Discontinuation of systemic medications in Juvenile Idiopathic Arthritis - Risks and Remission: A Systematic Review and Meta-Analysis

OBJECTIVE: Safe and effective strategies for discontinuing systemic medications in children and adolescents with juvenile idiopathic arthritis remain to be defined. This study aimed to determine flare risks following medication discontinuation and to evaluate the impact of disease subtype, remission duration, medication class and discontinuation strategy. METHODS: A systematic review and meta-analysis (PROSPERO-CRD420251168572) was conducted using MEDLINE, EMBASE, and Web of Science evidence synthesis through October 2025. Included studies evaluated medication withdrawal-stopping versus tapering strategies in JIA patients (≤18 years) in remission. Flare was the primary outcome. Random-effects metaanalysis, subgroup analyses, meta-regression, and RoB 2 and ROBINS-I assessments were performed. RESULTS: 18 studies assessing 1,905 patients were included. Flare proportions ranged between 13%-78%, with a pooled estimate of 45% (95%CI:33%-56%;I²=97%). Lower proportions were observed with tapering, including interval spacing (25%[95%CI:8%-42%]) and dose reduction (42%[95%CI:18%-65%]) compared to stopping (57%[95%CI:44%-70%]); differences were not statistically significant. Tapering strategy was the only significant moderator of flare risk (β=0.26, p=0.02), explaining 19% of heterogeneity. Most flares occurred within 6-12 months. Flare proportions also varied by disease subtype, medication class, and remission duration before. Recapture of remission was reported in 50%-100% of patients. Incidence rate sensitivity analyses yielded consistent findings (0.35 flares/person-year). CONCLUSION: Medication discontinuation in JIA carried significant flare risk across both cumulative proportion and person-year rates. The observed heterogeneity primarily mirrored the clinical variation in withdrawal strategies. Differences in flare proportions may reflect residual drug exposure rather than the true strategy effects. The high recapture rate provides reassurance for advancing medication discontinuation approaches.