Comprehensive Control of Active Systemic Juvenile Idiopathic Arthritis and Long-Term Outcomes With Canakinumab Treatment

OBJECTIVES: Multi-visceral involvement and complications of systemic juvenile idiopathic arthritis (SJIA) such as macrophage activation syndrome (MAS), may strongly decrease the life expectancy and quality of life (QoL) of SJIA patients. Canakinumab is the only IL-1 inhibitor approved for SJIA by the Food and Drug Administration and the European Medicines Agency. We aimed to estimate the long-term outcomes of canakinumab utilization in previously biologic-exposed SJIA patients.

METHODS: We designed a discrete-time prediction model to estimate patterns of SJIA disease activity over time and predict life expectation and quality-adjusted life years (QALY) in the long run. Extent of disease activity was assessed with the Juvenile Arthritis Disease Activity Score (JADAS) in 27 joints using the CRP level (JADAS27‐CRP). Data on the efficacy and QoL (EQ-5D-3L) for canakinumab is from the clinical trials ß-SPECIFIC 2 (NCT00886769), ß-SPECIFIC 3 (NCT00891046), and ß-SPECIFIC 4 (NCT02296424). Time to event analysis was used to assess the occurrence of persistence on treatment with canakinumab, disease remission, disease flares, MAS and death. Country specific QoL preferences supported QALY estimation.

RESULTS: Time in remission is maximized with canakinumab treatment to 17.7 years (95%CI: 10.6-25.6). Life expectancy may be augmented by 4.1 years (95%CI: 2.0-6.5) relative to the natural history of disease. Better disease control and longer life expectancy is estimated to result in substantial QoL gains of 10.8 QALYs (95%CI: 6.3-15.5). Sequential canakinumab tapering from 4 mg/kg to 2 mg/kg every 4 weeks with further reduction from 2 mg/kg to 1 mg/kg of canakinumab every 4 weeks, and ultimately discontinuation, allows resource optimization while maintaining disease control for an extra 5 months (95%CI; 3-7).

CONCLUSIONS: Disease control with canakinumab maximizes long-term outcomes for previously biologic-exposed SJIA patients.