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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:
The investigators want to evaluate if successful treatment of rheumatoid arthritis coincide with specific changes in the gut flora.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MTX start | 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. |
| |
| TNF start | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MTX start | Drug | Patient prescribed MTX s.c. or p.o. because of active rheumatoid arthritis |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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This study encompasses consecutive patients with rheumatoid arthritis who by their physician at the Rheumatology Clinic, Skåne University Hospital, have been prescribed any of the predefined drugs.
Patients who are willing to comply with the study protocoll are included.
The study population is consequently not a sample, but encompasses a majority of patients being prescribed theses medications at our University clinic.
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| Name | Affiliation | Role |
|---|---|---|
| Kristofer Andréasson, MD PhD | Skane University Hospital | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27894337 | Background | Andreasson K, Alrawi Z, Persson A, Jonsson G, Marsal J. Intestinal dysbiosis is common in systemic sclerosis and associated with gastrointestinal and extraintestinal features of disease. Arthritis Res Ther. 2016 Nov 29;18(1):278. doi: 10.1186/s13075-016-1182-z. | |
| 26214836 | Background | Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y, Lan Z, Chen B, Li Y, Zhong H, Xie H, Jie Z, Chen W, Tang S, Xu X, Wang X, Cai X, Liu S, Xia Y, Li J, Qiao X, Al-Aama JY, Chen H, Wang L, Wu QJ, Zhang F, Zheng W, Li Y, Zhang M, Luo G, Xue W, Xiao L, Li J, Chen W, Xu X, Yin Y, Yang H, Wang J, Kristiansen K, Liu L, Li T, Huang Q, Li Y, Wang J. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015 Aug;21(8):895-905. doi: 10.1038/nm.3914. Epub 2015 Jul 27. |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D064806 | Dysbiosis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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Faecal and blood samples from study participants are stored in a biorepository.
| TNF start | Drug | Patient prescribed TNF-inhibitor because of active rheumatoid arthritis |
|
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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 |
| 28650341 | Background | Pianta A, Arvikar SL, Strle K, Drouin EE, Wang Q, Costello CE, Steere AC. Two rheumatoid arthritis-specific autoantigens correlate microbial immunity with autoimmune responses in joints. J Clin Invest. 2017 Aug 1;127(8):2946-2956. doi: 10.1172/JCI93450. Epub 2017 Jun 26. |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |