Faecal Analyses in Spondyloarthritis Therapy (FAST)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Ankylosing Spondylitis; Spondyloarthropathies
• Intervention / Treatment: Drug: TNF-inhibition

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Kristofer Andréasson, MD PhD; Phone Number: +4646172153; Email: kristofer.andreasson@med.lu.se
• Study Contact Backup: Name: Johan Karlsson Wallman, MD PhD; Phone Number: +4646172140; Email: johan.81.karlsson@gmail.com

Study Locations

• Sweden
  • Lund, Sweden, 221 85
    • Recruiting
    • Reumatologi SUS Lund, Region Skåne
    • Contact: Kristofer Andréasson, MD PhD; Phone Number: +4646171000; Email: kristofer.andreasson@med.lu.se
    • Contact: Johan Karlsson Wallman, MD PhD; Phone Number: +4646171000; Email: johan.81.karlsson@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study encompasses consecutive patients with spondyloarthropathy who by their physician at the Rheumatology Clinic, Skåne University Hospital, have been prescribed a TNF-inhibitor.

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 spondyloarthropathy patients being prescribed this medication at our University clinic.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Responder; Patient responding to TNF-inhibition	Drug: TNF-inhibition; Initiation of immunosuppression with any TNF-inhibitor, e.g. infliximab, etanercept or adalimumab
non-Responder; Patient not responding to TNF-inhibition	Drug: TNF-inhibition; Initiation of immunosuppression with any TNF-inhibitor, e.g. infliximab, etanercept or adalimumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Region Skane
• Investigators: Principal Investigator: Kristofer Andréasson, MD PhD, Lund University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; Ankylosis; Axial Spondyloarthritis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Spondylarthropathies
• Other Study ID Numbers: FAST1 (Shire HGT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No