Biomedicines and Bacterial Translocation in Spondyloarthritis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Axial Spondyloarthritis

Intervention / Treatment
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* Other: Blood sample
* Drug: anti-TNF antibody administration
* Drug: anti-IL-17 antibody administration


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NSAIDs<br>Patients responding to any class of NSAIDs and unlikely to initiate biotherapy | Other: Blood sample<br>* Blood samples (2 times; 21mL per visit)<br>|
| Experimental: Anti-TNF antibody<br>Patients requiring the introduction of biotherapy according to current recommendations and randomized to the anti-TNF treatment arm | Other: Blood sample<br>* Blood samples (2 times; 21mL per visit)<br>Drug: anti-TNF antibody administration<br>* Anti-TNF antibody administration, according to current recommendations and randomization results<br>|
| Experimental: Anti-IL17 antibody<br>Patients requiring the introduction of biotherapy according to current recommendations and randomized to the anti-IL-17 treatment arm | Other: Blood sample<br>* Blood samples (2 times; 21mL per visit)<br>Drug: anti-IL-17 antibody administration<br>* Anti-IL-17 antibody administration, according to current recommendations and randomization results<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in serum LPS concentration | Difference in serum LPS concentration, measured by liquid chromatography-mass spectrometry, between D0 (before anti-TNF or anti-IL 17) and D90 | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bacterial translocation