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Purpose : To assess efficacy of adalimumab versus placebo in patients with active or inactive noninfectious intermediate, posterior, or panuveitis across different etiologies. Methods : VISUAL I (V-I) and VISUAL II (V-II) clinical trials included adults with active or inactive uveitis, respectively, randomized to receive adalimumab or placebo. In a post hoc subgroup analysis, time to treatment failure (TTF) starting at week 6 (V-I) or week 2 (V-II) was analyzed using the Kaplan-Meier method. Hazard ratios (HR) for TTF with 95% CI were calculated with Cox proportional hazards regression. Results : The analysis included 217 V-I patients and 226 V-II patients. Treatment failure occurred later and risk was significantly lower in patients with idiopathic uveitis receiving adalimumab versus those receiving placebo in V-I (HR = 0.50 [CI, 0.30-0.84]; P = .006) and V-II (HR = 0.43 [CI, 0.22-0.83]; P = .010). Conclusions : Treatment failure risk was lower in patients with idiopathic noninfectious uveitis receiving adalimumab versus those receiving placebo.

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 who discontinued the study 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., Main Outcome Measures: 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 systemic corticosteroids., Results: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing 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. Mean daily dose of systemic 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 were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively., Conclusions: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Non-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., Methods: We 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., Findings: Between 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)., Interpretation: Adalimumab 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., Funding: AbbVie., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

Objective: Adalimumab (ADA) was evaluated for its efficacy in patients with moderate to severely active psoriatic arthritis (PsA) and for the presence of correlations in disease change variables., Methods: Patients with inadequate response to standard PsA therapy were given 40 mg of ADA every other week for up to 12 weeks or 20 weeks. Outcome variables encompassed tender joint count (TJC), swollen joint count (SJC), physician's global assessment (PGA) of psoriasis, Health Assessment Questionnaire (HAQ), patient's global assessment (PtGA) of disease activity and pain, C-reactive protein, as well as composite measures of disease activity. Patients with inactive skin disease symptoms at baseline were excluded from the remission analyses., Results: Of 268 patients with active baseline joint and skin disease and data available at Week 12 following open-label ADA therapy, 73 achieved joint remission (27.2%, TJC ≤ 1 + SJC ≤ 1) and 144 achieved skin remission criteria (53.7%, PGA = clear/almost clear). Simultaneous joint and skin remission criteria were achieved in 16.0% and 24.8% of patients at weeks 12 and 20, respectively. In patients who did not achieve skin and/or joint remission, 12-week ADA treatment improved mean clinical and functional scores. Joint remission was more frequently associated with achieving clinically relevant outcomes including HAQ, PtGA disease activity, and PtGA pain compared to skin remission. No correlation between improvement in skin and joint disease was observed., Conclusion: ADA was effective in achieving strict criteria for remission in joint or skin disease in many patients with active PsA within 12 weeks and sustained through 20 weeks. (NCT00235885).

Background Patients with moderately-to-severely active ulcerative colitis ( UC) are unlikely to continue anti- TNF therapy in the absence of early therapeutic response. Aim To assess week 52 efficacy, safety and benefit/risk balance of adalimumab treatment in patients with moderately-to-severely active UC failing conventional therapy who achieved clinical response at week 8 in the 52-week ULTRA 2 trial. Methods Patients randomised to adalimumab (160/80 mg, week 0/2; 40 mg, every other week thereafter) in ULTRA 2 who achieved clinical response at week 8 per partial Mayo score (Mayo score without endoscopy subscore) were assessed for week 52 clinical remission, clinical response, mucosal healing, steroid-free remission and steroid discontinuation rates, overall and by prior anti- TNF use. Benefit/risk balance for the overall ITT population (regardless of week 8 responder status) was assessed using 'net efficacy adjusted for risk' ( NEAR) odds ratios. Safety was assessed using adverse event rates. Results Of 248 adalimumab-treated patients, 123 (49.6%) achieved clinical response at week 8. Of these, 30.9%, 49.6%, and 43.1% achieved clinical remission, clinical response, and mucosal healing, respectively, at week 52. Of the week 8 responders using corticosteroids at baseline ( N = 90), 21.1% achieved steroid-free remission and 37.8% were steroid-free at week 52. NEAR odds ratios indicated a positive benefit/risk balance for achievement of week 8 and week 52 response or remission without serious adverse events or serious infections. No safety concerns were identified. Conclusions Adalimumab treatment was associated with a positive benefit/risk balance in the overall population of patients with moderately-to-severely active ulcerative colitis in ULTRA 2; early response was predictive of a positive outcome at 1 year (NCT00408629). [ABSTRACT FROM AUTHOR]