Faecal Analyses in Spondyloarthritis Therapy

Study Overview
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Brief Summary
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This study evaluates the intestinal microbiome and disease activity in patients with spondyloarthropathies receiving immunosuppressive therapy. Patients will be analysed at two time points in reference to two predefined primary endpoints: Changes in intestinal microbiome Response to therapy The investigators want to evaluate if successful treatment of spondylarthropathy coincide with specific changes in the gut flora.

Detailed Description
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Tumor necrosis factor (TNF)-inhibition is an efficient medication for the treatment of spondyloarthropathy. In a substantial number of cases however, these medications remain ineffective. At present, the scientific community has limited understanding of why some patients are resistant to this medication. The purpose of this study is to understand if the gut flora may associate with treatment response. Spondyloarthropathies are associated with inflammatory bowel diseases in terms of epidemiology and molecular pathogenesis. Recent studies have also associated spondyloarthropathies with intestinal dysbiosis. This study is of observational character and integrated in the routine clinical care of patients with spondyloarthropathies at the Rheumatology Clinic, Skane University Hospital, Lund, Sweden. Study participants are asked to deliver blood and fecal sampling at two time-points together with clinical evaluation of disease activity. With an estimated inclusion of 50 patients, at least 20 responders and 20 non-responders are expected to be included and to be compared to each other. Our primary goal is to investigate the association between change in intestinal microbiome and clinical response to therapy. In our secondary analyses we will investigate if intestinal microbiome and intestinal inflammation at baseline may predict response to, and adherence to, therapy in these patients. If successful treatment response of spondyloarthropathy is associated with specific alterations of the gut flora, these results may guide future studies on the impact of dysbiosis and probiotics on this disease.

Official Title
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Faecal Analyses in Spondyloarthritis Therapy: A Prospective Observational Study of the Intestinal Microbiome in Patients With Spondyloarthropathy Receiving TNF-inhibition.

Conditions
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Spondyloarthropathies, Ankylosing Spondylitis

Intervention / Treatment
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* Drug: TNF-inhibition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfilling the Assessment of SpondyloArthritis International Society classification criteria for spondyloarthropathy. About to commence treatment with TNF-inhibition Exclusion Criteria: Failure to understand protocol A history of alcohol abuse Any history of diverticulitis A history of failure to comply with prescribed medication Ongoing biological therapy

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Responder<br>Patient responding to TNF-inhibition | Drug: TNF-inhibition<br>* Initiation of immunosuppression with any TNF-inhibitor, e.g. infliximab, etanercept or adalimumab<br>|
| non-Responder<br>Patient not responding to TNF-inhibition | Drug: TNF-inhibition<br>* Initiation of immunosuppression with any TNF-inhibitor, e.g. infliximab, etanercept or adalimumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gut flora | Change in Dysbiosis Index Score att follow up compared to baseline. The Dysbiosis Index Score measures degree of intestinal dysbiosis on a scale from 1 to 5, where 5 indicates dysbiosis. | Change from baseline Dysbiosis Index Score at 6 months | 
| Change in disease activity/treatment response at follow up | Change in Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), an established index of disease activity in spondylarthropathies between 0-10, where 10 equals maximum activity | Change from baseline BASDAI at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal gut flora in spondyloarthropathies | Intestinal gut flora based on DNA-based microbial analysis of fecal samples (Dysbiosis Index Score). The Dysbiosis Index Score measures degree of intestinal dysbiosis on a scale from 1 to 5, where 5 indicates dysbiosis. | Analysis made at study start /baseline | 
| Intestinal gut inflammation | Assessment of intestinal inflammation by measurement of faecal calprotectin, an established biomarker of intestinal inflammation | Analysis made at study start /baseline | 
| Adherence to immunosuppressive therapy | Is the patient still prescribed the same immunosuppressant compared to baseline? | Analysis made at 6 months follow up |