Top

Published in:

01-12-2020 | Uveitis | Study protocol

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

Authors: Nisha R. Acharya, Caleb D. Ebert, Nicole K. Kelly, Travis C. Porco, Athimalaipet V. Ramanan, Benjamin F. Arnold, the ADJUST Research Group

Published in: Trials | Issue 1/2020

Abstract

Background

Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab.

Methods

The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg).

Discussion

This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab.

Trial registration

ClinicalTrials.gov NCT03816397. Registered on 25 January 2019. EudraCT 2019-000412-29. Registered on 17 January 2019

Thierry S, Fautrel B, Lemelle I, Guillemin F. Prevalence and incidence of juvenile idiopathic arthritis: a systematic review. Jt Bone Spine. 2014;81(2):112–7 Available from: https://doi.org/10.1016/j.jbspin.2013.09.003.CrossRef

Foster CS. Diagnosis and treatment of juvenile idiopathic arthritis-associated uveitis. Curr Opin Ophthalmol. 2003;14(6):395–8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/14615646.CrossRefPubMed

Kotaniemi K, Savolainen A, Karma A, Aho K. Recent advances in uveitis of juvenile idiopathic arthritis. Sur Ophthalmol. 2003;48(5):489–502.CrossRef

Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2.PubMed

Kump LI, Castañeda RAC, Androudi SN, Reed GF, Foster CS. Visual outcomes in children with juvenile idiopathic arthritis-associated uveitis. Ophthalmology. 2006;113(10):1874–7.CrossRefPubMed

de Boer J, Wulffraat N, Rothova A. Visual loss in uveitis of childhood. Br J Ophthalmol. 2003;87(7):879–84.CrossRefPubMedPubMedCentral

Thorne JE, Woreta FA, Dunn JP, Jabs DA. Risk of cataract development among children with juvenile idiopathic arthritis-related uveitis treated with topical corticosteroids. Ophthalmology. 2010;117(7):1436–41.CrossRefPubMed

Ramanan AV, Dick AD, Jones AP, McKay A, Williamson PR, Compeyrot-Lacassagne S, et al. Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritis. N Engl J Med. 2017;376(17):1637–46 Available from: http://www.nejm.org/doi/10.1056/NEJMoa1614160.CrossRefPubMed

US Food and Drug Administration (FDA). Humira: full prescribing information [Internet]. 2018 [cited 2020 Apr 13]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125057s410lbl.pdf.

10.

National Health System. NHS England publishes clinical commissioning policy on adalimumab for children with uveitis [Internet]. 2015 [cited 2020 Apr 12]. Available from: https://www.england.nhs.uk/2015/11/adalimumab-child/.

11.

Therapeutic Goods Administration. Australian Public Assessment Report for Adalimumab [Internet]. 2017. Available from: https://www.tga.gov.au/sites/default/files/auspar-adalimumab-170320.pdf.

12.

Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies. JAMA. 2006;295(19):2275 Available from: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.295.19.2275.CrossRefPubMed

13.

Pereira R, Lago P, Faria R, Torres T. Safety of anti-TNF therapies in immune-mediated inflammatory diseases: focus on infections and malignancy. Drug Dev Res. 2015;76(8):419–27.CrossRefPubMed

14.

Baddley JW, Winthrop KL, Chen L, Liu L, Grijalva CG, Delzell E, et al. Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) study. Ann Rheum Dis. 2014;73(11):1942–8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23852763%5Cn. http://ard.bmj.com/cgi/doi/10.1136/annrheumdis-2013-203407.CrossRefPubMed

15.

Murdaca G, Spanò F, Contatore M, Guastalla A, Penza E, Magnani O, et al. Infection risk associated with anti-TNF-α agents: a review. Expert Opin Drug Saf. 2015;14(4):571–82 Available from: http://informahealthcare.com/doi/abs/10.1517/14740338.2015.1009036.CrossRefPubMed

16.

Toussi SS, Pan N, Walters HM, Walsh TJ. Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-α inhibitors: systematic review of the literature. Clin Infect Dis. 2013;57(9):1318–30 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23899685.CrossRefPubMedPubMedCentral

17.

IFHP. 2015 Comparative Price Report: variation in medical and hospital prices by country [Internet] 2015. Available from: http://www.ifhp.com/1609217/.

18.

Aquilani A, Marafon DP, Marasco E, Nicolai R, Messia V, Perfetti F, et al. Predictors of flare following etanercept withdrawal in patients with rheumatoid factor–negative juvenile idiopathic arthritis who reached remission while taking medication. J Rheumatol. 2018;45(7):956–61.CrossRefPubMed

19.

Acharya NR, Patel S, Homayounfar G, Enanoria WTA, Shakoor A, Chakrabarti A, et al. Relapse of juvenile idiopathic arthritis associated uveitis after discontinuation of Immunomodulatory therapy. Ocul Immunol Inflamm. 2019;27(4):686–92.CrossRefPubMed

20.

Shakoor A, Esterberg E, Acharya NR. Recurrence of uveitis after discontinuation of infliximab. Ocul Immunol Inflamm. 2014;22(2):96–101.CrossRefPubMed

21.

Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of health status in children with juvenile rheumatoid arthritis. Arthritis Rheum. 1994;37(12):1761–9.CrossRefPubMed

22.

Ravens-Sieberer U, Wille N, Badia X, Bonsel G, Burström K, Cavrini G, et al. Feasibility, reliability, and validity of the EQ-5D-Y: results from a multinational study. Qual Life Res. 2010;19(6):887–97 Available from: https://doi.org/10.1007/s11136-010-9649-x.CrossRefPubMedPubMedCentral

23.

Felius J, Stager DR, Berry PM, Fawcett SL, Stager DR, Salomão SR, et al. Development of an instrument to assess vision-related quality of life in young children. Am J Ophthalmol. 2004;138(3):362–72.CrossRefPubMed

24.

Angeles-Han ST, Griffin KW, Harrison MJ, Lehman TJA, Leong T, Robb RR, et al. Development of a vision-related quality of life instrument for children ages 8-18 years for use in juvenile idiopathic arthritis-associated uveitis. Arthritis Care Res. 2011;63(9):1254–61.CrossRef

25.

Consolaro A, Ruperto N, Bazso A, Pistorio A, Magni-Manzoni S, Filocamo G, et al. Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum. 2009;61(5):658–66 Available from: http://doi.wiley.com/10.1002/art.24516.CrossRefPubMed

26.

Friedman LM, Furberg CD, DeMets DL. Fundamentals of clinical trials [internet]. New York: Springer; 2010. Available from: https://books.google.com/books?id=pIx-0LvD6agC.CrossRef

27.

Castiblanco C, Meese H, Foster CS. Treatment of pediatric uveitis with adalimumab: the MERSI experience. J AAPOS. 2016;20(2):145–7.CrossRefPubMed

28.

R Core Team. R: a language and environment for statistical computing [Internet]. 2013. Available from: http://www.r-project.org/.

29.

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.CrossRefPubMed

30.

Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208 Available from: http://www.sciencedirect.com/science/article/pii/S1532046419301261.CrossRefPubMedPubMedCentral

31.

US Food and Drug Administration (FDA). IND application reporting: safety reports [Internet]. 2015. Available from: https://www.fda.gov/drugs/investigational-new-drug-ind-application/ind-application-reporting-safety-reports.

32.

World Health Organization. The use of the WHO–UMC system for standardised case causality assessment. [cited 2020 Apr 13]. Available from: https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf.

33.

Chang CY, Meyer RML, Reiff AO. Impact of medication withdrawal method on flare-free survival in patients with juvenile idiopathic arthritis on combination therapy. Arthritis Care Res (Hoboken). 2015;67(5):658–66.CrossRef

34.

Casanova MJ, Chaparro M, García-Sánchez V, Nantes O, Leo E, Rojas-Feria M, et al. Evolution after anti-TNF discontinuation in patients with inflammatory bowel disease: a multicenter long-term follow-up study. Am J Gastroenterol. 2016;112(October 2016):120–31.PubMed

Title: 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
Authors: Nisha R. Acharya
Caleb D. Ebert
Nicole K. Kelly
Travis C. Porco
Athimalaipet V. Ramanan
Benjamin F. Arnold
the ADJUST Research Group
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Uveitis
Adalimumab
Juvenile Rheumatoid Arthritis
Juvenile Rheumatoid Arthritis
Published in: Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-020-04796-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2020

A mobile app using therapeutic exercise and education for self-management in patients with hand rheumatoid arthritis: a randomized controlled trial protocol

Exclusion rates in randomized controlled trials of treatments for physical conditions: a systematic review

Should the nail plate be replaced or discarded after nail bed repair in children? Nail bed INJury Analysis (NINJA) randomised controlled trial: a health economic and statistical analysis plan

Elbow hemiarthroplasty versus open reduction and internal fixation for AO/OTA type 13 C2 and C3 fractures of distal humerus in patients aged 50 years or above: a randomized controlled trial

Effectiveness of using a meditation app in reducing anxiety and improving well-being during the COVID-19 pandemic: A structured summary of a study protocol for a randomized controlled trial

Delivery of a Mental Health First Aid training package and staff peer support service in secondary schools: a process evaluation of uptake and fidelity of the WISE intervention