Faecal Analyses in Rheumatoid Arthritis 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 rheumatoid arthritis 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 rheumatoid arthritis coincide with specific changes in the gut flora.

Detailed Description
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Methotrexate (MTX) and tumor necrosis factor (TNF) -inhibitors are two efficient medications for the treatment of rheumatoid arthritis. 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 these medications. The purpose of this study is to understand if the gut flora may associate with treatment response. Recent studies have associated rheumatoid arthritis with intestinal dysbiosis. Specifically, the bacteria Prevotella copri, has been associated with this disease, an observation that has been supported also by mechanistic studies. In patients receiving methotrexate, normalization of dysbiosis has been associated with successful treatment. This study is of observational character and integrated in the routine clinical care of patients with rheumatoid arthritis 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. If successful treatment response in rheumatoid arthritis 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 Rheumatoid Arthritis Therapy: An Prospective Observational Study of the Intestinal Microbiome in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: MTX start
* Drug: TNF start


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rheumatoid arthritis according to the 2010 classification criteria About to start methotrexate or TNF-inhibitor because of active disease Exclusion Criteria: Failure to understand protocol A history of alcohol abuse Concomitant inflammatory bowel disease 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 |
| --- | --- |
| MTX start<br>Patients with active rheumatoid arthritis who are either naive to methotrexate, or have not used this medicine in the last year and who are about to start therapy with methotrexate i.v. or s.c. | Drug: MTX start<br>* Patient prescribed MTX s.c. or p.o. because of active rheumatoid arthritis<br>* Other names: MTX;|
| TNF start<br>Patients with active rheumatoid arthritis who are either naive to TNF-inhibitors, or have not used this medicine in the last year and who are about to start therapy with any of the following (biosimilars included); infliximab, adalimumab, etanercept, certolizumab or golimumab | Drug: TNF start<br>* Patient prescribed TNF-inhibitor because of active rheumatoid arthritis<br>* Other names: TNF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal gut flora in rheumatoid arthritis | Intestinal gut flora based on DNA-based microbial analysis of fecal samples | Analysis made at study start/baseline | 
| Change in gut flora | Change in Dysbiosis Index Score at 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. The Index has been extensively described at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029765/ | Change from baseline Dysbiosis Index Score at 6 months | 
| Change in disease activity/treatment response at follow up | Change in Disease Activity Score 28 (DAS-28), an established index of disease activity in rheumatoid arthritis between 0-10, where 10 equals maximum activity. | Change from baseline DAS-28 at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherance to immunosuppressive therapy | Is the patient still prescribed the same immunosuppressant compared to baseline? | Analysis made at 6 months follow up | 
| Change in intestinal concentration Prevotella | Alterations in intestinal concentrations of Prevotella bacteria according to polymerase chain reaction (PCR)-based analysis | Change from baseline concentration at 6 months | 
| Change in intestinal concentration Lactobacillus | Alterations in intestinal concentrations of Lactobacillus bacteria according to PCR-based analysis | Change from baseline concentration at 6 months | 
| Change in intestinal concentration Clostridia | Alterations in intestinal concentrations of Clostridia bacteria according to PCR-based analysis | Change from baseline concentration at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiome, methotrexate, tnf-inhibitor, dysbiosis