Antibodies to adalimumab are associated with future inflammation in Crohn's XXXX receiving maintenance adalimumab therapy: a post hoc analysis of the Karmiris trial.

@entity1 @entity2357 @entity8787 @entity1851
INTRODUCTION: Data on immunogenicity to adalimumab (ADL) therapy in @entity1 with @entity8787 is limited. We performed additional analyses on the Karmiris cohort using the homogeneous mobility shift assay (HMSA) focusing on the inter-relationship of serum ADL concentration, antibodies-to-adalimumab (ATA), inflammatory markers and sustained response. METHODS: 536 prospectively collected serum samples were available for analysis of ADL concentration and ATA using HMSA. We studied the role of week 4 serum ADL concentration and immunomodulator (IMM) use on ATA formation with a Cox proportional hazards model. Mixed model repeated measures analysis was performed to assess the independent effects of serum ADL concentration and ATA on @entity1851 ( @entity1851 ) and response. RESULTS: ATA was detected in 20% of @entity1 after a median of 34 (12.4-60.5) weeks. ATA-positive samples correlated with lower serum ADL concentration (p<0.001). Cox regression modelling showed that week 4 ADL concentration of <5     g/mL significantly increased the future risk of ATA formation (HR=25.1; 95% CI 5.6 to 111.9; p=0.0002) and that IMM co-treatment prevented ATA formation (HR=0.23; 95% CI 0.06 to 0.86; p=0.0293). @entity2357 modelling showed a negative correlation between @entity1851 and ADL concentration (p=0.0001) and a positive one with ATA (p=0.0186). The model revealed that both lower serum ADL concentration and ATA were independently associated with future @entity1851 (p=0.0213 and p=0.0013 respectively). ATA positivity was associated with discontinuation of ADL because of loss or response (OR=3.04; 95% CI 1.039 to 9.093; p=0.034). CONCLUSIONS: ATA were detected in 20% of @entity1 . Risk of ATA formation increased with lower early serum ADL concentration and in @entity1 not on IMM. ATA and ADL were strongly associated with higher future @entity1851 level and discontinuation of ADL.
