Baert, F., Kondragunta, V., Lockton, S., Vande Casteele, N., Hauenstein, S., Singh, S., Karmiris, K., Ferrante, M., Gils, A., Vermeire, S. (2016). Antibodies to adalimumab are associated with future inflammation in Crohn's patients receiving maintenance adalimumab therapy: a post hoc analysis of the Karmiris trial. Gut, 65(7), 1126-31.
INTRODUCTION:
Data on immunogenicity to (ADL) in with IBD is limited. We performed additional analyses on the cohort using the homogeneous mobility shift assay (HMSA) focusing on the inter-relationship of serum ADL concentration, -to- (ATA), inflammatory markers and sustained response.
METHODS:
536 prospectively collected serum samples were available for 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 was performed to assess the independent effects of serum ADL concentration and ATA on C-reactive protein (CRP) and response.
RESULTS:
ATA was detected in 20% of 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 µg/mL significantly increased the 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). Regression modelling showed a negative correlation between CRP 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 with CRP (p=0.0213 and p=0.0013 respectively). ATA positivity was 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 . Risk of ATA formation increased with lower early serum ADL concentration and in not on IMM. ATA and ADL were strongly with higher CRP level and discontinuation of ADL.
Bian, S., Stappen, T.V., Baert, F ., Compernolle, G., Brouwers, E., Tops, S., Vries, Ad., Rispens, T., Lammertyn, J., Vermeire, S., Gils, A. (2016). Generation and characterization of a unique panel of anti-adalimumab specific antibodies and their application in therapeutic drug monitoring assays. Journal of Pharmaceutical and Biomedical Analysis, 125, 62-7.
A number of assays are currently available to support therapeutic drug monitoring of adalimumab. A complete characterization of the assays and comparison of different assays has not been performed. The aim of this study, therefore, is to generate and characterize of a panel of monoclonal antibodies towards adalimumab (MA-ADM); to use this panel to develop novel assays to determine adalimumab concentrations; to assess the impact of tumor necrosis factor (TNF) and (non-)neutralizing antibodies on adalimumab detection and to compare the performance of assays.
In total, ten specific MA-ADM were generated of which four revealed a neutralizing potency of >78%. At least six different clusters were identified using principal component analysis. MA-ADM40D8 was selected as detecting antibody to determine adalimumab in the TNF-coated ELISA (A) and the MA-ADM28B8/MA-ADM40D8 antibody pair was chosen for use in the MA-coated ELISA (B). The impact of TNF and (non-) neutralizing antibodies was similar in both ELISAs. Finally, serum samples of adalimumab-treated Crohn’s disease patients were collected and used for an external validation using the assay of Sanquin (C) and the apDia kit (D). All adalimumab assays showed excellent Pearson correlation: r = 0.96 for A versus B, 0.96 for A versus C, 0.94 for A versus D, 0.97 for B versus C, 0.95 for B versus D and 0.94 for C and D. The excellent agreement with the two commercially available ELISAs allows harmonization of treatment algorithms in and between different hospitals/infusion centers.
De Greef, E., Hoffman, I., Smets, F., Van Biervliet, S., Bontems, P., Hauser, B., Paquot, I., Alliet, P., Arts, W., Dewit, O., De Vos, M., Baert, F., Bossuyt, P., Rahier, J.F., Franchimont, D., Vermeire, S., Fontaine, F., Louis, E., Coche, J.C., Veereman, G. (2016). Paediatric Crohn's Disease: Disease Activity and Growth in the BELCRO Cohort after 3 Years Follow-Up. Journal of Pediatric Gastroenterology and Nutrition, Jan 29.
The BELCRO cohort is a prospective, multicentre registry for newly diagnosed paediatric Crohn’s disease patients (<18yrs) recruited 2008 - 2010 to identify predictive factors for disease activity and growth.
Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow up.
At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5 % to 70%, mild 19% to 24% and moderate to severe 76% to 6%. None of the variables: age, gender, diagnostic delay, type of treatment, disease location, disease activity at diagnosis and growth were associated with disease activity at M36. Paediatricians followed significantly less patients with active disease at M36 compared to adult physicians. Sixty % of patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals ‘initiation, not disease location nor disease severity at diagnosis. Median BMI z-score evolved from -0,97 (range -5,5 to 2,1) to 0,11 (range -3,4 to 2) and median height z-score from -0,15 (range -3,4 to 1,6) to 0,12 (range -2,3 to 2,3) at M36. None of the variables mentioned above influenced growth over time.
CONCLUSIONS
Current treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or current treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36