Recurrence Risk in Pediatric Noninfectious Uveitis During Adalimumab Tapering: An International Multicenter Retrospective Study

Abstract

Objective: This study aims to assess the risk of noninfectious uveitis (NIU) relapse in pediatric patients undergoing adalimumab (ADA) tapering, evaluating potential predictors of such risk.

Methods: We conducted a multicenter retrospective cohort study involving pediatric patients with NIU who underwent ADA tapering due to inactive uveitis. Cox proportional hazards regression was used to analyze risk factors for NIU recurrence.

Results: The study cohort comprised 114 patients (65 girls; 57%). Most commonly, patients presented with juvenile idiopathic arthritis-associated uveitis (JIA-U) (52 of 114; 46%) or idiopathic uveitis (46 of 114; 40%). At ADA tapering, 46% of patients (53 of 114) experienced NIU recurrence after an overall median time of 30 weeks (interquartile range [IQR] 15-58 weeks) from the start of ADA tapering. Patients without recurrences were observed for a median of 70 weeks (IQR 48-98 weeks). Multivariate Cox regression analysis showed that a slower ADA tapering schedule was associated with a lower recurrence rate during the waning (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.21-0.74; P < 0.01). Subgroup analysis of patients with JIA-U indicated that beginning ADA tapering after at least two years of disease inactivity significantly reduced recurrence risk (HR 0.65, 95% CI 0.43-0.95; P = 0.05). Among 59 patients (52%) who discontinued ADA, recurrence rates were similar between fast- and slow-tapering groups (21% vs 33%; P = 0.6), but median time to recurrence was shorter with fast tapering (10 weeks vs 37 weeks; P = 0.05).

Conclusion: This study highlights the significant clinical impact of ADA tapering on uveitis recurrence risk, recommending a gradual, slow-tapering approach with close monitoring.

Figure 1

Kaplan‐Meier survival curves were analyzed for relapse of (A) the whole cohort, based on (B) speed class, (C) idiopathic versus JIA‐U, (D) initiating ADA tapering after at least two years of disease inactivity for the whole cohort, (E) for patients with JIA‐U, (F) and speed class restricted to patients who discontinued the drug. The long‐rank test is showed. ADA, adalimumab; DG, diagnosis; fast_t, speed classes from 5 to 10 (see Table 1); IBT, inactivity before initiation of adalimumab tapering; JIA‐U, juvenile idiopathic arthritis–associated uveitis; slow_t, speed classes from 1 to 4 (see Table 1); SPEED, class of adalimumab tapering according to the speed.

Figure 2

Multivariate Cox regression analysis assessing potential predictors of uveitis recurrence. Age: age at uveitis onset. The hazard ratio for Inactivity_BT reflects the risk associated with a 12‐week longer period of disease inactivity before tapering. fast_t, speed classes from 5 to 10 (see Table 1); Inactivity_BT, inactivity before adalimumab tapering; JIA, juvenile idiopathic arthritis; slow_t, speed classes from 1 to 4 (see Table 1); SPEED_CLASS, class of adalimumab tapering according to the speed.

Figure 3

Adalimumab dose reduction over time. Notably, 30 patients in the slow taper group and 29 in the fast‐taper group discontinued the drug. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.43165/abstract.