The efficacy of adalimumab and sulfasalazine in alleviating inflammation detected in PET/CT imaging in patients with axial spondyloarthritis

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2015-000752-20-FI
• Date of registration: 20/07/2015
• Prospective Registration: No
• Primary sponsor: University of Helsinki
• Public title: The efficacy of adalimumab and sulfasalazine in alleviating inflammation detected in PET/CT imaging in patients with axial spondyloarthritis
• Scientific title: The efficacy of adalimumab and conventional antirheumatic drugs in alleviating axial and aortic inflammation detected in PET/CT in patients with axial spondyloarthritis - PETSPA
• Date of first enrolment: 29/06/2015
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000752-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Finland

Contacts

• Name: Internal Medicine
• Affiliation: University of Helsinki

• Name: Internal Medicine
• Affiliation: University of Helsinki

Key inclusion & exclusion criteria

Inclusion criteria:
Sixty patients aged 18-75 years with axial spondyloarthritis and radiologic sacroiliitis as detected either by MRI or X-ray will be recruited. All the patients are required to fulfill the Assessment in SpondyloArthritis international Society (ASAS) classification criteria for radiographic axial spondyloarthritis, that is, that they have had >3 months of back pain, that they were less than 45 years at symptom onset, that they have sacroiliitis in imaging (MRI or X-ray according to modified New York criteria), and that they have one or more of the following features: dactylitis, positive family history of spondyloarthritis, inflammatory back pain, good response to NSAIDs, enthesitis, arthritis, raised CRP, HLA-B27, and uveitis.

Of the 60 patients, 20 are DMARD-naiive, and 40 patients have axial spondyloarthritis resistant to sulfasalazine or other conventional antirheumatic drug (those with methotrexate are excluded). The patients who are resistant to sulfasalazine are required to have an active disease despite sulfasalazine, determined as visual analogue scale (VAS) =4 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) =4.

An interim analysis will be made after 15 patients (pilot phase) to check the estimated parameter values used in the power calculation. Based on the number of patients typically involved in PET/CT studies, the number of patients can possibly be reduced from 60, which is the maximum number of patients to be recruited.

In addition, approximately 30 patients without spondyloarthritis but with stable coronary heart disease and approximately 20 healthy controls will be drawn from the registries of the Turku and Helsinki PET centres. The exact number of these historical controls depends on how many of them can be found from the registry. In all, the study includes 110 patients, but only 60 patients will be scanned with PET/CT within the project. The controls will be matched as well as possible using age, sex and smoking.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
• Psoriaris 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
• Contraindications for sulfasalazine or adalimumab
• Methotrexate used within the previous 6 months
• A biologic medicine used within the previous 6 months


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Axial and aortic inflammation detected in PET/CT imaging in patients with axial spondyloarthritis
MedDRA version: 18.0 Level: PT Classification code 10071400 Term: Axial spondyloarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Humira
Product Name: Humira
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Salazopyrin EN
Product Name: Salazopyrin
Pharmaceutical Form: Tablet
INN or Proposed INN: SULFASALAZINE
Other descriptive name: SULFASALAZINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: After 12 week course with sulfasalazine and 16 week course with adalimumab.

Main Objective: 1. What is the degree of disease activity or inflammation as assessed with PET/CT in symptomatic axial spondyloarthritis patients in comparison to controls? This major aim is divided to two questions based on anatomical and pathophysiological considerations:
a. Lumbar spine and articular entesitis as well as arthritis reflecting the axial spondyloarthritis per se.
b. Cardiovascular tissues, particularly thoracic aorta, reflecting the possible link between axial spondyloarthritis and atherosclerosis.

2. Does TNF-a blockade with adalimumab diminish inflammation in patients with treatment failure during conventional antirheumatic treatment?

None of these questions have been even partly covered by earlier research.

Secondary Objective: 1. How much will conventional antirheumatic treatment with sulfasalazine decrease the level of inflammation? Again, separate focus is laid on articular and cardiovascular tissues.

2. Do the changes in the level of PET/CT detected inflammation correlate with clinical rheumatologic assessment?

None of these questions have been even partly covered by earlier research.

Primary end point(s): The decrease in PET signal levels both in major cardiovascular tissues (mean target-to-background ratio in the whole aorta) and musculoskeletal tissues (lumbar spine and articular entesitis as well as arthritis) after antirheumatic treatment. Thus the variables of most interest reflect intraindividual changes.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: After 12 week course with sulfasalazine and 16 week course with adalimumab.

Secondary end point(s): Comparison of the pre-treatment PET signals between the three groups: those with axial spondyloarthritis, healthy controls and the patients with coronary heart disease.

Secondary ID(s)

PETSPA

Source(s) of Monetary Support

AbbVie Oy