ADALIMUMAB IN PATIENTS WITH ACTIVE, NON-INFECTIOUS UVEITIS REQUIRING HIGH-DOSE CORTICOSTEROIDS: THE VISUAL-1 TRIAL

Background: Corticosteroids, currently the mainstay of uveitis treatment, are associated with unwanted side effects, 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 non-infectious uveitis as steroid-sparing agents, but there is a paucity of level 1 evidence to support efficacy of these drugs. Objectives: To assess ADA efficacy and safety in patients with active, sight-threatening, non-infectious uveitis despite systemic high-dose corticosteroid therapy. Methods: This multinational, double-masked trial included patients aged ≥18 years with active, non-infectious intermediate, posterior, or panuveitis on ≥2 weeks of prednisone (10–60 mg/d). Patients with active uveitis had ≥1 of: active, inflammatory chorioretinal or retinal vascular lesion; anterior chamber (AC) cell grade ≥2+; or vitreous haze (VH) grade ≥2+. Patients were randomized 1:1 to receive placebo or ADA. The ADA group received an 80-mg baseline loading dose and 40 mg every other week for up to 80 weeks; all patients received prednisone 60 mg/d that was tapered to 0 mg by week 15. Primary endpoint was time to treatment failure (TF) in ≥1 eye. TF was defined as ≥1 of: new, active, inflammatory vascular lesions; worsening of BCVA by ≥15 letters at or after week 6; inability to achieve ≤0.5+ AC cell grade or ≤0.5+ VH grade (at week 6); or 2-step increase in AC cell grade or VH grade (after week 6). Ranked secondary endpoints included change in AC cell grade, VH grade, and BCVA from the best state achieved before week 6 to the final visit. Safety was monitored during the trial. Results: 217 patients were enrolled (female, 57%; mean age, 42.7 y; mean uveitis duration, 46 mo); 22% had intermediate, 33% had posterior, and 45% had panuveitis. Patients on ADA were less likely to have TF (hazard ratio=0.5; 95% CI, 0.36–0.70; P<0.001) and had fewer causes of TF. Median time to TF was 13 weeks for placebo and 24 weeks for ADA (Figure). Worsening of AC cell grade, VH grade, and BCVA from best state achieved were reduced with ADA compared with placebo (all P<0.05). Adverse event rates were similar in the ADA and placebo groups. Conclusions: In patients with active, non-infectious intermediate, posterior, or pan uveitis despite the use of corticosteroids, ADA significantly lowered the risk for uveitic flare or BCVA loss. The safety profile was consistent with the known safety profile across approved ADA indications. Acknowledgements: Writing assistance was provided by Jillian Gee and Katherine Groschwitz of Complete Publication Solutions, LLC (CPS), Horsham, PA and Peter Rittenhouse of Complete Healthcare Communications, Inc (CHC), Chadds Ford, PA, on behalf of AbbVie. AbbVie provided funding to CPS and CHC for medical writing assistance. AbbVie funded the study (NCT01138657), contributed to its design and the data analyses, and was involved in the drafting, review, and approval of the abstract. Disclosure of Interest: G. Jaffe, MD Consultant for: AbbVie, J. Thorne, MD, PhD Grant/research support from: National Eye Institute and Allergen, Inc., Consultant for: AbbVie, Gilead, and XOMA, D. Scales, MD Consultant for: AbbVie Steering Committee, P. Franco, MD: None declared, S. Tari, MD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, A. Camez, MD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, A. Song, MD, MPH Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, M. Kron, PhD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, T. Barisani-Asenbauer, MD, PhD Consultant for: AbbVie Advisory Board, A. Dick, MBBS, MD, FMedSci Consultant for: AbbVie Advisory Board DOI: 10.1136/annrheumdis-2015-eular.2799Citation: Annals of the Rheumatic Diseases, volume 74, supplement 2, year 2015, page 849Session: Other orphan diseases (Poster Presentations )