Effects of Biological Treatment on Blood Pressure and Endothelial Function in Patients With Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis

Study Overview
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Brief Summary
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The aim of this study is to evaluate the influence of anti tumor necrosis factor-alpha (TNF-α) treatment on blood pressure, endothelial function and immune cell phenotype in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

Official Title
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Effects of Biological Treatment on Blood Pressure and Endothelial Function in Patients With Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis

Conditions
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Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Hypertension

Intervention / Treatment
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* Drug: Etanercept
* Drug: Adalimumab
* Drug: Certolizumab
* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For patients suffering from rheumatoid arthritis: rheumatoid arthritis diagnosed based on The American Rheumatism Association Criteria from 1987 ineffective treatment with 2 disease-modifying antirheumatic drugs (DMARDs) for 6 months each, including treatment with maximal doses of methotrexate for at least 3 months (or intolerance to treatment) high disease activity - Disease Activity Score 28 (DAS 28) > 5,1 measured twice, with a 1-month interval for patients with mainly lower limbs affected with DAS 28 > 3,7 For patients suffering from Ankylosing Spondylitis: Ankylosing Spondylitis diagnosed based on Modified New York Criteria ineffective treatment with 2 non-steroidal anti-inflammatory drugs (administered separately) in maximal recommended or maximal tolerated dose for 3 months high disease activity -Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) > 4 measured twice, with a 12-week interval spinal pain > 4cm on 10cm Visual Analogue Scale (VAS) measured twice, with a 12-week interval general disease activity assessment > 5 (0-10 scale) performed after the 2nd VAS and BASDAI assessment For patients suffering from Psoriatic Arthritis: - Psoriatic arthritis diagnosed based on the Bennett or Classification Criteria for Psoriatic Arthritis (CASPAR Criteria) If peripheral joints are affected: active disease assessed twice, with a 4-week interval on stable treatment, after 2 DMARDs treatment for at least 4 months Criteria of active disease (all have to be met): At least 5 out of 66 joints swollen - assessed twice, with a 4-week interval At least 5 out of 68 joints tender - assessed twice, with a 4-week interval general disease activity assessment of 4 or 5 in the Likert scale (0- 5 scale) performed by patient general disease activity assessment of 4 or 5 in the Likert scale (0- 5 scale) performed by physician general disease activity assessment > 5 (0-10 scale) performed after 2nd assessment of number of tender and swollen joints If axial joints are affected: Sacroiliac joints affected according to the New York Criteria of Ankylosing Spondylitis Active and severe disease assessed twice, with a 12-week interval, stable treatment, ineffective treatment with 2 nonsteroidal anti-inflammatory drugs (administered separately) in maximal recommended or maximal tolerated dose for 3 months each Criteria of active disease (all must be present): BASDAI > 4 measured twice, with a 12-week interval spinal pain > 4cm on 10 cm in the VAS measured twice, with a 12-week interval general disease activity assessment > 5 (0-10 scale) Patients can take steroid in stable dose within one month - maximal dose 10mg/day of prednisone. Exclusion Criteria: non-consenting patient pregnancy breast-feeding allergy for the drug or any component cardiac insufficiency (NYHA III or IV) active infection infection within the last 3 months: hepatitis, pneumonia, pyelonephritis opportunistic infection within the last 2 months: active infection of cytomegalovirus, Pneumocystis carinii joint infection within the last 12 months endoprosthesis infection within the last 12 months or any time if the joint was not replaced exacerbation of lung-, kidney-, liver- or heart insufficiency during treatment demyelinating disease or its symptoms pancytopenia or aplastic anemia pre-cancer stage neoplasm within the last 5 years including solid tumors and neoplasm of haematopoietic or lymphatic system with risk of recurrence or progression active alcoholic disease chronic liver disease

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biological treatment<br>Patients with high disease activity receiving biological treatment according to rheumatologic indication: etanercept 50 mg s.c. every week adalimumab 40 mg s.c. every 2 weeks certolizumab 400 mg s.c. every 2 weeks for 4 weeks, then 200mg every 2 weeks infliximab 3 or 5 mg/kg i.v. 2 and 6 weeks from the first admission, then every 8 weeks | Drug: Etanercept<br>* biological treatment according to rheumatologic indication<br>Drug: Adalimumab<br>* biological treatment according to rheumatologic indication<br>Drug: Certolizumab<br>* biological treatment according to rheumatologic indication<br>Drug: Infliximab<br>* biological treatment according to rheumatologic indication<br>|
| Placebo Comparator: control group<br>Patients with high disease activity receiving other than biological treatment and receiving placebo. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in blood pressure | Ambulatory Blood Pressure Monitoring (ABPM) | prior to receiving anti-TNF-α treatment, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in endothelial function | Flow Mediated Dilatation / Endo Pat | prior to receiving anti-TNF-α treatment, 12 weeks |