AB1373 PREDICTORS OF RECURRENCE IN PEDIATRIC PATIENTS WITH NON-INFECTIOUS UVEITIS UNDERGOING ADALIMUMAB TAPERING: AN INTERNATIONAL MULTICENTER STUDY
Authors: A. Marino, M. V. Cicinelli, E. Miserocchi, F. Baldo, S. Costi, C. Chighizola, R. F. Caporali, F. Pichi
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Adalimumab (ADA) is frequently administered to pediatric patients with non-infectious uveitis (NIU). Given safety considerations, the quality of life of children, and cost implications, exploring the possibility of tapering/withdrawing ADA in patients experiencing a prolonged period of persistent remission has been suggested. However, few studies have investigated this in pediatric rheumatology, and none have specifically addressed how to taper/discontinue ADA in children with NIU. <h3>Objectives:</h3> To evaluate factors associated with the risk of NIU relapse in patients undergoing ADA tapering. <h3>Methods:</h3> A multicenter retrospective cohort study involving 18 international tertiary centers was conducted. Patients diagnosed with NIU, with or without an associated systemic disease, before age 18 and treated with ADA were included. ADA was administered subcutaneously every 2 weeks (20 mg for patients &lt; 30 kg; otherwise, 40 mg). All patients underwent ADA tapering due to NIU inactivity. ADA tapering consisted of progressive injection spacing decided by the treating clinician. Time-to-event analysis was used to assess the risk of NIU recurrence after ADA tapering. Patients without recurrences were censored at their last follow-up visit. Hazard ratio (HR) and 95% confidence intervals (CI) were computed. <h3>Results:</h3> The cohort comprised 114 patients (57% female) with NIU treated with ADA. Demographic and clinical characteristics of the cohort are detailed in Table 1. Fifty-three patients (46%) experienced NIU recurrence after a median of 30 weeks (IQR 15-58 weeks) from the onset of ADA tapering. A noteworthy association was identified between ethnicity and recurrence status (Table 1; p = 0.04). Asian subjects exhibited a lower susceptibility to NIU relapse compared to patients of other ethnicities (8% vs. 50%; p = 0.00). Conversely, Caucasian patients experienced more frequent relapses than non-Caucasian subjects (54% vs. 32%; p = 0.03). The interval between ADA injections was increased by 1 week every month (n =1), 1 week every 2 months (n =2), 1 week every 3 months (n = 50), 2 weeks every 4 months (n = 1), 1 week every 4 months (n = 4), 1 week every 5 months (n = 5), 4 weeks every 6 months (n = 1), 2 weeks every 6 months (n =2), 1 week every 6 months (n = 24), 1 week every 12 months (n = 24). Considering the heterogeneity in the distribution of patients across the speed of tapering, ADA tapering was classified into two main groups based on the rate of drug reduction: faster (fast_t, comprising tapering speeds from 1 week every month to 2 weeks every 4 months, N = 54) and slower (slow_t, encompassing tapering speeds from 1 week every 4 months to 1 week every 12 months, N = 60). An association between the speed class and the incidence of uveitis relapse was observed, with 56% of recurrences in the fast_t group compared to 38% in the slow_t group (p = 0.06). Univariate Cox regression analysis (Table 2) indicated that Caucasian subjects had an increased risk of uveitis recurrence compared to non-Caucasian subjects [HR 2.2; 95% CI 1.2-4.2; p = 0.01]. In contrast, Asian patients had a reduced risk (HR 0.09; 95% CI 0.01-0.07; p = 0.02). The concomitant use of MTX was associated with a high risk of uveitis relapse (HR 2.1; 95% CI 1.1-4.1; p = 0.03). Additionally, a slower taper of ADA was linked to a lower recurrence rate (HR 0.49; 95% CI 0.28-0.87; p = 0.01). A multivariate Cox regression analysis was conducted to identify independent predictors of the recurrence rate. In the multivariate model, being Caucasian remained associated with more than a two-fold increase in the risk of developing uveitis relapse (HR 2.33; 95% CI 1.12-4.85; p = 0.02). Furthermore, the adjusted analysis confirmed that a slower ADA tapering is associated with a 50% lower risk of recurrence than a faster tapering (HR 0.49; 95% CI 0.26-0.95; p = 0.03) (Table 2). <h3>Conclusion:</h3> About half of the cohort experienced a NIU relapse after the initiation of ADA tapering. Caucasian race and fast tapering were associated with a higher risk of recurrences. Therefore, a strict follow-up for these patients should be advisable, and a gradual ADA taper is recommended. <b>REFERENCES: NIL.</b> <b>Table 1.</b> General features of the cohort <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>