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. 2022 Oct 14;10(10):CD013818.
doi: 10.1002/14651858.CD013818.pub2.

Tumor necrosis factor (TNF) inhibitors for juvenile idiopathic arthritis-associated uveitis

William D Renton #  1 , Jennifer Jung #  2 , Alan G Palestine  2
Affiliations

Tumor necrosis factor (TNF) inhibitors for juvenile idiopathic arthritis-associated uveitis

William D Renton et al. Cochrane Database Syst Rev. .

Abstract

Background: Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by intraocular inflammation. Current treatment for JIA-associated uveitis (JIA-U) is largely based on physician experience, observational evidence and consensus guidelines, resulting in considerable variations in practice. OBJECTIVES: To evaluate the effectiveness and safety of tumor necrosis factor (TNF) inhibitors used for treatment of JIA-U.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We last searched the electronic databases on 3 February 2022.

Selection criteria: We included randomized controlled trials (RCTs) comparing TNF inhibitors with placebo in participants with a diagnosis of JIA and uveitis who were aged 2 to 18 years old.

Data collection and analysis: We used standard Cochrane methodology and graded the certainty of the body of evidence for seven outcomes using the GRADE classification.

Main results: We included three RCTs with 134 participants. One study conducted in the USA randomized participants to etanercept or placebo (N = 12). Two studies, one conducted in the UK (N = 90) and one in France (N = 32), randomized participants to adalimumab or placebo. All studies were at low risk of bias. Initial pooled estimates suggested that TNF-inhibitors may result in little to no difference on treatment success defined as 0 to trace cells on Standardization of Uveitis Nomenclature (SUN)-grading; or two-step decrease in activity based on SUN grading (estimated risk ratio (RR) 0.66; 95% confidence interval (CI) 0.21 to 2.10; 2 studies; 43 participants; low-certainty evidence) or treatment failure defined as a two-step increase in activity based on SUN grading (RR 0.31; 95% CI 0.01 to 7.15; 1 study; 31 participants; low-certainty evidence). Further analysis using the individual trial definitions of treatment response and failure suggested a positive treatment effect of TNF inhibitors; a RR of treatment success of 2.60 (95% CI 1.30 to 5.20; 3 studies; 124 participants; low-certainty evidence), and RR of treatment failure of 0.23 (95% CI 0.11 to 0.50; 3 studies; 133 participants). Almost all the evidence was on adalimumab and the evidence on etanercept was very limited. For secondary outcomes, one study suggests that adalimumab may have little to no effect on risk of recurrence after induction of remission at three months (RR 2.50, 95% CI 0.31 to 20.45; 90 participants; very low-certainty evidence) and visual acuity, but the evidence is very uncertain; mean difference in longitudinal logMAR score change over six months was -0.01 (95% CI -0.06 to 0.03) and -0.02 (95% CI -0.07 to 0.03) using the best and worst logMAR measurement, respectively (low-certainty evidence). Low-certainty evidence from one study suggested that adalimumab treatment results in reduction of topical steroid doses at six months (hazard ratio 3.58; 95% CI 1.24 to 10.32; 74 participants who took one or more topical steroid per day at baseline). Adverse events, including injection site reactions and infections, were more common in the TNF inhibitor group. Serious adverse events were uncommon.

Authors' conclusions: Adalimumab appears to increase the likelihood of treatment success and decrease the likelihood of treatment failure when compared with placebo. The evidence was less conclusive about a positive treatment effect with etanercept. Adverse events from JIA-U trials are in keeping with the known side effect profile of TNF inhibitors. Standard validated JIA-U outcome measures are required to homogenize assessment and to allow for comparison and analysis of multiple datasets.

PubMed Disclaimer

Conflict of interest statement

JJ none reported.

AP serves as a Co‐investigator for Cochrane Eyes and Vision US Satellite, which is supported by grant UG1 EY020522 from the National Eye Institute, National Institutes of Health, USA.

WR is a site principal investigator for ADJUST, an ongoing study.

Figures

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Study flow diagram.
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1.1
1.1. Analysis
Comparison 1: Tumor necrosis factor (TNF) inhibitors versus placebo (per review protocol), Outcome 1: Treatment success defined as 0 to trace cells; or 2‐step decrease in activity using in SUN anterior chamber (AC) cell grading
1.2
1.2. Analysis
Comparison 1: Tumor necrosis factor (TNF) inhibitors versus placebo (per review protocol), Outcome 2: Treatment failure defined as 2‐step increase in SUN anterior chamber (AC) cell grading
1.3
1.3. Analysis
Comparison 1: Tumor necrosis factor (TNF) inhibitors versus placebo (per review protocol), Outcome 3: Systemic adverse events
2.1
2.1. Analysis
Comparison 2: Tumor necrosis factor (TNF) inhibitors versus placebo (per individual study protocol), Outcome 1: Treatment success/response defined by individual study
2.2
2.2. Analysis
Comparison 2: Tumor necrosis factor (TNF) inhibitors versus placebo (per individual study protocol), Outcome 2: Treatment failure/flare defined by individual study
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013818

References

References to studies included in this review

ADJUVITE {published data only}
    1. 2010-019441-26. Adalimumab dans l’Arthrite Juvénile Idiopathique pour le traitement de l’UVéITE (étude ADJUVITE). https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-019441-26/FR (first received 14 June 2010).
    1. NCT01385826. Effect of adalimumab for the treatment of uveitis in juvenile idiopathic arthritis. https://clinicaltrials.gov/show/NCT01385826 (first received 30 June 2011).
    1. Quartier P, Baptiste A, Despert V, Allain-Launay E, Koné-Paut I, Belot A, et al. ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. Annals of the Rheumatic Diseases 2018;77(7):1003-11. - PubMed
    1. Quartier P, Despert V, Poignant S, Baptiste A, Elie C, Kone-Paut I, et al. Adjuvite: a double-blind, randomized, placebo-controlled trial of Adalimumab in juvenile idiopathic arthritis associated uveitis. Pediatric Rheumatology 2017;15(Suppl 1):455.
    1. Quartier P, Despert V, Poignant S, Elie C, Kone-Paut I, Belot A, et al. Adjuvite: a double-blind, randomized, placebo-controlled trial of adalimumab in juvenile idiopathic arthritis associated uveitis. Annals of the Rheumatic Diseases 2016;75:273. - PubMed
Smith 2005 {published data only}
    1. Liu DT, Chan A. Assessment of inflammatory response in a study of uveitis associated with juvenile idiopathic arthritis: comment on the article by Smith et al. Arthritis and Rheumatism 2005;53(6):986; author reply 986-7. - PubMed
    1. NCT00001862. TNRF:Fc to treat eye inflammation in juvenile rheumatoid arthritis [The safety and efficacy of a tumor necrosis factor receptor fusion protein on uveitis associated with juvenile rheumatoid arthritis]. https://clinicaltrials.gov/ct2/show/NCT00001862 (first received 4 November 1999).
    1. Smith JA, Thompson DJ, Whitcup SM, Suhler E, Clarke G, Smith S, et al. A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis and Rheumatism 2005;53(1):18‐23. - PubMed
    1. Smith JA, Thompson DJ, Whitcup SM, Suhler E, Clarke G, Smith S, et al. Reply. Arthritis and Rheumatism 2005;53:986-7. - PubMed
SYCAMORE {published data only (unpublished sought but not used)}
    1. Culeddu G, Welton N J, Hughes D. Comparison of regression methods for the cost effectiveness analysis of clinical trials with a small population size: the sycamore and folated trials. Trials 2017;18(Suppl 1):200.
    1. EUCTR2010-021141-41-GB. Randomised control 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. https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-021141-41/GB (first received 30 March 2011). - PMC - PubMed
    1. Horton S, Jones AP, Guly CM, Hardwick B, Beresford MW, Lee RW, et al. Adalimumab in juvenile idiopathic arthritis-associated uveitis: 5-year follow-up of the Bristol participants of the SYCAMORE Trial. American Journal of Ophthalmology 2019;207:170-4. - PubMed
    1. Hughes DA, Culeddu G, Plumpton CO, Wood E, Dick AD, Jones AP, et al. Cost-effectiveness analysis of adalimumab for the treatment of uveitis associated with juvenile idiopathic arthritis. Ophthalmology 2019;126(3):415-24. - PubMed
    1. ISRCTN10065623. The clinical effectiveness, safety and cost effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis. https://www.isrctn.com/ISRCTN10065623 (first received 2 September 2011). - PMC - PubMed

References to studies excluded from this review

Alexeeva 2018 {published data only}
    1. Alexeeva E, Dvoryakovskaya T, Denisova R, Nikishina I, Zholobova E, Malievskiy V, et al. A randomised, double-blind, parallel study to compare rates of remission (inactive disease) in patients with JIA on MTX treatment alone versus a combination of MTX and etanercept. Annals of the Rheumatic Diseases 2018;77:486.
EUCTR2010‐020423‐51‐DE {published data only}
    1. EUCTR2010-020423-51-DE. Remission induction by etanercept in enthesitis related arthritis JIA-patients (juvenile undifferentiated spondylarthropathy). https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-020423-51/DE (first received 27 September 2010).
EUCTR2019‐000119‐10‐FR {published data only}
    1. EUCTR2019-000119-10-FR. A study of Baricitinib in children and young adults with JIA associated eye inflammation [An open-label, active-controlled, safety and efficacy study of oral baricitinib in patients from 2 years to less than 18 years old with active juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody positive uveitis]. https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000119-10/FR 2019;(first received 29 May 2019).
Mansour 2007 {published data only}
    1. Mansour AM. Adalimumab in the therapy of uveitis in childhood. British Journal of Ophthalmology 2007;91(3):274-6. - PMC - PubMed
Martin‐Varillas 2020 {published data only}
    1. Martin-Varillas JL, Calvo-Rio V, Sanchez-Bilbao L, Gonzalez-Mazon I, Torre-Salaberri I, Garcia Martos A, et al. Certolizumab therapy in refractory uveitis due to immune-mediated inflammatory diseases (IMID). multicenter study of 39 patients. Annals of the Rheumatic Diseases 2020;79(Suppl 1):384-5.
NCT00012506 {published data only}
    1. NCT00012506. The safety and efficacy of a tumor necrosis factor receptor fusion protein on uveitis associated with juvenile rheumatoid arthritis. https://clinicaltrials.gov/ct2/show/NCT00012506 (first received 12 March 2001).
Rabinovich 2010 {published data only}
    1. NCT00589628. Multi center prospective registry of infliximab use for childhood uveitis. https://clinicaltrials.gov/ct2/show/NCT00589628 (first received 10 January 2008).
    1. Rabinovich EC, Wootton J, Zemel , Imundo L, Weiss J, Abramson LS, et al. Prospective study of infliximab for treatment of pediatric uveitis. Arthritis and Rheumatism 2010;62:234.
Roberts 2022 {published data only}
    1. Roberts JE, Nigrovic PA, Lo MS, Chang MH. Weekly adalimumab, an effective alternative for refractory uveitis in children. Journal of Clinical Rheumatology 2022;28(1):e301-4. - PMC - PubMed
Romero 2017 {published data only}
    1. Romero ER, Galan RA, Almagro RM, Munoz A, Povedano J. Treatment of non-infectious uveitis: a comparative long-term study between biologic therapy with adalimumab and two conventional disease-modifying antirheumatic drugs. Arthritis and Rheumatology 2017;69(Suppl 10):S1609.
Ruchalla 2017 {published data only}
    1. Ruchalla E, Dürrheim B. Adalimumab can control uveitis within the framework of a juvenile idiopathic arthritis (JIA). Aktuelle Rheumatologie 2017;42(5):366-8.
Suhler 2005 {published data only}
    1. Suhler EB, Smith JR, Wertheim MS, Lauer AK, Kurz DE, Pickard TD, et al. A prospective trial of infliximab therapy for refractory uveitis: Preliminary safety and efficacy outcomes. Archives of Ophthalmology 2005;123(7):903-12. - PubMed
Thorne 2017 {published data only}
    1. Thorne JE. Adalimumab in the treatment of uveitis in juvenile idiopathic arthritis. New England Journal of Medicine 2017;376(17):1682-3. - PubMed
Tynjälä 2011 {published and unpublished data}
    1. NCT01015547. Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA). https://clinicaltrials.gov/ct2/show/NCT01015547 (first received 18 November 2009). - PubMed
    1. Tarkiainen M, Tynjala P, Vahasalo P, Kroger L, Aalto K, Lahdenne P. Health-related quality of life during early aggressive treatment in patients with polyarticular juvenile idiopathic arthritis: results from randomized controlled trial. Pediatric Rheumatology Online Journal 2019;17:80. - PMC - PubMed
    1. Tynjälä P, Vähäsalo P, Tarkiainen M, Kröger L, Aalto K, Malin M, et al. Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): A multicentre randomised open-label clinical trial. Annals of the Rheumatic Diseases 2011;70(9):1605-12. - PubMed

References to ongoing studies

ADJUST {published data only}
    1. Acharya NR, Ebert CD, Kelly NK, Porco TC, Ramanan AV, Arnold BF, et al. Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST—Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial. Trials 2020;21(1):887. - PMC - PubMed
    1. EUCTR2019-000412-29-GB. Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial (ADJUST). https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000412-29/GB (first received 25 March 2019).
    1. NCT03816397. Adalimumab in JIA-associated Uveitis Stopping Trial. https://clinicaltrials.gov/show/NCT03816397 (first received 25 January 2019).

Additional references

Angeles‐Han 2019
    1. Angeles-Han ST, Ringold S, Beukelman T, Lovell D, Cuello CA, Becker ML, et al. 2019 American College of Rheumatology/Arthritis foundation guideline for the screening, monitoring, and treatment of juvenile idiopathic arthritis-associated uveitis. Arthritis and Rheumatology 2019;71(6):864-77. - PMC - PubMed
Angeles‐Han 2019a
    1. Angeles-Han ST, Lo MS, Henderson LA, Lerman MA, Abramson L, Cooper AM, on behalf of Juvenile Idiopathic Arthritis Disease-Specific, Uveitis Subcommittee of the Childhood Arthritis Rheumatology, Research Alliance. Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans for Juvenile Idiopathic Arthritis-Associated and Idiopathic Chronic Anterior Uveitis. Arthritis Care & Research (Hoboken) 2019;71(4):482-91. - PMC - PubMed
Beutler 1985
    1. Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985;229(4716):869-71. - PubMed
Brunner 2018
    1. Brunner HI, Ruperto N, Tzaribachev N, Horneff G, Chasnyk VG, Panaviene V, on behalf of Paediatric Rheumatology International Trials Organisation, the Pediatric Rheumatology Collaborative Study Group. Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis: results of a multicentre, double-blind, randomised-withdrawal trial. Annals of the Rheumatic Diseases 2018;77(1):21-9. - PMC - PubMed
Cann 2018
    1. Cann M, Ramanan AV, Crawford A, Dick AD, Clarke SL, Rashed F, et al. Outcomes of non-infectious paediatric uveitis in the era of biologic therapy. Pediatric Rheumatology Online Journal 2018;16(1):51. - PMC - PubMed
Cassedy 2020
    1. Cassedy A, Altaye M, Andringa J, Cooper AM, Drews-Botsch C, Engelhard G Jr, et al. Assessing the validity and reliability of the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) questionnaire among children with uveitis. Arthritis Care & Research (Hoboken) 2020 Oct 21 [Epub ahead of print]. [DOI: 10.1002/acr.24491] - DOI - PubMed
Cecchin 2018
    1. Cecchin V, Zannin ME, Ferrari D, Pontikaki I, Miserocchi E, Paroli MP, et al. Longterm safety and efficacy of adalimumab andiInfliximab for uveitis associated with juvenile idiopathic arthritis. Journal of Rheumatology 2018;45(8):1167-72. - PubMed
Clarke 2016
    1. Clarke SL, Sen ES, Ramanan AV. Juvenile idiopathic arthritis-associated uveitis. Pediatric Rheumatology 2016;14(1):27. - PMC - PubMed
Consolaro 2016
    1. Consolaro A, Giancane G, Schiappapietra B, Davi S, Calandra S, Lanni S, et al. Clinical outcome measures in juvenile idiopathic arthritis. Pediatric Rheumatology Online Journal 2016;14(1):23. - PMC - PubMed
Constantin 2018
    1. Constantin T, Foeldvari I, Anton J, Boer J, Czitrom-Guillaume S, Edelsten C, et al. Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative. Annals of the Rheumatic Diseases 2018;77(8):1107-17. - PMC - PubMed
Cordero‐Coma 2015
    1. Cordero-Coma M, Sobrin L. Anti-tumor necrosis factor-α therapy in uveitis. Survey of Ophthalmology 2015;60(6):575-89. - PubMed
Covidence [Computer program]
    1. Covidence. Melbourne, Australia: Veritas Health Innovation, accessed 22 February 2022. Available at covidence.org.
Deeks 2019
    1. Deeks JJ, Higgins JP, Altman DG, editor(s). Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook.
Dick 1998
    1. Dick AD, Duncan L, Hale G, Waldmann H, Isaacs J. Neutralizing TNF-alpha activity modulates T-cell phenotype and function in experimental autoimmune uveoretinitis. Journal of Autoimmunity 1998;11(3):255-64. - PubMed
Fleisher 1990
    1. Fleisher LN, Ferrell JB, McGahan MC. Ocular inflammatory effects of intravitreally injected tumor necrosis factor-alpha and endotoxin. Inflammation 1990;14(3):325-35. - PubMed
Foeldvari 2019
    1. Foeldvari I, Klotsche J, Simonini G, Edelsten C, Angeles-Han ST, Bangsgaard R, et al. Proposal for a definition for response to treatment, inactive disease and damage for JIA associated uveitis based on the validation of a uveitis related JIA outcome measures from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Pediatric Rheumatology Online Journal 2019;17(1):66. - PMC - PubMed
Gerriets 2020
    1. Gerriets V, Bansal P, Khaddour K. Tumor Necrosis Factor (TNF) Inhibitors. www.ncbi.nlm.nih.gov/books/NBK482425/ (accessed 18 November 2020).
Glanville 2006
    1. Glanville JM, Lefebvre C, Miles JN, Camosso-Stefinovic J. How to identify randomized controlled trials in MEDLINE: ten years on. Journal of the Medical Library Association 2006;94(2):130-6. - PMC - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT. Hamilton (ON): McMaster University (developed by Evidence Prime), accessed prior to 18 November 2020. Available at gradepro.org.
Gregory 2013
    1. Gregory AC 2nd, Kempen JH, Daniel E, Kaçmaz RO, Foster CS, Jabs DA, et al. Risk factors for loss of visual acuity among patients with uveitis associated with juvenile idiopathic arthritis: the Systemic Immunosuppressive Therapy for Eye Diseases Study. Ophthalmology 2013;120(1):186-92. - PMC - PubMed
Heiligenhaus 2019
    1. Heiligenhaus A, Minden K, Tappeiner C, Baus H, Bertram B, Deuter C, et al. Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Seminars in Arthritis and Rheumatism 2019;49(1):43-55. - PubMed
Heiligenhaus 2020
    1. Heiligenhaus A, Klotsche J, Niewerth M, Horneff G, Ganser G, Haas JP, et al. Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany. Arthritis Research & Therapy 2020;22(1):81. - PMC - PubMed
Higgins 2019a
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch V, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook. - PMC - PubMed
Higgins 2019b
    1. Higgins JP, Savović J, Page MJ, Elbers RG, Sterne JA. Chapter 8: Assessing risk of bias in a randomized trial. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook.
Higgins 2019c
    1. Higgins JP, Eldridge S, Li T, editor(s). Chapter 23: Including variants on randomized trials. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook.
Horiuchi 2010
    1. Horiuchi T, Mitoma H, Harashima S, Tsukamoto H, Shimoda T. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology 2010;49(7):1215-28. - PMC - PubMed
Jabs 2005
    1. Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. American Journal of Ophthalmology 2005;140(3):509-16. - PMC - PubMed
Keystone 2010
    1. Keystone EC, Ware CF. Tumor necrosis factor and anti-tumor necrosis factor therapies. Journal of Rheumatology. Supplement 2010;85:27-39. - PubMed
Khera 2010
    1. Khera TK, Dick AD, Nicholson LB. Mechanisms of TNFα regulation in uveitis: focus on RNA-binding proteins. Progress in Retinal and Eye Research 2010;29(6):610-21. - PubMed
Khera 2012
    1. Khera TK, Copland DA, Boldison J, Lait PJ, Szymkowski DE, Dick AD, et al. Tumour necrosis factor-mediated macrophage activation in the target organ is critical for clinical manifestation of uveitis. Clinical and Experimental Immunology 2012;168(2):165-77. - PMC - PubMed
Leal 2019
    1. Leal I, Rodrigues FB, Sousa DC, Duarte GS, Romao VC, Marques-Neves C, et al. Anti-TNF drugs for chronic uveitis in adults-a systematic review and meta-analysis of randomized controlled trials. Frontiers in Medicine (Lausanne) 2019;6:104. - PMC - PubMed
Liu 2005
    1. Liu DT, Chan AY. Assessment of inflammatory response in a study of uveitis associated with juvenile idiopathic arthritis: comment on the article by Smith et al. Arthritis and Rheumatism 2005;53(6):986-7. - PubMed
Lovell 2000
    1. Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. New England Journal of Medicine 2000;342(11):763-9. - PubMed
Lovell 2008
    1. Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, on behalf of Pediatric Rheumatology Collaborative Study Group, Pediatric Rheumatology International Trials Organisation. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. New England Journal of Medicine 2008;359(8):810-20. - PubMed
Mastrangelo 2019
    1. Mastrangelo G, Foeldvari I, Anton J, Simonini G. Defining outcome measures in juvenile idiopathic arthritis associated uveitis by a systematic review analysis: do we need a consensus? Pediatric Rheumatology Online Journal 2019;17(1):40. - PMC - PubMed
McKenzie 2019
    1. McKenzie JE, Brennan SE, Ryan RE, Thomson HJ, Johnston RV. Chapter 9: Summarizing study characteristics and preparing for synthesis. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook.
Nesbitt 2007
    1. Nesbitt A, Fossati G, Bergin M, Stephens P, Stephens S, Foulkes R, et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflammatory Bowel Diseases 2007;13(11):1323-32. - PubMed
Nicolela 2020
    1. Nicolela Susanna F, Pavesio C. A review of ocular adverse events of biological anti-TNF drugs. Journal of Ophthalmic Inflammation and Infection 2020;10(1):11. - PMC - PubMed
Prakken 2011
    1. Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet 2011;377(9783):2138-49. - PubMed
RevMan Web 2019 [Computer program]
    1. Review Manager Web (RevMan Web). The Cochrane Collaboration, 2019, Available at: revman.cochrane.org.
Rosenberg 2004
    1. Rosenberg KD, Feuer WJ, Davis JL. Ocular complications of pediatric uveitis. Ophthalmology 2004;111(12):2299–306. - PubMed
Rothova 1996
    1. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. British Journal of Ophthalmology 1996;80(4):332-6. - PMC - PubMed
Santos Lacomba 2001
    1. Santos Lacomba M, Marcos Martín C, Gallardo Galera JM, Gómez Vidal MA, Collantes Estévez E, Ramírez Chamond R, et al. Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis. Ophthalmic Research 2001;33(5):251-5. - PubMed
Saurenmann 2006
    1. Saurenmann RK, Levin AV, Feldman BM, Laxer RM, Schneider R, Silverman ED. Risk of new-onset uveitis in patients with juvenile idiopathic arthritis treated with anti-TNFalpha agents. Journal of Pediatrics 2006;149(6):833-6. - PubMed
Schünemann 2019
    1. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing ‘Summary of findings’ tables and grading the certainty of the evidence. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook.
Sen 2017
    1. Sen ES, Ramanan AV. Juvenile idiopathic arthritis-associated uveitis. Best Practice and Research: Clinical Rheumatology 2017;31(4):517-34. - PubMed
Simonini 2013
    1. Simonini G, Paudyal P, Jones GT, Cimaz R, Macfarlane GJ. Current evidence of methotrexate efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach. Rheumatology 2013;52(5):825-31. - PubMed
Simonini 2014
    1. Simonini G, Druce K, Cimaz R, Macfarlane GJ, Jones GT. Current evidence of anti-tumor necrosis factor alpha treatment efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach of individual drugs. Arthritis Care & Research 2014;66(7):1073-84. - PubMed
Smith 2021
    1. Smith JR, Matthews JM, Conrad D, Hall AJ, Niederer RL, Singh-Grewal D, on behalf of New Zealand Juvenile Idiopathic Arthritis-Uveitis Working Group. Recommendations for the management of childhood juvenile idiopathic arthritis-type chronic anterior uveitis. Clinical & Experimental Ophthalmology 2021;49(1):38-45. - PubMed
Solebo 2019
    1. Solebo A L, Barry RJ, Keane PA, Rahi JS, Denniston AK. Under-utilisation of reproducible, child appropriate or patient reported outcome measures in childhood uveitis interventional research. Orphanet Journal of Rare Diseases 2019;14(1):125. - PMC - PubMed
Solebo 2020
    1. Solebo AL, Rahi JS, Dick AD, Ramanan AV, Ashworth J, Edelsten C, on behalf of the Poig Uveitis Delphi Group. Areas of agreement in the management of childhood non-infectious chronic anterior uveitis in the UK. British Journal of Ophthalmology 2020;104(1):11-6. - PubMed
SUN 2005
    1. Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. American Journal of Ophthalmology 2005;140(3):509-16. - PMC - PubMed
SUN Working Group 2021
    1. Standardization of Uveitis Nomenclature Working Group. Classification Criteria for Juvenile Idiopathic Arthritis-Associated Chronic Anterior Uveitis. American Journal of Ophthalmology 2021;228:192-7. - PMC - PubMed
Tynjala 2007
    1. Tynjala P, Lindahl P, Honkanen V, Lahdenne P, Kotaniemi K. Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Annals of the Rheumatic Diseases 2007;66(4):548-50. - PMC - PubMed
Vastert 2014
    1. Vastert SJ, Bhat P, Goldstein DA. Pathophysiology of JIA-associated uveitis. Ocular Immunology and Inflammation 2014;22(5):414-23. - PubMed
Wallis 2005
    1. Wallis RS, Ehlers S. Tumor necrosis factor and granuloma biology: explaining the differential infection risk of etanercept and infliximab. Seminars in Arthritis and Rheumatism 2005;34(5 Suppl1):34-8. - PubMed

References to other published versions of this review

Jung 2020
    1. Jung J, Khachatryan N, Palestine A. Tumor necrosis factor (TNF) inhibitors for juvenile idiopathic arthritis‐associated uveitis. Cochrane Database of Systematic Reviews 2020, Issue 12. Art. No: CD013818. [DOI: 10.1002/14651858.CD013818] - DOI - PMC - PubMed

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