RESUMO
Polyarticular juvenile idiopathic arthritis (pJIA) is a pediatric chronic inflammatory arthritis, much like rheumatoid arthritis (RA) in adults. Drug development for pJIA can potentially be expedited by using extrapolation of efficacy from adult RA; however, the lack of understanding of the response and exposure relationship between pJIA and RA to therapeutic interventions has been a major roadblock. To address this, the objective of our analysis was to conduct a systematic response and exposure comparison between pJIA and RA trials for biologic products. Data from registration RA and pJIA clinical trials (parallel or withdrawal design) for infliximab, tocilizumab, golimumab, and adalimumab were utilized. First, exposure was compared between the pJIA trials and RA pivotal trials. Subsequently, the pJIA vs. RA response similarity was assessed by comparing similar individual subcomponents of the American College of Rheumatology (ACR) scores between the two populations. The exposure comparison demonstrated that at the pJIA trial dose, exposure in pediatric patients was similar to or higher than adults for all biologics evaluated except infliximab, where lower exposure was observed in pJIA patients ≤ 35 kg. Response comparison for individual subcomponents indicated that in a majority of the cases, pJIA response was similar or higher as compared with response from RA trials. Overall, this analysis suggests response similarity between pJIA and RA across the biologic products when exposures are matched between the two populations. These analyses provide support for the use of pharmacokinetic exposure-matching for extrapolation of efficacy from adult RA to pediatric pJIA for the products with established mechanism(s) of action.