Phase 4 Randomized Trial of Maintenance vs Tapered TNF‑α Inhibitor (adalimumab, etanercept, golimumab) Monotherapy in Juvenile Idiopathic Arthritis with Inactive Disease

The primary objective is to assess the effect of treatment withdrawal compared with continued stable dose of tumor necrosis factor inhibitor monotherapy on the risk of flares in children and adolescents with juvenile idiopathic arthritis who have sustained inactive disease, over a 12‑month follow‑up period. Secondary objectives include: 1) evaluation of time to flare and time to regain inactive disease during 12‑month follow‑up; 2) comparison of changes in disease activity between the treatment arms over 12 months; and 3) assessment of overall safety throughout the 12‑month period.

Participants were children and adolescents aged 2 to < 18 years who met the ILAR classification criteria for non‑systemic juvenile idiopathic arthritis and had clinically judged inactive disease for at least 12 months, documented at a minimum of two consecutive visits and confirmed by JIA‑ACR/Wallace criteria at inclusion. Both female and male patients were eligible, without active uveitis for ≥ 24 months, and were on stable tumor necrosis factor inhibitor monotherapy for ≥ 12 months prior to enrollment. Selection was based on these disease‑specific criteria; no additional lifestyle requirements such as specific diet or physical activity regimens were stipulated. The sponsor did not provide information on the total number of participants.

The Treat‑JIA trial is a phase IV, multicentre, randomized, double‑blind, controlled study evaluating maintenance versus tapered monotherapy with a TNF inhibitor in children and adolescents with juvenile idiopathic arthritis who have sustained inactive disease. After an eligibility screening visit confirming ILAR criteria, inactive disease for ≥12 months, and stable therapy for ≥12 months, participants are randomized 1:1 to continue the current dose or to undergo stepwise withdrawal. The intervention period comprises a 12‑month follow‑up with study visits at baseline (randomization), months 3, 6, 9 and 12, each assessing disease activity, adverse events, and laboratory safety; the month‑12 visit serves as the end‑of‑study assessment. Participant involvement therefore extends approximately 13–14 months including the screening visit. Early termination may occur if a disease flare meeting predefined JADAS‑27 criteria arises, if a serious adverse event or unexpected reaction is observed, if consent is withdrawn, or if protocol non‑compliance precludes continued evaluation.

The trial evaluates the impact of continued versus tapered tumor necrosis factor inhibitor monotherapy in juvenile idiopathic arthritis. Three active substances are investigated.

Golimumab is administered as Simponi 50 mg solution for injection in a pre‑filled syringe. The prescribed dose is 1.7 mg per administration, delivered by subcutaneous injection. Dosing follows the study‑specified schedule, and each injection is recorded in the participant’s dosing log.

Etanercept is supplied as either Benepali 50 mg solution for injection in a pre‑filled pen or Enbrel 25 mg solution for injection in a pre‑filled pen. Both formulations are given at a dose of 7 mg per administration by subcutaneous injection. The frequency of administration is defined by the trial protocol, and adherence is monitored through injection diaries and periodic site assessments.

Adalimumab is provided as Hyrimoz 20 mg or Hyrimoz 40 mg solution for injection in pre‑filled syringes. Each dose is 3 mg, administered subcutaneously according to the randomized dosing regimen. Compliance is tracked by electronic case report forms and patient‑reported injection records.

The primary efficacy assessment is the proportion of participants experiencing a disease flare within the first 12 months. A flare is defined as a clinically significant increase in JADAS-27 of ≥1.7 from baseline together with at least one active joint (swollen, tender, or limited range of motion) or consensus between the treating physician and the participant/parents.

Secondary efficacy measures include time to first flare, time to regain inactive disease after a flare, and longitudinal changes in validated disease‑activity scores over the 12‑month period. Safety outcomes such as adverse events, serious adverse events, and suspected unexpected adverse reactions are also recorded.

Efficacy data are collected at baseline and at scheduled study visits throughout the 12‑month follow‑up. Disease activity is quantified using the JADAS-27 score, joint counts, and physician/parent consensus. Time‑to‑event analyses are performed for flare onset and remission recovery, while the proportion of participants with flares is compared between the TNF‑α inhibitor withdrawal group and the stable‑dose group using appropriate statistical tests.