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P002 Endoscopic placement of a drug-eluting platform with monoclonal antibodies in an animal model of experimental colitis by TNBS: effect on disease outcome and anti-drug antibodies (ADA’s) formation

I. Bon-Romero1,2, R. Bartolí1,2,3, N. De la Ossa4, V. Moreno de Vega2, I. Marín2, E. Domènech1,2,3, V. Lorenzo-Zúñiga1,2,3

1Health Research Institute Germans Trias i Pujol, Digestive System, Badalona, Spain, 2Germans Trias i Pujol Hospital, Endoscopy Unit, Badalona, Spain, 3CIBERehd, Madrid, Spain, 4Germans Trias i Pujol Hospital, Pathology Service, Badalona, Spain

Background

Biological treatments with monoclonal antibodies (mAb’s) are widely used in inflammatory bowel disease (IBD) in patients with a mild–severe affectation who fail to meet primary endpoints or are intolerant to conventional therapy. These drugs target pro- inflammatory cytokines or other type of molecules with an important role in IBD. mAb’s are big and complex proteins with a risk of developing an immunogenicity reaction which account for the absence or loss of response in patients through time. Our group has developed a drug-eluting platform capable of being endoscopically administered to treat locally inflammatory lesions with a lower drug dose than the systemic path. We aimed to determine the efficacy of this platform and the anti-drug antibodies (ADA) levels though the placement of our drug-eluting platform vs. submucosal injection of therapy in an experimental colitis animal model by TNBS.

Methods

Two studies were done: Acute experimental colitis (1 round of TNBS application). Five groups: Sham, Control (non-treated animals), Platform, Platform + Infliximab (1 mg/ml), Platform + Vedolizumab (1 mg/ml). Chronic experimental colitis (4 rounds of TNBS application). Two groups: Platform + Infliximab (1 mg/ml), s.c. Infliximab (5 mg/kg). Clinical and histological evaluations were done in both studies (ponderal evolution, bacterial translocation to liver, colon weight as a marker of oedema and inflammation, inflammatory cell infiltrate and intestinal architecture). ADAs levels were determined in the chronic model.

Results

On the acute model, treatment with our drug-eluting platform significantly improved clinical evaluations (ponderal evolution), macroscopic (colon weight), and histological tissue evaluations. On the chronic model, both drug-eluting platform and subcutaneous administration showed a similar fashion in resolving the disease, but the formation of ADA’s was significantly diminished with our drug-eluting platform (0.9 vs. 1.97 μg/ml-c, p = 0.0025) at day of euthanasia (Day 28).

Conclusion

Endoscopic placement of drug-eluting platforms opens a new possibility for therapeutic endoscopy. We have been able to reduce the formation of ADA’s when a biological therapy is used. This could be of great importance for the future management of patients with IBD and other pathologies where mAb’s are used.