Long-term efficacy and safety of adalimumab for up to 6 years in patients with juvenile idiopathic arthritis

Background/Purpose: Adalimumab (ADA) has been shown safe and effective in a study of juvenile idiopathic arthritis (JIA) patients (pts) aged 4-17 years when dosed every other week for up to 3 years.1 The purpose of this report is to evaluate the long-term efficacy and safety of ADA treatment for up to 6 years in JIA pts. Methods: Pts with polyarticular course JIA were enrolled in a phase 3, randomized-withdrawal, double-blind (DB), stratified, parallel-group study, which consisted of a 16-wk open-label (OL) lead-in, a 32-wk DB phase, and an up to 5 year OL extension (OLE) phase that included BSA dosing (24 mg/m2, max 40 mg) prior to a switch to a fixed dose (FD) of 20 mg for patients weighing <=30 kg, and 40 mg for those >30 kg. Pts were required to achieve an American College of Rheumatology Pediatric 30% (ACR Pedi 30) during the OL lead-in to qualify for entry into the DB phase. Responses to ADA were evaluated based on ACR Pedi 30/50/70/90 and changes in JIA core set variables relative to baseline. Pts were monitored for adverse events (AEs). Results: Approximately 79% of patients entering the study were female, with a mean age of 11 years and a mean disease duration of 3.8 years. The mean baseline Physician's Global Assessment of disease activity (PhyGA) was 58.9, Parent's Global Assessment of overall well-being (PaGA) was 48.3,active joint count (AJC) was 17.2, and Disability Index measured by the Childhood Health Assessment Questionnaire (CHAQ) was 1.1. Among the 171 pts who enrolled in this study, 144 (84%) met ACR Pedi 30 response criteria at week 16, but 133 (78%) entered the DB phase. A total of 128 (75%) continued to the OLE (initial BSA dosing), and 106 (62%) of these pts moved on to the FD phase. Sixty-two pts completed at least 5 years in the OLE. Most pts who discontinued in the OLE were lost to follow-up or withdrew consent. The most frequent concomitant anti-rheumatic medications used during the OLE were methotrexate, non-steroidal anti-inflammatory drugs, and steroids. ACR Pedi 30/50/70/90 responses and improvements in JIA core set variables were sustained in pts who completed the study and reached ∼240 weeks in the OLE phase (Table). Of the 171 pts who received any ADA, 16 (9.4%) discontinued due to AEs. Eleven (6.4%) pts experienced serious infectious events (SIEs), and 1 (0.6%) had an opportunistic infection (cytomegalovirus). No deaths, malignancies, TB, demyelinating disease, or lupus-like reactions were reported. (Table presented) Conclusion: ADA was efficacious and well tolerated in JIA patients aged 4-17 years. Clinical responses and improvements in disease activity were maintained for up to 6 years with ADA. When compared with the 3 year study results, no new safety signals were observed through 6 years of ADA treatment.1 No malignancies or deaths were reported.