Faecal Analyses in Rheumatoid Arthritis Therapy: An Prospective Observational Study of the Intestinal Microbiome in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Region Skane
- Enrollment
- 50
- Primary Endpoint
- Intestinal gut flora in rheumatoid arthritis
Study Overview
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
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.
Intervention: MTX start (Drug)
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
Intervention: TNF start (Drug)
Outcomes
Primary Outcomes
Intestinal gut flora in rheumatoid arthritis
Time Frame: Analysis made at study start/baseline
Intestinal gut flora based on DNA-based microbial analysis of fecal samples
Change in gut flora
Time Frame: 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
Time Frame: 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 Outcomes
- Adherance to immunosuppressive therapy(Analysis made at 6 months follow up)
- Change in intestinal concentration Prevotella(Change from baseline concentration at 6 months)
- Change in intestinal concentration Clostridia(Change from baseline concentration at 6 months)
- Change in intestinal concentration Lactobacillus(Change from baseline concentration at 6 months)
Investigators
Kristofer Andreasson
MD, PhD
Region Skane