg mg/kg or 10 mg/kg	Recruiting
Tocilizumab	IgG1 recombinant humanized antihuman monoclonal antibodies that target IL-6 receptors [11, 12]	STOP Uveitis; Phase I-II	36	(i) Tocilizumab 4 mg IV, 6 monthly doses, and then prn after month 6; (ii) Tocilizumab 8 mg IV; 6 monthly doses, and then prn after month 6	Recruiting
Sarilumab		Study to Analyze Sarilumab in Noninfectious Uveitis; Phase II	57	(i) Sarilumab s.c. every 2 weeks up to 50 weeks; (ii) Placebo s.c. every 2 weeks up to 50 weeks; (iii) In both groups prednisone as single therapy or in combination with methotrexate are continued	Recruiting