Intestinal Inflammation in Ankylosing Spondylitis and the Effects of Adalimumab on Mucosal Healing
Condition: Spondyloarthritis; Enterocolitis
MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Enterocolitis; Inflammation
Intervention: Adalimumab
Intervention description: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given
Intervention MeSH terms: Adalimumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No

Summary:

      Studies with intestinally asymptomatic patients with spondyloarthritis showed that
      approximately 1/3 had visible ulcers in the colon by scopic examinations and 2/3 had changes
      detectable by microscopy. Only those patients who improved in arthritis symptoms showed
      improvement in colonic changes. In these studies only colon and the terminal ileum was
      examined. Inflammation of the small intestine was not examined. Newer studies have shown an
      immunological link between Crohns disease and spondyloarthritis but not ulcerative colitis.
      The investigators wish to examine the small intestine in these patients before and after
      treatment, since they expect to find ulcers there linking spondyloarthritis to Crohns disease
      and healing after treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients (18 years and ≤45 years) with axial SpA according to the ASAS criteria

          -  Active SpA assessed by physician.

          -  Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.

          -  Faecal calprotectin ≥ 100mg/kg.

          -  Negative pregnancy test (serum-HCG) for women of childbearing age before the start of
             the study. (Women not of childbearing age are defined as postmenopausal for at least 1
             year or surgically sterilised (bilateral tubal ligation, bilateral oophorectomy or
             hysterectomy)). Women of childbearing age included in the study will be required to
             use contraception during the entire study period (i.e. one of the following:
             contraceptive pills, intrauterine device, depot injection of gestagen, subdermal
             implant, hormonal vaginal ring or transdermal patch). In addition, contraception must
             be used following any discontinuation of the study drug for a period of 150 days.

          -  Ability and willingness to self-administer the subcutaneous injections or have a
             person available to administer the injections.

          -  Ability and willingness to give written informed consent and meet the requirements of
             the study protocol.

        Exclusion Criteria:

          -  Diagnosed inflammatory bowel disease or high risk of intestinal stricture (previous
             abdominal stricture, radiation of abdomen, major abdominal surgery).

          -  Non steroid anti inflammatory Drugs (NSAID) ingestion less than 4 weeks before
             inclusion.

          -  Psoriasis

          -  Persons with latent Tuberculosis (TB)(positive Mantoux skin test (>10 mm), positive
             cultivation for mycobacteria in tissue samples and/or chest X-ray indicating TB) or
             other risk factors for activation of untreated latent TB.

          -  Current or recurrent infections or serious infections requiring hospitalisation or
             treatment with intravenous antibiotics within the last 30 days or oral antibiotics
             within the last 14 days before inclusion.

          -  Positive serology for Hepatitis B or C indicating active infection.

          -  Medical history of positive HIV status (in case of suspicion control of HIV test).

          -  Medical history of histoplasmosis or listeriosis.

          -  Previous cancer or lymphoid proliferative disease except completely well-treated
             cutaneous squamous cell carcinoma, basal cell carcinoma or cervical dysplasia.

          -  Previous diagnosis or signs of demyelinising diseases of the central nervous system
             (e.g. optic neuritis, disturbance of vision, disturbed gait/ataxia, facial paresis,
             apraxia).

          -  Severe renal insufficiency (creatinine clearance < 35 ml/min - normogram).Affected
             hepatic function: Liver enzymes > 3 x above the normal limit.

          -  Clinically significant drug or alcohol abuse in the last year or daily current alcohol
             consumption.

          -  Diabetes, unstable ischemic heart disease, heart failure (NYHA III-IV), recent
             apoplexia cerebri (within 3 months), chronic leg ulcer and any other condition (e.g.
             indwelling catheter) which at the discretion of the investigator means that
             participation in the protocol would entail a risk for the person in question.

          -  Anticoagulant treatment.

          -  Pregnancy or breast-feeding.

          -  Other clinically significant inflammatory rheumatologic diseases that cannot be
             related to spondyloarthritis

          -  Current parvovirus B 19 infection.

          -  Glucocorticosteroid treatment within the last 4 weeks (except nasal and inhalation
             steroids).

          -  Contraindication to study drug.