Rheumatoid Arthritis
Conditions
Keywords
microbiome, methotrexate, tnf-inhibitor, dysbiosis
Brief summary
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
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.
Interventions
DRUGMTX start
Patient prescribed MTX s.c. or p.o. because of active rheumatoid arthritis
DRUGTNF start
Patient prescribed TNF-inhibitor because of active rheumatoid arthritis
Sponsors
Region Skane
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intestinal gut flora in rheumatoid arthritis | Analysis made at study start/baseline | Intestinal gut flora based on DNA-based microbial analysis of fecal samples |
| Change in gut flora | Change from baseline Dysbiosis Index Score at 6 months | 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 in disease activity/treatment response at follow up | Change from baseline DAS-28 at 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adherance to immunosuppressive therapy | Analysis made at 6 months follow up | Is the patient still prescribed the same immunosuppressant compared to baseline? |
| Change in intestinal concentration Clostridia | Change from baseline concentration at 6 months | Alterations in intestinal concentrations of Clostridia bacteria according to PCR-based analysis |
| Change in intestinal concentration Prevotella | Change from baseline concentration at 6 months | Alterations in intestinal concentrations of Prevotella bacteria according to polymerase chain reaction (PCR)-based analysis |
| Change in intestinal concentration Lactobacillus | Change from baseline concentration at 6 months | Alterations in intestinal concentrations of Lactobacillus bacteria according to PCR-based analysis |
Outcome results
None listed