In addition to demonstrating efficacy, the numbers and incidence rates of treatment-emergent adverse events and treatment-emergent infections decreased throughout the 10-year follow-up.
Treatment with etanercept was well tolerated for up to 10 years in patients with juvenile idiopathic arthritis (JIA), according to data published in Rheumatology.1 Results were consistent with the known safety profile and demonstrated durable response in patients receiving the drug, making it a favorable option for this patient population.
Etanercept, a tumor necrosis factor α inhibitor (TNFα), has previously been proven to be effective and well-tolerated in patients with polyarticular JIA, and demonstrated durable responses and an acceptable safety profile during an 8-year open-label extension follow-up period.2
“Despite substantial progress in the treatment of JIA over recent years, JIA remains a chronic condition for many affected children, and a significant portion of patients require treatment into adulthood, wrote Jelena Vojinović, MD, PhD, Department of Pediatric Immunology and Rheumatology, University of Niš, Serbia, and a team of international investigators. “It is important to understand the long-term safety and clinical benefit profile when treating young patients with biologics.”
In the 8-year, open-label CLIPPER2 trial, an extension of the phase 3b, 2-year CLIPPER study, investigators analyzed the safety and efficacy of etanercept in patients with JIA, who were categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). Patients aged 2-17 years with eoJIA or aged 12-17 years with ERA or PsA who received ≥1 dose of etanercept (.8 mg/kg weekly; maximum 50 mg) in the CLIPPER trial were eligible to enter CLIPPER2.
The primary endpoint was incidence of malignancy. Efficacy measurements included the American College of Rheumatology (ACR) inactive disease criteria and achievement of JIA ACR 30/50/70/90/100 improvement response, as well as clinical remission (ACR criteria) or Juvenile Arthritis Disease Activity Score (JADAS) ≤1.
Most (86%, n = 109/127) CLIPPER patients entered CLIPPER2, of which 55 had eoJIA, 31 had ERA, and 23 had PsA. Most (78%, n = 99) were currently on active treatment, 66% (n = 84) completed 120 months of follow up with 25% (n = 32) of that group on active treatment.
During the trial, 1 malignancy was reported (Hodgkin’s disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years); however, there were no deaths or cases of active tuberculosis.
The numbers and incidence rates of treatment-emergent adverse events (TEAEs), excluding infections and injection site reactions, decreased from 193 in year 1 to 9 in year 10. The most common AEs were headache, diarrhea, arthralgia, pyrexia, leukopenia. The treatment-emergent infections and serious infections also decreased during this time, with the most common reported as upper respiratory tract infections. Most treatment-emergent infections were categorized as mild or moderate severity.
Almost half (45%, n = 127) of patients achieved JIA ACR50 by month 2, 33% (n = 42) achieved JADAS, and 27% (n = 34) achieved ACR clinical remission.
Investigators noted that the study duration strengthened the data by providing efficacy and safety assessments over a long period of time. However, they reported that the lack of a control group and the non-randomized, open-label design may have hindered results. Further, a large proportion of patients had missing data or discontinued treatment during the 10-year period. Therefore, the low participant numbers at later time points indicate that findings should be interpreted cautiously.
“The safety profile of etanercept during the 10 years of total follow-up was similar to that in previous JIA studies and consistent with the known safety profile of etanercept,” investigators concluded.