Background: Biologic therapies, second-line treatment after failure of methotrexate, have revolutionised treatment pathways and outcomes for patients with juvenile idiopathic arthritis (JIA). The expanding choice allows patients to switch biologic if current treatment is not working. Current NHS England guidelines recommend most patients with JIA to start a tumour necrosis factor inhibitor (TNFi), and if that fails switch to a second TNFi rather than change class. The evidence base for this in JIA is limited.
Objectives: The aim of this study was to compare the effectiveness of a second TNFi versus an alternative class of biologic therapy in patients with polyarticular JIA following initial TNFi therapy in routine clinical practice.
Methods: Analysis included patients with JIA starting a second biologic following initial TNFi therapy in two UK cohort studies; BSPAR-ETN and BCRD. Within the studies, data were collected at start of biologic, 6 months, 1 year, then annually on patient characteristics and anti-rheumatic therapy. Patients with extended oligoarticular and polyarticular (rheumatoid factor positive and negative) JIA were included. Patients with a history of uveitis at start of second biologic were excluded. Patient characteristics at start of second biologic were compared between patients starting a second TNFi versus an alternative class. Kaplan-Meier drug survival was used to assess drug survival on second biologic. Stop reasons of second biologic were described. Change in core outcome variables, JADAS-71, American College of Rheumatology Paediatric 50% response (ACR Pedi 50), and Minimal Clinically Important Difference (MCID; ≤0.13 reduction in CHAQ) from baseline to one year was compared between the two cohorts. Multiple imputation and propensity scores were used to account for missing baseline co-variate data and adjust for confounding by indication.
Results: 151 patients with polyarticular JIA starting a second biologic up to 13-Nov-2018 were included; 115 (76%) a second TNFi, 36 (24%) an alternative class. Patient characteristics at the start of second biologic were mostly similar except patients starting a non-TNFi had lower CRP levels (p<0.001). There was no difference in second biologic drug survival between the two cohorts of patients (p=0.8), with approximately 60% remaining on drug by one year. The majority reported inefficacy as stop reason (51%). There was no difference between one year improvement in core outcome variables or JADAS-71 after start of second biologic, and no difference in the odds of achieving ACR Pedi 50 response (odds ratio [OR] 0.8; 95% confidence interval [CI] 0.3, 2.3; p=0.7) or MCID (OR 1.0; 95% CI 0.3, 3.1; p=0.9) between patients starting a second TNFi versus a non-TNFi.
Conclusion: In this real-world cohort of children and young people with JIA starting a second biologic following initial TNFi therapy failure, there appears to be no difference between drug survival and effectiveness outcomes in those patients switching to a second TNFi compared with a non-TNFi biologic. Further research on larger sample sizes is required to know whether there is any initial advantage to switching class of drug following failure of a first TNFi.
Disclosure of Interests: Lianne Kearsley-Fleet: None declared, Rebecca Davies: None declared, Jennifer Page: None declared, Eileen Baildam: None declared, Michael Beresford: None declared, Helen Foster: None declared, Taunton Southwood: None declared, Wendy Thomson: None declared, Kimme Hyrich Grant/research support from: Grants to institution: BMS, Pfizer, UCB
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