@article{8cd3bd0843584884a4400f011a4bd363,
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",
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.",
keywords = "Adalimumab, Juvenile idiopathic arthritis, Randomised controlled trial, Uveitis",
author = "{the ADJUST Research Group} and Acharya, {Nisha R.} and Ebert, {Caleb D.} and Kelly, {Nicole K.} and Porco, {Travis C.} and Ramanan, {Athimalaipet V.} and Arnold, {Benjamin F.} and Acharya, {Nisha R.} and Thuy Doan and Gonzales, {John A.} and Emily von Scheven and Angeles-Han, {Shelia T.} and Virginia Miraldi Utz and Vitale, {Albert T.} and Hersh, {Aimee O.} and Overbury, {Rebecca S.} and Stahl, {Erin D.} and Cooper, {Ashley M.} and Lerman, {Melissa A.} and Davidson, {Stefanie L.} and Thorne, {Jennifer E.} and Ogbu, {Ekemini A.} and Kabita Nanda and Herlihy, {Erin P.} and Cabrera, {Michelle T.} and Dacey, {Mark S.} and Moore, {Katharine F.} and Catherine Guly and Dick, {Andrew D.} and Harry Petrushkin and Elena Moraitis and Solebo, {Ameenat L.} and Gavin Cleary and Gonzalez-Martin, {Jose A.} and Sharmila Jandial and Clarke, {Michael P.} and Kristina May and Alice Leahy and Jessy Choi and Daniel Hawley and Narman Puvanachandra and Kate Armon and Renton, {William D.} and Robyn Troutbeck",
note = "Funding Information: The trial is supported by NEI cooperative agreement UG1 EY029658 (to Dr. Nisha Acharya, primary investigator). The authors would like to thank AbbVie Pharmaceuticals for their support of the trial by donating the masked adalimumab, masked placebo, and open-label adalimumab. Funding Information: The trial is supported by NEI cooperative agreement UG1 EY029658 (to Dr. Nisha Acharya, primary investigator). The authors would like to thank AbbVie Pharmaceuticals for their support of the trial by donating the masked adalimumab, masked placebo, and open-label adalimumab. The authors would like to acknowledge the members of the DSMC: Maureen Maguire (chair), William Barlow, Jaqueline Glover, Steven Yeh, Gary Holland, and Peter Chira and the Program Official at the National Eye Institute, Donald Everett. The authors would also like to acknowledge all members of the local research teams. On behalf of the ADJUST Research Group: University of California, San Francisco: Nisha R Acharya, Travis C Porco, Benjamin F Arnold, Thuy Doan, John A Gonzales, Caleb D Ebert, and Emily von Scheven; Cincinnati Children{\textquoteright}s Hospital: Shelia T Angeles-Han and Virginia M Utz; University of Utah Health: Albert T Vitale, Aimee O Hersh, and Rebecca S Overbury; Children{\textquoteright}s Mercy Hospital: Erin D Stahl and Ashley M Cooper; Children{\textquoteright}s Hospital of Philadelphia: Melissa A Lerman and Stefanie L Davidson; The Johns Hopkins University: Jennifer E Thorne and Ekemini A Ogbu; Seattle Children{\textquoteright}s Hospital: Kabita Nanda, Erin P Herlihy, and Michelle T Cabrera; Colorado Retina Associates: Mark S Dacey; Children{\textquoteright}s Hospital Colorado: Katharine F Moore; University Hospitals Bristol and Weston: Athimalaipet V Ramanan, Catherine Guly, and Andrew D Dick; Great Ormond Street Hospital: Harry Petrushkin, Elena Moraitis, Ameenat L Solebo; Alder Hey Children{\textquoteright}s Hospital: Gavin Cleary and Jose A Gonzalez-Martin; Great North Children{\textquoteright}s Hospital: Sharmila Jandial and Michael P Clarke; University Hospitals Southampton: Kristina May and Alice Leahy; Sheffield Children{\textquoteright}s Hospital: Jessy Choi and Daniel Hawley; Norfolk and Norwich University Hospital: Narman Puvanachandra and Kate Armon; The Royal Children{\textquoteright}s Hospital: William D Renton and Robyn Troutbeck. NA is the Principal Investigator of the trial and led all stages of the trial design. NA, CE, and NK drafted the manuscript. TC and BA provided guidance on the sample size, randomisation, and statistical analysis of the trial. AR contributed to the design of the trial. All authors read and approved the final manuscript. The authors declare that they have no competing interests. The National Eye Institute, part of the National Institutes of Health, is providing funding for ADJUST, UG1 EY029658. AbbVie is providing the donation of masked study medications and open-label adalimumab for all participants. Neither the NIH nor AbbVie have any direct control on the design or conduct of the trial; the collection, analysis, or interpretation of the data; nor the writing of this manuscript. The trial protocol and informed consent documents were approved by the University of California, San Francisco Institutional Review Board (IRB #17-23987), the South Central – Berkshire Research Ethics Committee (19/SC/0112), and the Royal Children{\textquoteright}s Hospital Melbourne Human Research Ethics Committee (HREC/60373/RCHM-2020). All amendments are submitted to each country{\textquoteright}s respective ethics board. Informed consent will be collected from all participants, and the details of the consent procedures are outlined in the manuscript. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1186/s13063-020-04796-z",
language = "English (US)",
volume = "21",
journal = "Trials",
issn = "1745-6215",
publisher = "BioMed Central",
number = "1",
}