Current Evidence of Anti–Tumor Necrosis Factor α Treatment Efficacy in Childhood Chronic Uveitis: A Systematic Review and Meta‐Analysis Approach of Individual Drugs

Simonini, Gabriele; Druce, Katie L; Cimaz, Rolando; Macfarlane, Gary J.; Jones, Gareth T

doi:10.1002/acr.22214

Cited by 99 publications

(89 citation statements)

References 46 publications

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“…However, in neither study was it possible to extract specific outcomes in the subset of patients who received ADA as first-line biologic treatment. In a metaanalysis including 5 studies of ADA, improvement in intraocular inflammation was reported in 87% of 31 patients with JIA, but again, the number of biologics-naive patients was not specified, and data on remission were available only for a few cases 9 . The only available study in which ADA was …”

Section: Discussionmentioning

confidence: 99%

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

Cecchin

Zannin²,

Ferrari³

et al. 2018

J Rheumatol

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Objective.Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years.Methods.Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics.Results.Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX.Conclusion.At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

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Section: Discussionmentioning

confidence: 99%

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

Cecchin

Zannin²,

Ferrari³

et al. 2018

J Rheumatol

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“…Etanercept is not recommended Legend: bd twice daily, GI gastro-intestinal, od once daily, po by mouth, sc subcutaneous in patients with JIA-U. A meta-analysis including 229 children with JIA-U has shown that infliximab and adalimumab have similar efficacy and both are superior to etanercept [61]. However, during 40 months' follow-up, uveitis more commonly remained in remission in those treated with adalimumab compared with infliximab (60 % vs 18.8 % respectively) [62].…”

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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“…A recently published systematic review by Simonini and colleagues 96 assessed the effectiveness of antiTNF drugs for childhood uveitis. To be included, studies had to include patients with autoimmune uveitis refractory to topical and/or systemic steroids and at least one immunosuppressive therapy (e.g.…”

Section: Adverse Eventsmentioning

confidence: 99%

“…The registry does not appear to include patients from the UK. Other evidence such as case series, open-label trials, a systematic review 96 and data from an Italian registry were included to provide evidence for the effectiveness of adalimumab in JIA-associated uveitis (see JIA-associated uveitis of this assessment report for details of these).…”

Section: Review Of Abbvie Company Evidence Submission For Adalimumabmentioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

Shepherd

Cooper²,

Harris³

et al. 2016

Health Technol Assess

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BackgroundJuvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated.ObjectiveTo assess the clinical effectiveness and cost-effectiveness of four biologic DMARDs [etanercept (Enbrel®, Pfizer), abatacept (Orencia®, Bristol-Myers Squibb), adalimumab (Humira®, AbbVie) and tocilizumab (RoActemra®, Roche) – with or without methotrexate where indicated] for the treatment of JIA (systemic or oligoarticular JIA are excluded).Data sourcesElectronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and the Database of Abstracts of Reviews of Effects were searched for published studies from inception to May 2015 for English-language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence.Review methodsSystematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost–utility decision-analytic model was developed to compare the estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base-case time horizon was 30 years and the model took a NHS perspective, with costs and benefits discounted at 3.5%.ResultsFour placebo-controlled randomised controlled trials (RCTs) met the inclusion criteria for the clinical effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi)-30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar, with fewer disease flares and greater proportions of ACR Pedi-50 and -70 responses among participants randomised to continued biologic DMARDs. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that, generally, ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between the treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality-of-life studies were included, one of which informed the cost–utility model. The incremental cost-effectiveness ratios (ICERs) for adalimumab, etanercept and tocilizumab versus methotrexate were £38,127, £32,526 and £38,656 per quality-adjusted life year (QALY), respectively. The ICER for abatacept versus methotrexate as a second-line biologic was £39,536 per QALY.LimitationsThe model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs, and clinical evidence for specific JIA subtypes is limited.ConclusionsBiologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA who have had an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow-up are needed to establish comparative effectiveness. RCTs for JIA subtypes for which evidence is lacking are also required.Study registrationThis study is registered as PROSPERO CRD42015016459.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Current Evidence of Anti–Tumor Necrosis Factor α Treatment Efficacy in Childhood Chronic Uveitis: A Systematic Review and Meta‐Analysis Approach of Individual Drugs

Cited by 99 publications

References 46 publications

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis-associated uveitis

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

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