Background/Purpose: The emergence of IL-1 and IL-6 inhibitors (biologics) for the treatment of systemic juvenile idiopathic arthritis (SJIA) has dramatically improved patient outcomes. With higher proportions of patients achieving clinically inactive disease (CID), knowledge gaps exist regarding frequency and predictors of remission off of medications. We leveraged data within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry to identify demographic, clinical, and laboratory factors associated with sustained cessation (≥6 months) of glucocorticoid, biologic, and non-biologic disease modifying anti-rheumatic drugs (DMARDs) for disease remission in patients with SJIA.

Methods: 766 patients with a diagnosis of SJIA enrolled in the CARRA registry database between August 2015 – July 2020 were evaluated. Patients were excluded if they were diagnosed after enrolment, had missing diagnosis date, had change in diagnosis or unclear diagnosis, was a screen failure, if medication already discontinued prior to enrolment or administered too late after enrolment, if the diagnosis date was after medication start date, or if no exposure to pre-selected medications of interest (glucocorticoids, IL-1 inhibitor, IL-6 inhibitor, methotrexate, and/or tofacitinib). The primary outcome was medication cessation for disease remission for at least 6 month-period. Time-to-event models incorporating left truncation and right censoring with Firth correction were used to assess the association of patient demographics, SJIA disease features, baseline laboratory results, timing of medication start, and macrophage activation syndrome (MAS) with the primary outcome. Variable selection proceeded in two stages. In the first stage, univariable models were constructed. Variables that were significant at the 0.20 significance level in the univariable analysis were candidates for the multivariable model in the second stage. A backward selection approach was used to identify significant factors at the 0.05 level.

Results: A total of 493 SJIA patients met criteria for inclusion in the analysis (Table 1). Eighteen percent (90/493) of SJIA were able to wean off medications for ≥6 months. Table 2 presents the univariate relationships. In the multivariable model, younger age (HR 0.95; 95% CI 0.90-0.99; p=0.02), normal CRP levels defined as < 10 mg/L ( >=10 mg/L vs < 10 mg/L HR 0.45; 95% CI 0.26-0.78; p=0.005), and shorter time between diagnosis and start of medications (HR 0.90; 95% CI 0.82-0.995; p=0.04) were associated with successful discontinuation of medications for ≥6 months. A total of 19 (3.9%) patients developed MAS, none of whom were able to discontinue medications for ≥6 months.

Conclusion: In the CARRA SJIA cohort, being younger at enrolment, having a shorter time to start medications after diagnosis, and having a normal CRP were associated with successful medication cessation for disease remission for ≥6 month-period. This study reinforces the existing understanding of a window of opportunity in which earlier initiation of treatment for SJIA patients may lead to better outcomes.

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/patient-and-disease-level-factors-associated-with-sustained-cessation-of-medication-for-disease-remission-in-systemic-juvenile-idiopathic-arthritis/