The Efficacy of Fecal Microbiota Transplatation on Axial Spondyloarthritis Patients Resistant to Conventional Treatment

Axial spondyloarthritis (SpA) is a chronic inflammatory disease primarily affecting the sacroiliac and spinal joints that usually begins in young adults and is a major cause of chronic pain and disability that profoundly alter the quality of life of patients. Besides non-steroidal anti-inflammatory drugs, the development of anti-tumor necrosis factor-α (TNFα) and anti-interleukin (IL-17) biotherapies and of JAK inhibitors, has improved the management of these patients. However only half of the patients respond to these treatments and many of them are only partially relieved. Remarkably, this disorder frequently combines with overt inflammatory bowel disease (IBD) -i.e. Crohn's disease (CD) or ulcerative colitis (UC)- and even more frequently with subclinical gut inflammation, leading to suspect a role of the gut microbiota as a possible trigger. Consistently, recent studies evidenced an alteration of gut microbiota composition -or dysbiosis- in the course of SpA that appeared all the more pronounced that disease was more active. It was notably shown a restriction of bacterial diversity and an expansion of species considered as potentially pro-inflammatory, including Ruminococcus gnavus. Given its potential involvement in the pathogenesis of SpA, gut microbiota could be considéred as a promising therapeutic target. Fecal microbiota transplantation (FMT) is a technic consisting in thorough replacement of dysbiotic microbiota by healthy dondor's microbiota that has recently been developped to correct dysbiosis. It has been validated for the treatment of intractable colitis due to Clostridium difficile and its efficacy has been reported in CD or UC. The current trial, aims to evaluate efficacy of FMT in drug-resistant axial SpA.

Inclusion criteria

• Adult patient (age 18 to 75 years old) with SpA, meeting the ASAS classification criteria for axial SpA, with presence of radiographic sacro-illitis (ankylosing spondylitis) or not.
• Patient suffering of active SpA, with or without treatment, having a BASDAI score ≥ 4 (0-10) at baseline and a score of back pain ≥ 4 (0-10) despite optimal drug management for at least 6 months including at least 2 different NSAIDs at the maximum tolerated dose for at least 2 months (or less in case of intolerance or contra-indication) and at least a first line of biotherapy (anti-TNFα or anti-IL-17) for at least 4 months (or less in case of intolerance or contra-indication).
• Subjects are allowed to continue NSAID, sulfasalazin (≤ 3 g/day) and/or methotrextae ( ≤ 25 mg/week) and/or hydroxychloroquine (≤ 400 mg/day) and/or oral corticosteroid (≤ 10 mg/day of prednisone), as long as these treatments have remained at stable dose for 4 weeks prior to baseline.
• Subjects are allowed to continue anti-TNFα, anti-IL-17 or JAKinhibitor therapies, as long as these treatments have remained at stable dose for 3 months prior to baseline.
• Women of childbearing potential with efficient contraceptive protection at the inclusion and during at least the interventional phase (D168).
• Patient with health insurance (AME except).
• Patient is willing to provide written informed consent prior to enrolment and agrees to follow the protocol.

Exclusion criteria

• Patient under legal protection (guardianship or curatorship)
• Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development
• Pregnant or breastfeeding woman
• Patient with IBD in active state, according to the judgment of the Investigator
• Corticosteroid injection within 4 weeks before inclusion
• Active infection according to the judgment of the Investigator
• Any antibiotic (including Sulfasalazin) or antifungal treatment within 4 weeks before inclusion
• Probiotics intake within 4 weeks before inclusion
• Known infection with Clostridoides difficile or Escherichia coli within 10 days before inclusion
• Patients with unstable severe condition other than axial SpA on that could jeopardize treatment procedure or evaluation according to the investigator's assessment
• Previous FMT treatment
• Contra-indication to colon preparation (Moviprep® or Moviprep orange®) according to SmPC
• Current or past evidence of bowel obstruction
• Confirmed or suspected intestinal ischemia
• Confirmed or suspected toxic megacolon or gastrointestinal perforation
• Extended colectomy (> two-thirds of colon)
• Any gastro-intestinal bleeding in the past 3 months before inclusion
• Any history of gastro-intestinal surgery in the past 3 months before inclusion
• Severe organ dysfunction
• Any contra-indication to swallow capsules
• Known allergy or intolerance to IMP and / or excipients according to Investigator's Brochure
• Lack of access to a refrigerator to store the medication (MaaT033® or MaaT030®)
• Concomitant participation in another interventional clinical trial