Background/Purpose: Despite the expanding options of biologic and targeted small-molecule therapies that have improved outcomes for children with JIA, many patients continue to experience persistent disease. Difficult-to-treat rheumatoid arthritis describes patients who have persistent disease activity and difficulty with arthritis management after failing 2 or more biologic (bDMARDs) or targeted synthetic (tsDMARDs) therapies. Although there is not a similar designation in JIA, many children with arthritis suffer from refractory disease and high disease burdens. Here, we sought to characterize a cohort of treatment-refractory arthritis patients seen within our pediatric institution.

Methods: We conducted a retrospective cohort study of patients seen by pediatric rheumatology at Boston Children’s Hospital from 01/01/1998 to 07/22/2025 with ICD codes reflecting a diagnosis of JIA. Patients were included if they had confirmed arthritis and had trialed 3 or more bDMARDs or tsDMARDs classes. Data extracted included demographics, JIA subtype, associated autoimmune disorders or genetic diagnoses, number and classes of bDMARDs/tsDMARDs used, and documented reasons for medication change including efficacy, patient-described medication intolerance, drug reactions, lab abnormalities/neutralizing antibody formation, and non-adherence based on physician documentation. Number of patients who never achieved clinically inactive disease on therapy and those with concurrent use of multiple drug classes were also noted.

Results: Of 149 patients screened, 113 met inclusion criteria (excluded: no arthritis n=22; insufficient EHR data n=9; < 3 biologic failures n=5). Median age at diagnosis was 8 years (mean 8.9 ± 5.6). Most patients were female (77%). Polyarticular JIA (n=41), enthesitis-related arthritis (n=22), and psoriatic arthritis (n=29) were the most common subtypes represented. 25% of the cohort had inflammatory bowel disease or another autoimmune condition, and 16% had a reported genetic condition or VUS on genetic testing. Patients used an average of 4.5 ± 1.2 bDMARDs/tsDMARDs (range 3–8), with 32% of JIA patients having used five therapies, followed by 26% who used four. Most patients (60%) trialed three different drug classes, and 27% used four classes. Nearly all patients received conventional synthetic DMARDs (95%) and steroids (90%) while 10% patients received multiple classes of therapies concurrently. While 70% of medication switches were due to inefficacy, 12% of patients experienced medication intolerance, 21% had drug reactions, 7% had lab abnormalities and 8% had non-adherence. Notably, 21% of patients never achieved clinically inactive disease while on medications.

Conclusion: Many difficult-to-treat JIA patients have associated autoimmune diseases or genetic mutations. However, medication intolerance, drug reactions, or lab abnormalities/antibody formation to bDMARDs/tsDMARDs are also common and contribute to medication changes. Importantly, 1-in-5 never achieved clinically inactive disease, highlighting the need to better understand the factors that drive treatment-refractory arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatment-refractory-juvenile-idiopathic-arthritis-clinical-features-and-biologic-targeted-synthetic-dmard-utilization-patterns-in-a-single-center-cohort/