Juvenile idiopathic arthritis-associated uveitis

Sen, Ethan S; Ramanan, Athimalaipet V

doi:10.1016/j.berh.2018.01.002

Cited by 52 publications

(46 citation statements)

References 105 publications

(51 reference statements)

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“…[4][5][6][7][8] In such patients, mono clonal TNF inhibitors, including adalimumab, are often effective. [9][10][11][12] However, 30-40% 13 of patients are refractory to both methotrexate and TNF inhibitors and are there fore at great risk of significant ocular complications and blindness.…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Ramanan

Dick

Guly

et al. 2020

The Lancet Rheumatology

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Background Uveitis associated with juvenile idiopathic arthritis is a cause of major ocular morbidity. A substantial proportion of children are refractory to systemic methotrexate and TNF inhibitors. Our aim was to study the safety and efficacy of tocilizumab in children with juvenile idiopathic arthritis-associated uveitis refractory to both methotrexate and TNF inhibitors. Methods This multicentre, single-arm, phase 2 trial was done following a Simon's two-stage design at seven tertiary hospital sites in the UK. Patients aged 2-18 years with active juvenile idiopathic arthritis-associated uveitis were eligible. All patients had been on a stable dose of methotrexate for at least 12 weeks and had not responded to treatment with a TNF inhibitor. Patients weighing 30 kg or more were treated with 162 mg subcutaneous tocilizumab every 2 weeks for 24 weeks, and participants weighing less than 30 kg were treated with 162 mg every 3 weeks for 24 weeks. The primary outcome was treatment response defined as a two-step decrease, or decrease to zero, from baseline in the level of inflammation (anterior chamber cells) at week 12, per the standardisation of uveitis nomenclature criteria. A phase 3 trial would be justified if more than seven patients responded to treatment. An interim analysis was planned to assess whether the trial would be stopped for futility, with futility defined as two or fewer treatment responses among ten participants. Adverse events were collected up to 30 calendar days after treatment cessation. The primary analysis was done in the intention-to-treat population and the safety analysis was done in all patients who started the treatment. This trial is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN95363507) and EU Clinical Trials Register (EudraCT 2015-001323-23). Findings 22 participants were enrolled to the trial between Dec 3, 2015, and March 9, 2018, and 21 participants received treatment. One participant was found to be ineligible immediately after enrolment and was therefore withdrawn. Seven of 21 (median unbiased estimate of proportion 34% [95% CI 25-57]) responded to treatment (p=0•11). Safety results were consistent with the known safety profile of tocilizumab. Interpretation The primary endpoint was not met, and thus the results do not support a phase 3 trial of tocilizumab in patients with juvenile idiopathic arthritis-associated uveitis. Importantly, data on the use of tocilizumab in clinical practice is now captured in national registries. Despite this trial not meeting the threshold required to justify a larger phase 3 trial, several patients responded to treatment; as such, tocilzumab might still be a therapeutic option in some children with uveitis refractory to anti-TNF drugs, given the absence of other treatment options.

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Section: Introductionmentioning

confidence: 99%

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Ramanan

Dick

Guly

et al. 2020

The Lancet Rheumatology

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“…JIA-associated uveitis commonly manifest as chronic anterior uveitis, which is often clinically silent, but can lead to serious sight-threatening complications. This form of uveitis is typically associated with oligoarticular and RF-negative polyarticular arthritis with particular risk for girls who develop JIA within 3 years of age with ANA positivity [1,3,[8][9][10]. In contrast, boys with ERA HLA-B27 positivity develop most frequently acute anterior uveitis, which is symptomatic, unilateral and episodic [3,8,10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Treatment includes topical therapies with cycloplegics, steroids and NSAID and systemic immunosuppressive therapies based on steroids, synthetic DMARDs such as methotrexate or biologic drugs such as adalimumab and infliximab [8,12].…”

Section: Introductionmentioning

confidence: 99%

Juvenile idiopathic arthritis-associated uveitis: a retrospective analysis from a centre of South Italy

et al. 2019

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Purpose To investigate the clinical and laboratory characteristics of the children affected by juvenile idiopathic arthritis (JIA) who developed uveitis. Methods In this retrospective study, we have examined data of 109 patients aged from 3 to 16 years, affected by JIA and followed at Paediatrics Rheumatology Clinic and Ophthalmology Clinic of University Hospital of Messina in the period from 2007 to 2017. The main outcome measures were clinical and laboratory findings related to JIA and ocular involvement. The prevalence of ocular signs and symptoms was determined and correlated with age. Results Twenty-one (19.3%) subjects developed uveitis. Two different peaks of age with ocular involvement were registered. The first occurred between 4 and 6 years and the second between 10 and 12 years. All subjects in the first group resulted to be female, presented oligoarticular arthritis and chronic anterior uveitis. In the second group, the 84% of patients were male with different types of JIA and acute anterior uveitis. The prevalence of ocular complications was higher in the first group. Conclusions Two peaks of age emerged and were characterized by different clinical outcomes of arthritis and ocular involvement. The first occurred between 4 and 6 years and interested females affected by oligoarticular JIA who develop chronic anterior uveitis. The second appeared at 10-12 years and interested older males affected by different types of JIA with acute anterior uveitis. Early diagnosis and cooperation between paediatric rheumatologist and ophthalmologist are of great importance in the proper management of JIA children with uveitis.

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“…JIA is a complicated disease, which often induces arthritis . Seven subtypes of JIA are defined, based on the number of joints involved in the first 6 months of disease and the extra‐articular involvement, including oligoarticular JIA (<5 joints), polyarticular JIA (≥5 joints) and systemic JIA, and uveitis is the most frequent extra‐articular manifestation associated with JIA …”

Section: Introductionmentioning

confidence: 99%

Adult outcome of juvenile idiopathic arthritis: A nationwide population‐based retrospective cohort study in Taiwan

et al. 2019

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Objective To clarify the development of juvenile idiopathic arthritis (JIA) to adult‐onset autoimmune diseases in a population‐based study in Taiwan. Methods We analyzed data of 107 433 children born between 1990 and 1997 from the National Taiwan Health Insurance Database. There were 262 JIA patients and 107 171 individuals without JIA who were selected and followed up until December 2013 to investigate their outcomes of adult‐onset autoimmune diseases after reaching 16 years of age. The adjusted hazard ratios (aHRs) including 95% confidence intervals (95% CI) of adult‐onset autoimmune diseases were calculated using the Cox proportional regression model among different age groups. Results The incidence rate for patients with a history of JIA was 83.56 per 105 person‐months for rheumatoid arthritis (RA), 16.61 for systemic lupus erythematosus (SLE), 58.39 for ankylosing spondylitis (AS), and 33.26 for psoriatic diseases. The aHRs were 29.60 for any autoimmune disease, 129.52 for RA, 10.01 for SLE, 49.62 for AS, and 8.20 for psoriatic diseases. Compared with non‐JIA individuals, the aHRs of adult‐onset autoimmune diseases were 34.87 (95% CI: 4.85‐250.62) at the onset age of 3‐5 years, 12.01 (95% CI: 2.99‐48.26) at the age of 6‐10 years, and 45.80 (95% CI: 29.69‐70.64) at the age of 11‐15 years. Conclusion Children with JIA were at an increased risk of developing RA, AS, psoriatic disease, and SLE in adulthood.

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Juvenile idiopathic arthritis-associated uveitis

Cited by 52 publications

References 105 publications

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Juvenile idiopathic arthritis-associated uveitis: a retrospective analysis from a centre of South Italy

Adult outcome of juvenile idiopathic arthritis: A nationwide population‐based retrospective cohort study in Taiwan

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