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      The Management of Acute Anterior Uveitis Complicating Spondyloarthritis: Present and Future

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          Abstract

          Spondyloarthropathies (SpA) encompass a group of chronic inflammatory diseases sharing common genetic and clinical features, including the association with HLA-B27 antigen, the involvement of both the axial and the peripheral skeleton, the presence of dactylitis, enthesitis, and typical extra-articular manifestations such as psoriasis, inflammatory bowel disease, and acute anterior uveitis (AAU). The latter is commonly reported as a noninfectious acute inflammation of the anterior uveal tract and its adjacent structures. AAU may affect more than 20% of SpA patients representing the most common extra-articular manifestation of the disease. Considering the potential consequences of untreated AAU, early diagnosis and aggressive treatment are crucial to avoid complications of remittent or chronic eye inflammation, such as visual loss and blindness. The management of SpA has dramatically improved over the last decades due to the development of new treat-to-target strategies and to the introduction of biologic disease modifying antirheumatic drugs (bDMARDs), particularly tumor necrosis factor alpha inhibitors (TNFis), currently used for the treatment of nonresponder patients to conventional synthetic agents. Along with the improvement of musculoskeletal features of SpA, bDMARDs provided an additional effect also in the management of AAU in those patients who are failures to topical and systemic conventional therapies. Nowadays, five TNFis, one interleukin-17, and one interleukin 12/23 blocker are licensed for the treatment of SpA, with different proven efficacy in preventing and treating ocular involvement. The aim of this review is to summarize the current options and to analyze the future perspectives for the management of SpA-associated AAU.

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          Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors

          Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors.
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            Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

            Objective Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.
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              Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study.

              To determine the incidence and prevalence of uveitis in a large, well-defined population in Northern California. Cross-sectional study using retrospective database and medical record review. A group of 2070 people within 6 Northern California medical center communities (N = 731 898) who had a potential diagnosis of uveitis. The patient database of a large health maintenance organization (2 805 443 members at time of the study) was searched for all patients who, during a 12-month period, had the potential diagnosis of uveitis. Detailed quarterly gender- and age-stratified population data were available. Medical records of patients who potentially had uveitis and who were members of the 6 target communities were reviewed by 2 uveitis subspecialists to confirm the diagnosis of uveitis and to establish time of onset. Demographic and clinical data were gathered for patients meeting the clinical definition of uveitis. Incidence rates were calculated by using a dynamic population model. Prevalence rates were based on the mid-study period population. Presence and date of onset of uveitis. At midstudy, the population for the 6 communities was 731 898. During the target period, 382 new cases of uveitis were diagnosed; 462 cases of uveitis were diagnosed before the target period. These data yielded an incidence of 52.4/100 000 person-years and a period prevalence of 115.3/100 000 persons. The incidence and prevalence of disease were lowest in pediatric age groups and were highest in patients 65 years or older (P<0.0001). The prevalence of uveitis was higher in women than in men (P<0.001), but the difference in incidence between men and women was not statistically significant. Comparison between the group of patients who had onset of uveitis before the target period (ongoing uveitis) and the entire cohort of uveitis patients showed that women had a higher prevalence of ongoing uveitis than men and that this difference was largest in the older age groups (P<0.001). In this largest population-based uveitis study in the United States to date, the incidence of uveitis was approximately 3 times that of previous U.S. estimates and increased with the increasing age of patients. Women had a higher prevalence of uveitis than men, and the largest differences were in older age groups.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                14 October 2018
                : 2018
                : 9460187
                Affiliations
                1Department of Rheumatology, Gaetano Pini Institute, Milan, Italy
                2Department of Clinical Sciences and Health Community, University of Milan, Division of Rheumatology, Gaetano Pini Institute, Milan, Italy
                3Department of Ophthalmology, Scientific Institute San Raffaele, Milan, Italy
                Author notes

                Academic Editor: Hiroshi Tanaka

                Author information
                http://orcid.org/0000-0001-6530-1080
                http://orcid.org/0000-0002-1051-8511
                Article
                10.1155/2018/9460187
                6204187
                30406148
                1ec4106c-d9c9-4d9e-a6a4-f43cf05b3568
                Copyright © 2018 Martina Biggioggero et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 June 2018
                : 5 September 2018
                : 26 September 2018
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