Pos0777 adalimumab and Anti-Drug Antibodies in a Cohort of Children With Juvenile Idiopathic Arthritis: A Single-Center Experience

Abstract

BackgroundAdalimumab (ADA), a fully humanized antibody against tumor necrosis factor (TNF)-α, has revolutionized treatment of patients with juvenile idiopathic arthritis (JIA). Although most of these respond within the first weeks, a minority may show loss of response (LOR) after continued exposure. Many studies demonstrate the influence of anti-adalimumab antibodies (AAA) on serum drug concentrations and clinical outcome in adults. However, little information about AAA and LOR is available for children with JIA.ObjectivesTo describe demographic and clinical features in a single-center cohort of JIA patients treated with ADA, grouped according to frequency of drug administration (1W vs 2W); to assess ADA levels versus AAA titer and, finally, to investigate possible correlation between LOR to ADA and AAA.MethodsRecords of JIA patients on ADA treatment were retrospectively reviewed with focus on medical history and ELISA (enzyme-linked immunosorbent assay) ADA/AAA levels in a 12-month-period (Feb 2021-Feb 2022). Children with idiopathic uveitis were excluded. Samples furthest from last drug administration was defined as “trough level”. Data were analyzed via descriptive statistics (STATA 15.1).ResultsOf 61 JIA patients treated with ADA (49% females), 38 had ANA positive oligoarthritis with almost one large joint involvement at disease onset (T0). None of them presented RF-positive polyarthritis, nor systemic JIA (s-JIA). The median age at T0 was about 3 years. Half of study cohort was b-DMARDS naive at ADA start (T1), while all children were on c-DMARDs. Chronic recurrent uveitis was the main reason for ADA starting, followed-by tenosynovitis and spine or hip active arthritis. At the first ADA/AAA sampling (T2), approximately 15% of patients had active disease, with elbows or wrists as the most frequently involved. Extreme variability was observed between AAA titers (median 7.4 AU/ml) and ADA levels (median 15.4 micrograms/ml), regardless from 1 or 2-weekly administration. ADA levels, compared to the days from last drug administration, reached plateau values corresponding to a pharmacokinetic steady state. Among both study groups, a possible inverse correlation between ADA and AAA was found. We identified 30 JIA patients with clinical (presence of arthritis or uveitis) or laboratory (ESR ≥15 mm/h; CRP> 0.5 mg/dL) disease activity. Among these in only 6 we found very high AAA titers (350.0 - 113.4 AU/mL). In the subgroup of 37 patients with “trough-level” sampling heterogeneous data about AAA titers and drug level distribution were observed.ConclusionOur preliminary data showed a possible association between occurrence of AAA and lower ADA levels. However, a targeted risk analysis about high AAA titers and LOR incidence was not available. Monitoring of drug immunogenicity should be implemented in daily practice and become subject of future studies JIA.References[1]Brunelli et al. “Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switvhing” Clin Rheumatol 2019[2]Skrabl-Baumgartner A. et al. “Anti-adalimumab antibodies in juvenile idiopathic arthritis: frequent association with loss of response”. Scand J Rheumatol 2015[3]Imagawa T. et al. “Anti-adalimumab antibodies in a cohort of patients with juvenile idiopathic arthritis: incidence and clinical correlations”. Clin Rheumatol 2018Acknowledgements:NIL.Disclosure of InterestsNone Declared.