Session Title: Uveitis
Session Date/Time: Saturday 19/09/2015 | 11:00-12:30
Paper Time: 11:08
First Author: : A.Brézin FRANCE
Co Author(s): : P. Kestelyn J. Van Calster G. Jaffe A. Camez J. Rosenbaum A. Heiligenhaus
PURPOSE:Corticosteroids, currently the mainstay of uveitis treatment, are associated with unwanted adverse events and are not always fully effective. Accordingly, there is a clear unmet need for steroid-sparing treatments. Multiple reports describe the use of biologics, including adalimumab (ADA), in the management of noninfectious uveitis, but there is a paucity of level 1 evidence to support efficacy of these drugs. The purpose of this study was to assess ADA efficacy and safety in patients with active, noninfectious uveitis despite the use of systemic corticosteroid therapy.
Multinational (22 countries), double-masked, phase 3 clinical trial
Patients aged ≥18 years with active, noninfectious intermediate, posterior, or panuveitis (characterized by active, inflammatory chorioretinal or retinal vascular lesions; anterior chamber [AC] cell grade ≥2+; and/or vitreous haze [VH] grade ≥2+) despite ≥2 weeks of prednisone (10–60 mg/d) were randomized 1:1 to receive placebo or ADA subcutaneously. All patients received a mandatory prednisone burst and taper schedule. ADA was administered as an 80-mg loading dose, 40 mg the next week, then 40 mg every other week for ≤80 weeks. Primary endpoint was time to treatment failure (TF) at or after Week 6 in ≥1 eye: new, active, inflammatory vascular lesions relative to baseline; worsening of BCVA by ≥15 letters; inability to achieve ≤0.5+ AC or VH grades at Week 6; 2-step increase in AC cell or VH grades after Week 6. Secondary endpoints included change in AC cell grade, VH grade, and logMAR BCVA; time to macular edema (ME); and percent change in central retinal thickness (CRT), all measured from best state achieved before Week 6 to final visit. Area under the curve (AUC ) was calculated for AC cell, VH grade, and logMAR BCVA plotted against time.
Patients receiving ADA were less likely to experience TF (HR=0.5; 95% CI, 0.36-0.70; P less than 0.001), with fewer associated TF causes. Median time to TF was 13 weeks for placebo and 24 weeks for ADA. Statistically significant differences in favor of ADA versus placebo for mean change from best state before Week 6 to the final visit were met for AC cell grade (P=0.011), VH grade (P less than 0.001), logMAR BCVA (P=0.003), and CRT (P=0.020). A statistically significant difference was not observed for time to OCT evidence of cystoid ME using the full analysis set. However, a post-hoc analysis of ME (definition based on CRT, center point thickness 260-340 μm) performed on a subset of patients without macular hole or retinal detachment revealed an ME risk reduction in the ADA group of 67% versus the placebo group (HR=0.33; 95% CI, 0.12-0.90; P=0.023). Mean AUC values were significantly higher in ADA group versus placebo group, suggesting better and more durable control of AC cell (mean difference 34.3, 95%CI, 9.2-59.3; P=0.008), VH grade (35.4, 95%CI, 11.3-59.4; P=0.004), and improvement in logMAR BCVA (26.2, 95%CI, 7.0-45.3; P=0.008). Adverse event data were consistent with the safety profile across approved indications for ADA.
In patients with active, noninfectious intermediate, posterior, or panuveitis despite the use of corticosteroids, ADA significantly lowered the risk for recurrence of uveitic activity and BCVA loss. ADA also reduced the risk of developing ME in patients without preexisting macular pathology. The safety profile was consistent with the known safety profile across approved ADA indications.