Biomedicines and Bacterial Translocation in Spondyloarthritis

Bacterial Translocation in Spondyloarthritis: Evaluation Before and After Starting a Biomedicine.

The aim of this project is to evaluate the effect of anti-TNF and anti-IL17 biotherapies on bacterial translocation in patients with NSAID-resistant axial spondyloarthritis.

Axial spondyloarthritis is a common inflammatory rheumatic disease and its management is based on the use of NSAIDs and biotherapies (anti-TNF and anti-IL17 antibodies). Its pathophysiology involves the digestive mucosa. The colon of patients with spondyloarthritis is the site of asymptomatic inflammation. This inflammation results from dysbiosis, which is responsible for activation of innate immunity linked to bacterial translocation phenomena. Dendritic cells are then activated and the immune response is polarized towards the IL23/Th17 axis. This translocation is secondary to an increase in colonic permeability. The increase in digestive permeability allows translocation of bacteria or bacterial fragments, primarily lipopolysaccharide (LPS).

Some proinflammatory cytokines (TNF, IFNγ, and IL23) cause an increase in digestive permeability. IL17 produced in the digestive mucosa has two different effects. Indeed, two types of colonic T cells produce IL17: regulatory T Helpers 17 producing IL10 and IL17 and inflammatory T Helpers 17 producing IL17 and IFNγ.

The investigators hypothesize that biotherapies decrease bacterial translocation. They suspect a lesser effect of anti-IL17 compared to anti-TNF because of the potential inhibition of Treg17 lymphocytes.

Inclusion Criteria:

• Axial spondyloarthritis (2009 ASAS criteria)
• NSAID arm: Responding to any class of NSAID and not likely to initiate biotherapy
• anti-TNF/anti-IL-17 arms: Need to introduce a biomedical drug according to current recommendations (objective signs of inflammation, i.e. MRI sacroiliitis or increased CRP, and failure of two NSAIDs of different classes)

Exclusion Criteria:

• IBD already diagnosed by a gastroenterologist or suspicion of IBD (bloody diarrhea)
• Previous exposure to a biomedical drug (anti TNF or anti IL 17).
• Antibiotic use in the 3 months prior to inclusion
• Contraindications for treatment with anti-TNF or anti-IL17 (for all patients)