Ten-year safety and clinical benefit from open-label etanercept treatment in children and young adults with juvenile idiopathic arthritis.
OBJECTIVES CLIPPER2 was an 8-year, open-label extension of the phase 3 b, 2-year CLIPPER study on the safety and efficacy of etanercept in patients with juvenile idiopathic arthritis (JIA), categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS Participants with eoJIA (2-17 years old), ERA, or PsA (each 12-17 years old) who received ≥1 etanercept dose (0.8 mg/kg weekly; maximum 50 mg) in CLIPPER could enter CLIPPER2. Primary end point was occurrence of malignancy. Efficacy assessments included proportions achieving JIA American College of Rheumatology (ACR) 30/50/70/90/100 criteriaand ACR inactive disease criteria, and clinical remission (ACR criteria) or Juvenile Arthritis Disease Activity Score (JADAS) ≤1. RESULTS Overall, 109/127 (86%) CLIPPER participants entered CLIPPER2 (n = 55 eoJIA, n = 31 ERA, n = 23 PsA; 99 [78%] on active treatment); 84 (66%) completed 120 months' follow-up (32 [25%] on active treatment). One malignancy (Hodgkin's disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years) was reported; there were no cases of active tuberculosis or deaths. Numbers and incidence rates [events per 100 patient-years] of TEAEs (excluding infections/ISRs) decreased from 193 [173.81] in Year 1-9 [27.15] in Year 10; TE infections and serious infections also decreased. Over 45% of participants (N = 127) achieved JIA ACR50 responses from Month 2 onwards; 42 (33%) and 17 34 (27%) participants achieved JADAS and ACR clinical remission, respectively. CONCLUSIONS Etanercept treatment up to 10 years was well tolerated, consistent with the known safety profile, with durable response in the participants still on active treatment. The benefit-risk assessment of etanercept in these JIA categories remains favorable. CLINICALTRIALS.GOV IDS CLIPPER (NCT00962741); CLIPPER2 (NCT01421069).