Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Biologics are a main treatment option for children and young people with juvenile idiopathic arthritis (JIA) who do not respond or are intolerant to methotrexate. Unfortunately, for some children on biologics, disease control will remain elusive and they will continue to have active disease despite usage of multiple biologics; biologic refractory disease. The aim of this analysis was to quantify biologic refractory JIA and identify clinical characteristics, measured at start of first biologic, associated with biologic refractory disease.
Methods: Patients with JIA starting a first biologic, from 1st January 2010 to 31st January 2016, in two UK cohort studies were included; the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN) and the Biologics for Children with Rheumatic Diseases (BCRD) study. Data were collected at baseline, six months, one year, then annually on patient characteristics and anti-rheumatic therapy. The total number of unique biologics a patient had received was calculated. Patients were classified as refractory on the date they commenced their third biologic. Follow-up was censored at last study follow-up, 31st January 2018, or death, whichever came first. Switching patterns for biologics were described in the biologic refractory patients. Cox-regression analysis identified baseline clinical factors associated with biologic refractory disease. Multiple imputation of missing baseline data was used.
Results: There were 620 patients starting a first biologic, the majority starting tumour necrosis factor inhibitor (TNFi; 88%); 67% female, median age 11 years, median disease duration 2 years, across all ILAR categories, with a majority of patients having either polyarticular rheumatoid factor (RF) negative (32%), or extended oligoarticular JIA (20%). Overall, 39 (6.3%) patients became biologic refractory over a median of 2.9 years of follow-up; median time to third biologic was 2.5 years. The most common treatment pathways for these patients were three TNFi (26%), or two TNFi followed by either tocilizumab (28%) rituximab (12%) or abatacept (8%). The reasons given for discontinuing first and second biologic among biologic refractory patients included: 33% repeated ineffectiveness, 3% repeated adverse events, 15% ineffectiveness followed by an adverse event, 10% an adverse event followed by ineffectiveness, whilst 28% a mixture of other reasons. In the univariable analysis, patients with worse pain at the start of their first biologic were at increased risk of biologic refractory disease.
Conclusion: In this real-world cohort of children and young people with JIA, approximately 6% had received at least three different biologic therapies, here defined as biologic refractory JIA. Higher pain scores at the start of first biologic predicted refractory disease. Further understanding of why some patients are refractory to biologic therapies is vital to enable patient specific treatment pathways, accurate prognosis discussions and cost effectiveness analysis for service provisions.
To cite this abstract in AMA style:Heaf E, Kearsley-Fleet L, Davies R, De Cock D, Baildam E, Beresford MW, Foster HE, Southwood TR, Thomson W, Hyrich KL. Biologic Refractory Disease in a Cohort Study of Children and Young People with Juvenile Idiopathic Arthritis from the United Kingdom [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/biologic-refractory-disease-in-a-cohort-study-of-children-and-young-people-with-juvenile-idiopathic-arthritis-from-the-united-kingdom/. Accessed October 28, 2020.
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