(2016). Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet, 388(10050) Link to publication record in Explore Bristol Research PDF-document This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at http://www.sciencedirect.com/science/article/pii/S0140673616313393. Please refer to any applicable terms of use of the publisher., University of Bristol -Explore Bristol Research General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms

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.

In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.

Treatment with adalimumab is an effective and safe option, reducing the need for oral corticosteroid and conventional immunosuppressive therapy.

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 AE 17.1 mg/day at week 0 (n ¼ 359) to 1.5 AE 3.9 mg/day at week 150 (n ¼ 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 ¼ 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.

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Purpose To describe distinctive stages of Vogt-Koyanagi-Harada (VKH) disease: initial-onset acute versus chronic recurrent disease. Methods A comprehensive literature review regarding stages and clinical presentations of VKH disease was conducted. Results Despite a list of signs that has been described as characteristic features of early or late phases of VKH disease, the current classification -developed by an international committee and published in 2001- does not consider a distinction regarding the time from onset of disease symptoms, and specific findings observed at certain time point from the symptoms presentation and outcomes related to the stage of VKH disease. In that sense, chronic recurrent VKH disease is more refractory to treatment and is associated with a higher rate of complications. Accordingly, this subset of VKH patients has poorer functional and anatomical outcomes than patients with an initial-onset acute disease. Conclusions An early clear distinction of VKH phenotype [Initial-onset acute versus chronic recurrent disease] should be considered in each clinical scenario, evaluating the delay in diagnosis and the clinical presentation, since it may help clinicians to perform a correct disease prognosis categorization and thus to make treatment decisions in terms of potential refractoriness or expected clinical outcomes.

Background Appraisals of Vogt-Koyanagi-Harada disease (VKH) have become progressively more complete, since its first description in 1906. The availability of new investigational methods has improved our knowledge of the immunopathology, clinicopathology, diagnosis, and management of VKH disease. This review aimed to describe some of the steps that led to better characterization of VKH as a clinical entity. Methods We searched on PubMed for articles that described the history of VKH disease and analyzed the progress in disease appraisal with new investigational and imaging methods. In particular, we searched for articles that investigated the clinicopathology, diagnosis, and management of VKH. Findings The following developments were considered essential for improving the appraisal and understanding of VKH: (1) the history of the disease, (2) immunopathological mechanisms, (3) clinicopathology, (4) the importance of distinguishing initial-onset from chronic disease, (5) relevant imaging modalities, among which indocyanine green angiography is crucial, (6) diagnostic criteria that facilitate early diagnosis, and (7) the need for early, prolonged, aggressive treatment that combines steroidal and non-steroidal immunosuppression. Conclusion Based on these findings, the definition of VKH has improved. VKH disease starts in the choroidal stroma and later involves other structures when it is not diagnosed and treated early. Indocyanine green angiography and enhanced depth imaging optical coherence tomography facilitate early diagnosis and precise monitoring of choroidal inflammation. ICGA is clearly the gold standard for appraisals and follow-ups in VKH disease, however EDI-OCT should be especially considered in those areas where ICGA is not fully available. These modalities have contributed substantially to a “cure” for VKH, when treatment is introduced within the therapeutic window of opportunity.