A randomised controlled trial of the clinical effectiveness, safety and cost-effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial)

Ramanan, Athimalaipet V; Dick, Andrew D.; Benton, Diana; Compeyrot-Lacassagne, Sandrine; Dawoud, Dalia; Hardwick, Ben; Hickey, Helen; Hughes, Dyfrig; Jones, Ashley P; Woo, Patricia; Edelsten, Clive; Beresford, Michael W.

doi:10.1186/1745-6215-15-14

Cited by 95 publications

(75 citation statements)

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“…35,36 The ongoing SYCAMORE trial has been investigating the clinical effectiveness and safety of dual adalimumab and methotrexate treatment of JIA associated uveitis. 6 Our results have shown no new flares or worsening of visual acuity and only two patients had monocular visual loss, which was already present before starting adalimumab treatment. Similar findings have been reported by several reports.…”

Section: Discussionsupporting

confidence: 48%

“…5 Usually, it is diagnosed within the first seven years after the onset of arthritis; however, structural damage is present in 30 to 50% of children when JIA diagnosis is established. 6 Regular ophthalmological screening is recommended in these patients, particularly in certain JIA subtypes, to prevent visual loss. 4,7,8 Without adequate treatment, chronic inflammation might lead to severe irreparable damage and structural changes with serious complications (posterior synechiae, band keratopathy, cataract, glaucoma, Outcome of JIA Associated Uveitis Patients hypotonic, or macular edema) as well as blindness which may have additional impact on quality of life.…”

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confidence: 99%

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Outcome of Juvenile Idiopathic Arthritis Associated Uveitis in Two Disease Subtypes

Lazarević

2017

Arch Rheumatol

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Objectives: This study aims to evaluate the efficacy of adalimumab as a first line biologic agent in specific subtypes of juvenile idiopathic arthritis (JIA) patients with associated uveitis. Patients and methods:We retrospectively analyzed the data of 11 JIA patients (8 males, 3 females; mean age 14.5 years; range 9 to 18 years) with associated uveitis treated with biologic therapy. All patients were diagnosed as oligoarticular/extended oligoarticular or enthesitis-related JIA subtypes, treated with methotrexate, and had active or previous history of uveitis for which adalimumab was prescribed. We tested all patients for anti-nuclear antibody presence and human leukocyte antigen genotype. We assessed disease activity and therapy efficacy by American College of Rheumatology 50%, 70%, and 100% improvement criteria. We evaluated uveitis activity by slit-lamp biomicroscopy and recorded adverse events. Results: Of the JIA patients, three (27.27%) had oligoarticular/extended oligoarticular JIA and eight (72.73%) had enthesitis-related arthritis. Anti-nuclear antibody positivity was present in 27.27% (all females) while human leukocyte antigen-B51 was determined in 62.5% and human leukocyte antigen-B27 in 12.5% of patients. Mean uveitis duration before adalimumab introduction was 12.3 months. After two years of follow-up, there were no relapses of uveitis and visual acuity was stable while on adalimumab and methotrexate treatment. All patient were gradually tapered and discontinued treatment with topical steroids. Disease activity improved and seven patients (63.64%) achieved American College of Rheumatology 100% response rate (attained remission), while four patients (36.36%) achieved American College of Rheumatology 70% response rate. Conclusion: Anti-nuclear antibody positivity with oligoarticular/extended oligoarticular and enthesitis-related arthritis JIA subtypes, which are known for their high risk to develop uveitis, may benefit from adalimumab as a first line anti-tumor necrosis factor agent.

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Section: Discussionsupporting

confidence: 48%

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confidence: 99%

Outcome of Juvenile Idiopathic Arthritis Associated Uveitis in Two Disease Subtypes

Lazarević

2017

Arch Rheumatol

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“…The greatest evidence, thus far derived from cohort studies and with RCTs underway, supports the use of adalimumab in treatment of JIA-U. A doubleblind, placebo-controlled RCT of adalimumab was stopped early due to efficacy after randomising 90 patients [59]. Analysis of the primary endpoint ("time to treatment failure") showed a positive effect in favour of adalimumab with a hazard ratio of 0.27 (95 % CI 0.13-0.52, p < 0.0001).…”

Section: Biologic Drugsmentioning

confidence: 99%

Juvenile idiopathic arthritis-associated uveitis

Sen

Ramanan

2017

Best Practice & Research Clinical Rheumatology

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Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4 + T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.

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“…Only a prospective controlled trial will have the power to prove the efficacy of ADA. Such a study is currently running, but the results are not published yet (32).…”

mentioning

confidence: 99%

Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry

Foeldvari

Becker

Horneff

2015

Arthritis Care & Research

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ObjectiveUveitis is a major extraarticular quality of life–restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX).MethodsPatients’ characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated.ResultsUveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95% confidence interval 1.58–2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient‐years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient‐years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient‐years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3–3.8) while taking etanercept and 1.8 years (IQR 1.8–2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3–10.0) in the etanercept cohort and 4.8 years (IQR 1.0–5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis.ConclusionPatients with a history of uveitis had higher risks for uveitis events while taking both etanercept and adalimumab. Methotrexate turned out to be protective. Few patients developed a first uveitis event while taking etanercept, while the rate is comparable to that with MTX. Uveitis may not be attributed to be an adverse drug reaction to etanercept.

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A randomised controlled trial of the clinical effectiveness, safety and cost-effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial)

Cited by 95 publications

References 54 publications

Outcome of Juvenile Idiopathic Arthritis Associated Uveitis in Two Disease Subtypes

Outcome of Juvenile Idiopathic Arthritis Associated Uveitis in Two Disease Subtypes

Juvenile idiopathic arthritis-associated uveitis

Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry

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