Biologic Switching Among Nonsystemic Juvenile Idiopathic Arthritis Patients: A Cohort Study in the Childhood Arthritis and Rheumatology Research Alliance Registry

Abstract

Objective Biologic medications have significantly improved disease control and outcomes of patients with juvenile idiopathic arthritis (JIA). Current treatment recommendations suggest escalating therapy; including changing biologics if needed, when inactive or low disease activity is not attained. The patterns and reasons for switching biologics in clinical practice in North America are not well described. Methods We used the Childhood Arthritis and Rheumatology Research Alliance Registry and included individuals with JIA if they newly started a biologic after January 1, 2008 and had at least 12 months of subsequent observable time. Subjects with systemic JIA were excluded. We compared characteristics of switchers and non-switchers using chi-square for categorical variables and Wilcoxon rank sum testing for continuous variables and used linear regression for time analysis. Results 1361 eligible children with JIA in the registry started a biologic (94% tumor necrosis factor TNF inhibitors [TNFi]). Median follow-up time was 30 months, and 349 (26%) switched biologics. Among biologic switchers, ineffectiveness/disease flare was the most common reason for switch (202, 58%). The most common documented switch was from etanercept to another TNFi (221, 63%). The median time to switch to a second biologic decreased substantially from 55.2 months in 2008 to 7.2 months in 2016. Conclusion In a multicenter cohort of patients with JIA starting a biologic, one-quarter switched to a second biologic, and the time to switching decreased in recent years. Additional studies should evaluate the outcomes and optimal timing of switching and preferred sequence of biologic use.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis

“…Although tumor necrosis factor inhibitors (TNFi) are the most commonly used bDMARDs in children (32–34), other bDMARDs of proven efficacy in the treatment of JIA may be used. In the absence of head‐to‐head trials in children with oligoarthritis (35), bDMARD selection may be driven by specific provider and patient/caregiver preferences and circumstances, with the exception of interleukin‐1 (IL‐1) inhibitors, which are preferentially used for the treatment of systemic JIA (29,36–38).…”

Transition Between Treatments: What We Need to Know

“…Data on the most beneficial way to switch DMARD are still very limited. In this respect, the work of Melissa Mannion and her colleagues published in this issue of The Journal of Rheumatology is highly welcome 8 . The authors investigated the patterns and reasons for switching bDMARD in clinical practice in North America, using data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.…”

“…This suggests that pediatric rheumatologists were already practicing a steered treatment approach for JIA before the international recommendations for treating JIA to target were published. Most patients (94%) in the study by Mannion, et al had started treatment with a tumor necrosis factor inhibitor (TNFi), and the second bDMARD was also most frequently a TNFi 8 . In other countries around the world, switching to a second TNFi also seems to be the preferred choice when a first transition between bDMARD is required 9,10 .…”

“…Mannion and colleagues have not investigated whether a TNFi or non-TNFi would be more effective as a second bDMARD 8 . However, such analysis was performed in a recently published British study based on data from two UK cohort studies [the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN) and the Biologics for Children with Rheumatic Diseases (BCRD) study] 10 .…”

“…Mannion and colleagues 8 have demonstrated that cohort studies, such as the CARRA registry, are valuable in describing trends in national prescription patterns. Such disease registries can also provide effectiveness and safety data on patients beginning treatment with a medication of interest and appropriate comparator patients during the same time period.…”