Search

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.

BACKGROUND & AIMS: Dose-optimization strategies for biologic therapies in Crohn's disease (CD) are not well established. The SERENE CD (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Crohn's Disease) trial evaluated higher vs standard adalimumab induction dosing and clinically adjusted (CA) vs therapeutic drug monitoring (TDM) maintenance strategies in patients with moderately to severely active CD. METHODS: In this phase 3, randomized, double-blind, multicenter trial, eligible adults (Crohn's Disease Activity Index score of 220-450, endoscopic evidence of mucosal inflammation, and previous failure of standard therapies) were randomized to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3; n = 308) or standard induction regimen (adalimumab 160 mg at week 0 and 80 mg at week 2; n = 206) followed by 40 mg every other week from week 4 onward. Co-primary end points included clinical remission at week 4 and endoscopic response at week 12. At week 12, patients were re-randomized to maintenance therapy optimized by Crohn's Disease Activity Index and C-reactive protein (CA; n = 92) or serum adalimumab concentrations and/or clinical criteria (TDM; n = 92); exploratory end points were evaluated at week 56. RESULTS: Similar proportions of patients receiving higher induction regimen and standard induction regimen achieved clinical remission at week 4 (44% in both; P = .939) and endoscopic response at week 12 (43% vs 39%, respectively, P = .462). Week 56 efficacy was similar between CA and TDM. Safety profiles were comparable between dosing regimens. CONCLUSIONS: Higher induction regimen was not superior to standard induction regimen, and CA and TDM maintenance strategies were similarly efficacious. Adalimumab therapy was well tolerated, and no new safety concerns were identified. (ClinicalTrials.gov, Number: NCT02065570). ispartof: GASTROENTEROLOGY vol:162 issue:7 pages:1876-1890 ispartof: location:United States status: published

Background Non-infectious uveitis (NIU) is an immune-mediated disease with clinical symptoms such as eye pain, redness, floaters, and light sensitivity. NIU is one of the leading causes of preventable blindness. Objective This review describes current and emerging therapies for NIU. Methods PubMed searches were conducted using the terms uveitis, therapy, corticosteroids, immunomodulators, biologics, intravitreal injections, intraocular implants, and adverse events deemed relevant if they presented data relating to prevalence, diagnosis, and treatment of uveitis. Results Diagnosis and management of NIU may require collaboration among different healthcare providers, including ophthalmologists and rheumatologists. Although many patients with NIU respond to corticosteroid (CS) therapy, long-term CS use can be associated with potentially severe adverse events. Localized CS therapies have been developed to reduce adverse events; however, some intravitreal injections and intraocular implants were linked to elevated intraocular pressure and cataracts. CS-sparing therapies such as biologics have demonstrated efficacy and safety while reducing CS burden. Biologics targeting tumor necrosis factor provide CS-sparing options for patients with NIU. Additional studies are needed to address long-term efficacy and safety of biologics targeting IL-6 and inhibitors of JAK/STAT. Conclusion Biologics, JAK/STAT inhibitors, and improved localized therapies may provide additional options for patients with NIU.

PURPOSE: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis.METHODS: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF).RESULTS: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40-0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37-0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41-3.54]; VISUAL II: HR = 0.45 [0.20-1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years).CONCLUSIONS: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.

Objectives To evaluate the long-term safety and efficacy of adalimumab in patients with non-infectious intermediate, posterior, or panuveitis, by immunosuppressant (IMM) use. Methods Adult patients who completed or had a treatment failure in the VISUAL I/II trials were eligible to enter the Phase III open-label extension study, VISUAL III. Patients received adalimumab 40 mg every other week in VISUAL III, and interim follow-up data were collected through Weeks 0 to 78. Efficacy measures assessed included proportion of patients with: no active inflammatory lesions in both eyes; anterior chamber (AC) cell grade ≤0.5 +in both eyes; vitreous haze (VH) grade ≤0.5 +in both eyes; quiescence (defined as no active inflammatory lesions AND AC cell grade ≤0.5 + AND VH grade ≤0.5+); and steroid-free quiescence. Mean steroid dose and mean best corrected visual acuity (BCVA) were also assessed. Missing data were imputed using non-responder imputation for categorical endpoints, last observation carried forward for continuous variables, and as-observed for steroid dose. Efficacy was analysed by IMM (methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine) use. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cut-off date of Oct 31, 2016, with analysis by IMM use. Results Of 371 patients included in the intent-to-treat analysis, 117 (31.5%) were using IMM at VISUAL III baseline (BL) and 30 (8.1%) started IMM during VISUAL III. The proportion of patients with quiescence improved over time irrespective of IMM use; compared with Week 0, 95% confidence intervals were non-overlapping at most time points (figure 1). Numeric improvements were achieved in steroid-free quiescence, steroid dose reduction, and BCVA, with no difference by IMM use. No new safety signals were detected through 130 weeks of treatment and AE rates were generally consistent with previous VISUAL trials; some AEs, notably serious infections and malignancies, were slightly higher with concomitant IMM use. Conclusions Exploratory analyses from the VISUAL III trial demonstrated that efficacy in adalimumab-treated patients was sustained or improved through 78 weeks of treatment, irrespective of IMM use. AE rates were consistent with previous VISUAL trials, although numerically higher rates for a subset of AEs were observed in patients taking IMM. Acknowledgements AbbVie funded the study and participated in study design, data analysis, and interpretation. AbbVie funded the research and provided writing support. All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the abstract; the authors maintained control over the final content. Kevin Hudson, PhD, of 2theNth, provided medical writing support, which was funded by AbbVie Inc. Disclosure of Interest Y. Guex-Crosier Consultant for: AbbVie, Santen, and Novartis, C. S. Foster Grant/research support from: Alcon, Aldeyra, Bausch and Lomb, Clearside Biomedical, Dompe, Icon, Novartis, Santen, Xoma, Aciont, and pSivida, Consultant for: Aldeyra, Bausch and Lomb Surgical, EyeGate, Novartis, pSivida, and Xoma, Speakers bureau: Alcon and Allergan, K. Nakai: None declared, H. Goto Consultant for: AbbVie, K. Douglas Shareholder of: AbbVie, Employee of: AbbVie, S. Pathai Shareholder of: AbbVie, Employee of: AbbVie, M. Kron Shareholder of: AbbVie, Employee of: AbbVie, A. P. Song Shareholder of: AbbVie, Employee of: AbbVie, J. Van Calster Consultant for: Consultant for: advisory boards for AbbVie, Allergan, Santen, and MSD, and has served as a consultant for AbbVie, Allergan, and MSD, A. Adan Consultant for: advisory boards for AbbVie, Santen, Allergan, and Novartis

Objectives To evaluate the long-term safety and efficacy of adalimumab in patients with non-infectious intermediate, posterior, or panuveitis, across different disease etiologies. Methods Adult patients in the Phase III VISUAL I/II trials, who met treatment failure (TF) criteria or who completed the study without TF, were eligible to enter the Phase III open-label extension study, VISUAL III, wherein patients received adalimumab 40 mg every other week. In this exploratory analysis, endpoints were analysed by six uveitis etiologies: i) idiopathic/other (IO), ii) birdshot chorioretinopathy (BCR), iii) multifocal choroiditis and panuveitis (MCP), iv) Vogt-Koyanagi-Harada syndrome (VKH), v) sarcoidosis, vi) Behcet’s disease (BD). Endpoints assessed through Week 78 of treatment were proportion of patients with: no active inflammatory lesions in both eyes; anterior chamber (AC) cell grade ≤0.5 +in both eyes; vitreous haze (VH) grade ≤0.5 +in both eyes; and quiescence (defined as no active inflammatory lesions AND AC cell grade ≤0.5 + AND VH grade ≤0.5+). Mean best corrected visual acuity (BCVA) was also assessed. Missing data were reported using non-responder imputation for categorical endpoints and last observation carried forward for continuous variables. Adverse events (AEs) were collected from first adalimumab dose in VISUAL III through the interim cut-off date of Oct 31, 2016. Results Of 371 patients included in the intent-to-treat analysis, disease etiology subgroups were (n[%]): IO (155 [41.8]); BCR (51 [13.7]); MCP (14 [3.8]); VKH (72 [19.4]); Sarcoidosis (52 [14.0]); BD (27 [7.3]). The proportion of patients achieving quiescence improved over time in all uveitis etiologic subgroups: IO 28.4%/63.9% (Week 0/Week 78), BCR 43.1%/64.7%, MCP 35.7%/50.0%, VKH 37.5%/63.9%, sarcoidosis 32.7%/69.2%, and BD 44.4%/74.1%. The proportions of patients with no active inflammatory lesions, AC cell grade ≤0.5+, or VH grade ≤0.5+, showed moderate increases or decreases between Weeks 0 and 78 within specific etiology subgroups; percentage ranges across all subgroups at Weeks 0/78, were 60.8–87.5/57.1–78.8% (no active inflammatory lesions), 47.2–92.2/50.0–77.8% (AC cell grade ≤0.5+), and 42.9–72.2/57.1–77.8% (VH grade ≤0.5+), respectively. Improvement or maintenance of mean BCVA was observed over time across the etiologic subgroups. AE rates were consistent with the VISUAL I and II trials. Conclusions Adalimumab increased the percentage of patients achieving quiescence and improved or maintained visual acuity at Week 78 of the VISUAL III study, with consistent results across uveitis etiologic subgroups. No new safety signals were detected with long-term adalimumab treatment. Acknowledgements AbbVie funded the study and provided medical writing support. All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the abstract. The authors maintained control over the final content. Medical writing assistance was provided by Kevin Hudson PhD, of 2theNth, which was funded by AbbVie Inc. Disclosure of Interest P. T. Merrill Consultant for: Steering Committee for the VISUAL studies and has served as a consultant and on advisory boards for Santen, Allergan, Alimera and pSivida, A. Vitale Consultant for: AbbVie and Aciont, M. Zierhut Consultant for: Scientific advisory board for AbbVie, Gilead, and Santen, E. Fortin Consultant for: advisory boards and as a consultant for AbbVie, Alcon and Allergan, H. Goto Consultant for: advisory boards for AbbVie, M. Kron Shareholder of: AbbVie, Employee of: AbbVie, A. Song Shareholder of: AbbVie, Employee of: AbbVie, K. Douglas Shareholder of: AbbVie, Employee of: AbbVie, S. Pathai Shareholder of: AbbVie, Employee of: AbbVie

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified. ispartof: OPHTHALMOLOGY vol:125 issue:7 pages:1075-1087 ispartof: location:United States status: published

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

BackgroundNon-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids.MethodsWe did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged ≤18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10–35 mg/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01124838.FindingsBetween Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77–357) in the placebo group and 245 days (119–564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8·3 months; hazard ratio 0·57, 95% CI 0·39–0·84; p=0·004). The 40th percentile for time to treatment failure was 4·8 months in the placebo group and 10·2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group).InterpretationAdalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis.FundingAbbVie

Background Uveitis causes an estimated 10–15% of cases of blindness in western countries and there is an unmet need for effective therapies for patients (pts) with non-infectious uveitis who are at risk for long-term side effects from chronic corticosteroid use. Objectives To assess adalimumab (ADA) efficacy and safety in patients with active and inactive, non-infectious uveitis. Methods Adults with non-infectious intermediate, posterior, or panuveitis were enrolled in two global phase 3, double-masked trials, VISUAL I (pts with active uveitis despite ≥2 weeks (wks) of prednisone (PS), 10–60 mg/d) and VISUAL II (pts with inactive disease dependent on 10–35 mg/d of PS, to maintain inactivity). Pts were randomized 1:1 to receive placebo (PBO) or ADA subcutaneously (80 mg wk 0, followed by 40 mg every other wk from wk 1 up to 80 wks). In VISUAL I, all pts received a PS burst followed by taper to 0 mg by wk 15. In VISUAL II, PS taper to 0 mg was mandatory by wk 19. Integrated data (main study and Japan sub-study) from VISUAL I and VISUAL II trials are reported. The primary endpoint was time to treatment failure (TF) at or after wk 6 for VISUAL I or at or after wk 2 for VISUAL II. Nine ranked secondary endpoints were assessed and adverse events (AEs) were monitored. Results The intent-to-treat (ITT) analyses included 233 (217 main study, 16 Japan sub-study) and 258 (226 main study, 32 Japan sub-study) pts from VISUAL I and VISUAL II, respectively (VISUAL I and VISUAL II: female: 58% and 61%; mean age, 43.2 years (y) and 43.1 y; mean duration of uveitis, 46 months (mt) and 59 mt). Risk of TF was reduced by 44% (VISUAL I) and 48% (VISUAL II) in ADA-treated pts compared to PBO group (VISUAL I: HR=0.56, 95% CI, 0.40–0.76, P P 18 mt, as more than half of the pts did not achieve TF by wk 80; VISUAL II). ADA-treated pts had fewer TF criteria than PBO in both studies and treatment effects were numerically in favor of ADA for most of the secondary efficacy variables (Table). ADA and PBO AE rates were similar (VISUAL I: 1063 vs 960 events/100 pt-y, VISUAL II: 854 vs 884 events/100 pt-y) in both studies, respectively. Conclusions ADA lowered the risk of uveitic flare or visual acuity loss in pts with active and inactive disease when off PS. The safety profile was consistent with the known safety profile across the approved ADA indications. Acknowledgement AbbVie funded the studies (VISUAL I [NCT01138657] and VISUAL II [NCT01124838]). All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the abstract. The authors maintained control over the final content. Medical writing assistance was provided by Gaurav Patki, PhD of AbbVie Inc. Disclosure of Interest A. P. Brezin Consultant for: AbbVie, A. D. Dick Consultant for: AbbVie, G. J. Jaffe Consultant for: AbbVie, S. Ohno Employee of: AbbVie, Santen, K. Namba Consultant for: AbbVie, H. Goto Consultant for: AbbVie, N. Inomata Shareholder of: AbbVie, Employee of: AbbVie, A. P. Song Shareholder of: AbbVie, Employee of: AbbVie, M. Kron Shareholder of: AbbVie, Employee of: AbbVie, A. Camez Shareholder of: AbbVie, Employee of: AbbVie, S. Tari Shareholder of: AbbVie, Employee of: AbbVie, Q. D. Nguyen Consultant for: AbbVie, Santen, XOMA, Bausch & Lomb

Background There is an unmet need for effective therapies for patients (pts) with non-infectious intermediate, posterior, or panuveitis who are at risk for long-term side effects from chronic corticosteroid use. The therapeutic goal in uveitis is to achieve quiescence and adalimumab (ADA) has been shown to lower uveitic flare or vision loss in pts with active (VISUAL I) and inactive (VISUAL II) uveitis 1,2 . As 40–50% of uveitis pts have accompanying extra-ocular rheumatic associations such as Behcet9s disease, sarcoidosis, understanding ocular quiescence will not only aid ophthalmologists but also rheumatologists in the overall management of the pt 3 . Objectives To assess the control of inflammation over time in pts treated with ADA in the VISUAL I and II trials. Methods Adults with non-infectious intermediate, posterior, or panuveitis were enrolled in 2 global phase 3, double-masked trials: VISUAL I (pts with active uveitis despite ≥2 weeks [wk] of prednisone [PS] 10–60 mg/d) and VISUAL II (pts with inactive disease dependent on 10–35 mg/d of PS to maintain inactivity). Pts were randomized 1:1 to receive placebo (PBO) or ADA (80mg wk0, followed by 40mg every other wk from wk1 up to 80wks). In VISUAL I, all pts received a PS burst followed by taper to 0mg by wk15. In VISUAL II, PS taper to 0mg was mandatory by wk19. Quiescence as a pre-specified endpoint was defined as no new active inflammatory lesions and anterior chamber cell grade and vitreous haze grade ≤0.5+. Steroid free quiescence at each visit was additionally reported from wks16–52 for VISUAL I and from wk20- 52 for VISUAL II. Non-responder imputation was used for missing data. Statistical comparison between PBO and ADA was based on Chi-square test. Adverse events (AEs) were monitored. Results A greater proportion of pts in the ADA group than the PBO group achieved quiescence at each visit in both VISUAL I and VISUAL II. Statistically significance between ADA and PBO groups were observed at each visit from wks6–52 for VISUAL I, excluding wks6 and 12 and from wks8–52, excluding wks12 and 32 for VISUAL II (Fig. A,B).Similar results were observed for pts in steroid-free quiescence. Statistically significant differences between ADA and PBO groups occurred at each visit from wks20–52 for VISUAL I and from wks20–52, except wk32 for VISUAL II (Fig. C,D).Safety data from the VISUAL I and II trials have previously been reported 1,2 . Rates of AEs were similar between ADA and PBO groups. Conclusions Pts with non-infectious, intermediate, posterior, or panuveitis achieved significantly higher rates of quiescence and steroid-free quiescence with ADA treatment than PBO in the VISUAL I and II trials. The safety profile of ADA was consistent with the known safety profile across the approved ADA indications. References Nguyen et.al.Arthritis Rheumatol.2015;67(suppl10) Jaffe et.al.Ann Rheum Dis.2015;74(suppl 2):849 Hooper et.al. Curr Rheum Rev.2011,7,24–38 Acknowledgement AbbVie funded the VISUAL studies and participated in the interpretation of data, review, and approval of publication. Medical writing support was provided by Gaurav Patki, PhD, of AbbVie. Disclosure of Interest R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth, Consultant for: advisory boards for Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, BMS, Janssen (formerly Centocor), GSK, Merck, Novo-Nordisk, Novartis, Pfizer, Roche, Schering-Plough, TiGenics, UCB, and Wyeth; is Director of Rheumatology Consultancy BV, I. van der Horst-Bruinsma Grant/research support from: unrestricted research grants from Pfizer, MSD and AbbVie, Consultant for: for AbbVie, MSD, UCB, S. Tari Employee of: full-time employees of AbbVie and may hold stock and/or options., S. Florentinus Employee of: full-time employees of AbbVie and may hold stock and/or options., A. Song Employee of: full-time employees of AbbVie and may hold stock and/or options., M. Kron Employee of: full-time employees of AbbVie and may hold stock and/or options., S. Pathai Employee of: full-time employees of AbbVie and may hold stock and/or options., J. Rosenbaum Grant/research support from: Alcon Research Institute., Consultant for: AbbVie, UCB, XOMA, Santen, Novartis, Medimmune, Cavtherx, Portage, Topivert, Regeneron, Allergan, and Sanofi

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 P 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