Anti-adalimumab antibodies are associated with active Juvenile Idiopathic Arthritis

Background/Aims Biologics have been used widely in the UK to treat Juvenile Idiopathic Arthritis (JIA) for over two decades. As this population has aged and switched biologics, there has been a growth in the cohort of patients who have switched through a greater number of biologics, consequently having fewer therapeutic options available. Our group has recently published data suggesting adalimumab has a greater drug survival compared to etanercept and infliximab. As part of our further investigation, we examined the relationship between adalimumab antibodies (AAA) and drug levels, stratified by disease activity (remission vs. active disease). Methods We conducted a retrospective observational study among patients with JIA and measured adalimumab drug levels and AAAs. The key metrics measured were AAAs (AU/L) and adalimumab drug levels (mg/mL). Disease remission was determined using standard Wallace criteria.The differences between the active and remission groups were examined with the Mann-Whitney U test. Results Among our cohort of 293 JIA patients receiving adalimumab, 179 had recorded adalimumab levels and AAAs. In 146 of these patients, we were able to measure disease activity, which was stratified into two distinct categories: Remission (N=96) and Active (N=50) according to Wallace criteria. Within our cohort of patients, there was a significant difference in both adalimumab drug levels, (P=0.004) and AAAs (P=0.00009) among those with active disease when compared to those in remission. Specifically, those with active disease exhibited a higher geometric mean AAA of 156.89AU/L [95% CIs (95% confidence intervals) 129.65-189.85] when compared to those in remission with a mean of 65.25AU/L (95% CI 41.10-103.58). The median AAA levels in those with active disease was 91AU/L (IQR 0-200), compared with 0 (IQR 0-12.5) among those in remission. With respect to adalimumab drug levels, the geometric mean in patients with active disease was 7.27mg/mL (95% CI 5.15-10.26) compared with 8.55mg/mL (95% CI 7.26, 10.07) for patients in remission. The median drug level in the active group was 2.3mg/ml (IQR 0-11.9) when compared with 9.4mg/ml (IQR 3.8-13.1) in the remission group. Conclusion Various studies have demonstrated that the presence of AAAs is associated with secondary failure in JIA and other rheumatic diseases. However, the precise relationship between AAAs, adalimumab drug concentration and disease activity are yet to be elucidated, thus their regular monitoring is not currently part of guidelines or routine clinical practice.To our knowledge this is the largest single-centered cross-sectional study investigating the relationship of AAAs and remission state in JIA.Our study demonstrates that not only are higher AAAs associated with lower drug concentration, but that this is further associated with active disease. Disclosure M.W. Carrim: None. D. Sen: None. M. Shipa: None. C. Fisher: None. T. AlSulaim: None. A. Bouraoui: None. M. Leandro: None. C. Ciurtin: None. J. Glanville: None.