eprintid: 10204324 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/20/43/24 datestamp: 2025-02-05 09:48:08 lastmod: 2025-02-05 09:52:03 status_changed: 2025-02-05 09:48:08 type: article metadata_visibility: show sword_depositor: 699 creators_name: Acharya, Nisha R creators_name: Ramanan, Athimalaipet V creators_name: Coyne, Alison B creators_name: Dudum, Kathryn L creators_name: Rubio, Elia M creators_name: Woods, Sydney M creators_name: Guly, Catherine M creators_name: Moraitis, Elena creators_name: Petrushkin, Harry JD creators_name: Armon, Kate creators_name: Puvanachandra, Narman creators_name: Choi, Jessy T creators_name: Hawley, Daniel P creators_name: Arnold, Benjamin F creators_name: Lietman, Thomas creators_name: Porco, Travis creators_name: Von Scheven, Emily creators_name: Keenan, Jeremy creators_name: Lopez, Sarah creators_name: Gonzales, John creators_name: Ebert, Caleb creators_name: Lionetti, Geraldina creators_name: Malli, Shreya creators_name: Shantha, Jessica creators_name: Richards, Jason creators_name: Nixon, Danaye creators_name: Jackson, Kaitlyn creators_name: Doan, Thuy creators_name: Ouimette, Kevin creators_name: Zhong, Lina creators_name: Chen, Cindi creators_name: Cleary, Gavin creators_name: Gonzales-Martin, Jose creators_name: Angeles-Han, Sheila T creators_name: Utz, Virginia Miraldi creators_name: Lerman, Melissa A creators_name: Davidson, Stefanie creators_name: Stahl, Erin creators_name: Cooper, Ashley M creators_name: Dacey, Mark creators_name: Moore, Katharine F creators_name: Cooper, Jennifer C creators_name: Muthusamy, Brinda creators_name: Emami-Naeini, Parisa creators_name: Herrera Guerra, Angel Alberto creators_name: Jandial, Sharmila creators_name: Connor, Alan creators_name: Solebo, Ameenat Lola creators_name: Wedderburn, Lucy R creators_name: Ralph, Elizabeth creators_name: Sridhar, Arani creators_name: Kapoor, Bharat creators_name: Davis, Janet L creators_name: Pala, Ozlem creators_name: Renton, William D creators_name: Troutbeck, Robyn creators_name: Ashworth, Jane creators_name: Chieng, Alice creators_name: Crowell, Eric creators_name: Orrock, Janet creators_name: Vitale, Albert creators_name: Hersh, Aimee creators_name: Gangaputra, Sapna creators_name: Graham, Thomas Brent title: Stopping of adalimumab in juvenile idiopathic arthritis-associated uveitis (ADJUST): a multicentre, double-masked, randomised controlled trial ispublished: pub divisions: UCL divisions: B02 divisions: D13 divisions: G25 note: Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license, https://creativecommons.org/licenses/by/4.0/. abstract: Background: Adalimumab is an effective treatment for juvenile idiopathic arthritis-associated uveitis. Data are scarce on the effects of discontinuing adalimumab after control of the disease had been reached. We aimed to assess efficacy and safety of discontinuing treatment in patients with juvenile idiopathic arthritis-associated uveitis. // Methods: We conducted a multicentre, double-masked, randomised, placebo-controlled trial at 20 ophthalmology and rheumatology clinics across the USA, the UK, and Australia. Patients aged at least 2 years who had controlled arthritis and uveitis for at least 1 year on adalimumab were randomly assigned in a 1:1 ratio using a web-based system to receive adalimumab or placebo, administered subcutaneously every 2 weeks until the 48-week visit or treatment failure. The primary outcome was the time to treatment failure, defined by recurrence of uveitis or arthritis; all participants were included in the primary and safety analysis. Unmasking occurred at treatment failure, and patients were offered open-label adalimumab through 48 weeks of follow-up. This trial was registered with ClinicalTrials.gov (NCT03816397). // Findings: 87 patients were enrolled from March 3, 2020, to Feb 14, 2024, whereafter the prespecified interim stopping criteria were met and enrolment was stopped. One patient in each group dropped out but data were included in analyses. Six (14%) of 43 patients in the adalimumab group and 30 (68%) of 44 patients in the placebo group had treatment failure (hazard ratio 8·7, 95% CI 3·6–21·2; p<0·0001). The median time to treatment failure in the placebo group was 119 days (IQR 84–243). The median time to re-establishing sustained control of inflammation in the placebo group after restarting adalimumab was 105 days (63–196). 226 non-serious adverse events occurred in the adalimumab group (7·5 events per person-year, 95% CI 6·5–8·5), and 115 non-serious adverse events occurred in the placebo group (6·8 events per person-year, 5·6–8·1). Four serious adverse events were reported, all in the adalimumab group. // Interpretation: Discontinuing adalimumab led to higher rates of recurrence of uveitis, arthritis, or both in patients with previously controlled juvenile idiopathic arthritis-associated uveitis. However, all patients who had treatment failure successfully regained control of inflammation by the end of the 48-week study period after restarting adalimumab. // Funding: US National Institutes of Health (National Eye Institute). date: 2025-01-25 date_type: published publisher: Elsevier BV official_url: https://doi.org/10.1016/s0140-6736(24)02468-1 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2358048 doi: 10.1016/s0140-6736(24)02468-1 lyricists_name: Solebo, Ameenat lyricists_id: OASOL02 actors_name: Solebo, Ameenat actors_id: OASOL02 actors_role: owner full_text_status: public publication: The Lancet volume: 405 number: 10475 pagerange: 303-313 issn: 0140-6736 citation: Acharya, Nisha R; Ramanan, Athimalaipet V; Coyne, Alison B; Dudum, Kathryn L; Rubio, Elia M; Woods, Sydney M; Guly, Catherine M; ... Graham, Thomas Brent; + view all <#> Acharya, Nisha R; Ramanan, Athimalaipet V; Coyne, Alison B; Dudum, Kathryn L; Rubio, Elia M; Woods, Sydney M; Guly, Catherine M; Moraitis, Elena; Petrushkin, Harry JD; Armon, Kate; Puvanachandra, Narman; Choi, Jessy T; Hawley, Daniel P; Arnold, Benjamin F; Lietman, Thomas; Porco, Travis; Von Scheven, Emily; Keenan, Jeremy; Lopez, Sarah; Gonzales, John; Ebert, Caleb; Lionetti, Geraldina; Malli, Shreya; Shantha, Jessica; Richards, Jason; Nixon, Danaye; Jackson, Kaitlyn; Doan, Thuy; Ouimette, Kevin; Zhong, Lina; Chen, Cindi; Cleary, Gavin; Gonzales-Martin, Jose; Angeles-Han, Sheila T; Utz, Virginia Miraldi; Lerman, Melissa A; Davidson, Stefanie; Stahl, Erin; Cooper, Ashley M; Dacey, Mark; Moore, Katharine F; Cooper, Jennifer C; Muthusamy, Brinda; Emami-Naeini, Parisa; Herrera Guerra, Angel Alberto; Jandial, Sharmila; Connor, Alan; Solebo, Ameenat Lola; Wedderburn, Lucy R; Ralph, Elizabeth; Sridhar, Arani; Kapoor, Bharat; Davis, Janet L; Pala, Ozlem; Renton, William D; Troutbeck, Robyn; Ashworth, Jane; Chieng, Alice; Crowell, Eric; Orrock, Janet; Vitale, Albert; Hersh, Aimee; Gangaputra, Sapna; Graham, Thomas Brent; - view fewer <#> (2025) Stopping of adalimumab in juvenile idiopathic arthritis-associated uveitis (ADJUST): a multicentre, double-masked, randomised controlled trial. The Lancet , 405 (10475) pp. 303-313. 10.1016/s0140-6736(24)02468-1 <https://doi.org/10.1016/s0140-6736%2824%2902468-1>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10204324/1/ADJUST.pdf