Adalimumab in Patients with Active Noninfectious Uveitis

BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo

Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or discontinued after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose of study drug. MAIN OUTCOME MEASURES: Main outcome measures were long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related corticosteroids. RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry, respectively, by week 150. Mean daily dose of corticosteroids was reduced from 9.4±17.1 mg/day at week 0 (n=359) to 1.5±3.9 mg/day at week 150 (n=181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab

Evolution of choroidal thickness over time and effect of early and sustained therapy in birdshot retinochoroiditis.

PurposeTo follow choroidal thickness (ChT) over time in birdshot retinochoroiditis (BRC) using enhanced depth imaging optical coherence tomography (EDI-OCT) and study the effect of early and sustained treatment on ChT.Patients and methodsEighteen patients were included and EDI-OCT measurements of ChT were analyzed retrospectively in five groups of patients with follow-up times ranging from 1 year to ≥15 years. The OCT images were evaluated and ChT was calculated under the foveola and 1500 μm temporal, nasal, superior, and inferior to the foveola. To assess the effect of treatment, 13 patients with a disease duration ≥10 years were divided into two groups depending on their treatment status: early and sustained therapy vs insufficient, late, or no treatment. ChT was compared in these two groups along with the number of typical fundus BRC lesions.ResultsThe ChT decreased (r=-0.41, P=0.0018) over the disease duration, which ranged from &lt;1 year to ≥15 years. In patients with a disease duration ≥10 years, a significant difference in ChT was noted between adequately and undertreated patients (288.3±76.9 μm vs 161.4±39.2 μm; P=0.004). At the last follow-up, in the group with insufficient therapy 10 of 11 eyes presented typical fundus BRC lesions vs 2 of 13 eyes in the treated group (P≤0.0006, F-test).ConclusionsChoroidal thickness decreases significantly over time in BRC. If undertreated, patients show thinner choroids compared with adequately treated individuals and present significantly more BRC lesions

Ocul Immunol Inflamm

PURPOSE: To assess the efficacy of anti-TNF alpha (TNF-alpha) therapy in patients with non-infectious uveitis. METHODS: This was a monocentric observational study of 21 patients with non-infectious uveitis treated with anti-TNF-alpha. The primary endpoint was the control of ocular inflammation. The secondary endpoints included the study of macular thickness and visual acuity, changes in other treatments, and adverse effects. RESULTS: The etiologies of uveitis were Behcet disease (33.3%), birdshot (14.3%), sarcoidosis (9.5%), and idiopathic uveitis (42.9%). Ocular inflammation was controlled at 3 months for 80.9% of patients, at 6 months for 94.7%, at 12 months for 83.3%, and at >12 months for 86.7%. Central macular thickness improved from 452 microm at baseline to 307.5 microm at 12 months (p = 0.002). Visual acuity also improved from 0.51(logMAR) before treatment to 0.24 at 12 months. The mean daily dose of prednisone decreased from 19.7 mg before treatment to 5.2 mg at 12 months (p < 0.001). A total of 9.5% of patients experienced serious side-effects. CONCLUSIONS: Our study confirms the efficacy of anti-TNF for the control of short-term and long-term ocular inflammation, with high rates of complete clinical remission