TEARE-BIO: Biomedicines and Bacterial Translocation in Spondyloarthritis
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NSAIDs Patients responding to any class of NSAIDs and unlikely to initiate biotherapy |
Other: Blood sample
Blood samples (2 times; 21mL per visit)
|
| Experimental: Anti-TNF antibody Patients requiring the introduction of biotherapy according to current recommendations and randomized to the anti-TNF treatment arm |
Other: Blood sample
Blood samples (2 times; 21mL per visit)
Drug: anti-TNF antibody administration
Anti-TNF antibody administration, according to current recommendations and randomization results
|
| Experimental: Anti-IL17 antibody Patients requiring the introduction of biotherapy according to current recommendations and randomized to the anti-IL-17 treatment arm |
Other: Blood sample
Blood samples (2 times; 21mL per visit)
Drug: anti-IL-17 antibody administration
Anti-IL-17 antibody administration, according to current recommendations and randomization results
|
Outcome Measures
Primary Outcome Measures
- Difference in serum LPS concentration [3 months]
Difference in serum LPS concentration, measured by liquid chromatography-mass spectrometry, between D0 (before anti-TNF or anti-IL 17) and D90
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre Hospitalier Universitaire de Besançon | Besançon | France | 25000 |
Sponsors and Collaborators
- Centre Hospitalier Universitaire de Besancon
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021/577