Adalimumab in Alleviating Inflammation in Patients With Axial Spondyloarthritis

Study Overview
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Brief Summary
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Axial spondyloarthritis is an inflammatory rheumatic disease mainly affecting joints in the spine and the sacroiliac joints. Inflammatory pathways are likely the central link from axial spondyloarthritis to the known increased risk of atherosclerotic morbidity. Positron emission tomography (PET) is the most sensitive method to detect inflammatory foci in clinical practice. A few small studies have demonstrated that PET imaging together with computed tomography (PET/CT) detects inflamed tissues in relevant patient groups. One study suggested that antirheumatic treatment diminishes the inflammation detected in PET/CT. No study so far has disclosed whether aortic inflammation is present in patients with spondyloarthritis, and whether the inflammation would wane with efficient antirheumatic treatment. The current study is aimed to grade the articular and aortic inflammatory signals in the PET/CT imaging before and after antirheumatic treatment of clinically active axial spondyloarthritis. Sixty patients aged 18-75 years with axial spondyloarthritis and radiologic sacroiliitis as detected either by MRI or X-ray will be recruited. Twenty of those are DMARD-naive, and 40 patients have axial spondyloarthritis resistant to sulfasalazine or other conventional antirheumatic drug. In addition, approximately 30 patients without spondyloarthritis but with stable coronary heart disease and approximately 20 healthy controls will be taken as historical controls. All the axial spondyloarthritis patients are PET/CT scanned after inclusion in the study. The DMARD-naive patients (n=20) are started sulfasalazine-based regimen for 12 weeks, which is the time point for a second PET scan for this subgroup. Adalimumab will be commenced for those without remission at 12 weeks. After another 16 weeks, those with adalimumab will be scanned with PET/CT for the third time. The subgroup with active disease in spite of prior conventional treatment (n=40) is also scanned with PET/CT right after the enrolment and after 16-week treatment with adalimumab. The first 15 patients form a pilot group, which is used to check the validity of the power calculation. The project will give essential new information on PET-detectable inflammation in the patients with axial spondyloarthritis. The results will be published in international publication series. The publications will form the basis for a doctoral thesis. Funding for the project comes from Abbvie Ltd.

Official Title
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The Efficacy of Adalimumab and Conventional Antirheumatic Drugs in Alleviating Axial and Aortic Inflammation Detected in PET/CT in Patients With Axial Spondyloarthritis

Conditions
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Ankylosing Spondyloarthritis

Intervention / Treatment
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* Drug: Adalimumab
* Other: PET/CT imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Axial spondyloarthritis (ASAS criteria) and radiologic sacroiliitis as detected either by MRI or X-ray. Exclusion Criteria: Psoriasis or psoriasis arthropathy Inflammatory bowel disease Unwillingness to participate in the study with additional imaging protocols Expected life-span less than <1 year Diabetes (to improve the PET imaging quality) Probable noncompliance Pregnancy Age <18 years or >75 years Contraindication for adalimumab Methotrexate used within the previous 6 months A biologic medicine used within the previous 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DMARD-naive<br>Sulfasalazine will be given as the initial therapy. | Other: PET/CT imaging<br>* PET/CT imaging<br>|
| Experimental: Post-sulfasalazine<br>Sulfasalazine contraindicated or not efficient, adalimumab will be given as the initial therapy. | Drug: Adalimumab<br>* Biologic drug<br>Other: PET/CT imaging<br>* PET/CT imaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET signals within groups | Decrease in PET signal levels both in major CV tissues (mean TBR in the whole aorta) and musculoskeletal tissues (lumbar spine and articular enthesitis as well as arthritis) after antirheumatic treatment. Thus the variables of most interest reflect intraindividual changes. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET signals between groups | Comparison of the pre-treatment PET signals between the three groups: those with axial spondyloarthritis, historical healthy controls and the patients with coronary heart disease. | 16 weeks |