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

Phase 4

• Conditions: Rheumatoid Arthritis; Psoriatic Arthritis; Ankylosing Spondylitis; Hypertension
• Interventions: Drug: Etanercept; Drug: Adalimumab; Drug: Certolizumab; Drug: Infliximab

• Registration Number: NCT02132234
• Lead Sponsor: Jagiellonian University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2014-04-28
• Status Verified: 2014-05
• Study First Submitted QC: 2014-05-05
• Last Update Submitted: 2014-05-05
• Study First Posted: 2014-05-07
• Last Update Posted: 2014-05-07
• Primary Completion: 2014-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Biological treatment	Etanercept	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
Biological treatment	Adalimumab	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
Biological treatment	Certolizumab	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
Biological treatment	Infliximab	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

Primary Outcome Measures

Name	Time	Method
Change from baseline in blood pressure	prior to receiving anti-TNF-α treatment, 12 weeks	Ambulatory Blood Pressure Monitoring (ABPM)

Secondary Outcome Measures

Name	Time	Method
Change from baseline in endothelial function	prior to receiving anti-TNF-α treatment, 12 weeks	Flow Mediated Dilatation / Endo Pat

Trial Locations

Locations (1)

Katedra Chorób Wewnętrznych i Medycyny Wsi, Uniwersytet Jagielloński; 🇵🇱 Krakow, Skarbowa 4, Poland