Endothelial Function, Inflammatory Disease Activity, and Bone and Cartilage Markers in Rheumatic Patients: The Influence of Antirheumatic Treatment (PSARA)

Endothelial Function, Inflammatory Disease Activity, and Bone and Cartilage Markers in RA and Spondyloarthritis Patients, Treated With TNFalpha-inhibitors in Combination With Methotrexate or Methotrexate or TNFalpha-inhibitors Alone - a Prospective Study

The aim of this study is to examine the associations between inflammatory disease activity and endothelial function in rheumatoid arthritis (RA) and spondyloarthritis patients treated with methotrexate and Tumor Necrosis Factor alpha (TNFalpha)inhibitor in combination or methotrexate or TNFalpha-inhibitor alone. Further, to look for improvement in endothelial function, and decrease in bone and cartilage destruction during treatment with the combination therapy of TNFalpha-inhibitor and methotrexate in RA and Psoriatic Arthritis (PSA) patients. Last, examine the TNFalpha inhibitors influence on endothelial function and levels of bone and cartilage markers in patients with Ankylosing Spondylitis (AS).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Endothelial Dysfunction; Psoriatic Arthritis; Ankylosing Spondylitis; Inflammatory Disease Activity

• Study Type: Observational
• Enrollment (Actual): 145

Contacts and Locations

Study Locations

• Norway
  • Oppland
    • Lillehammer, Oppland, Norway, 2609
      • Lillehammer Hospital for Rheumatic Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with RA and spondyloarthritis starting with either combination therapy of TNFalpha-inhibitor and methotrexate or methotrexate or TNFalpha-inhibitor alone, at Lillehammer Hospital for Rheumatic diseases.Decision about treatment modality will be based on conventional clinial judgement.

Description

Inclusion Criteria:

• Males and females 18-80 years
• Able and willing to give written informed consent, and to comply with the requirements of the study protocol.
• Fulfilling the ACR 1987 revised diagnostic criteria for the diagnosis rheumatoid arthritis, or the diagnostic criteria by Moll and Wright for the diagnosis psoriatic arthritis, or the modified New York diagnostic criteria for ankylosing spondylitis.
• Clinical indication for starting treatment with methotrexate, TNFalpha- inhibitor or combination therapy.
• Use of reliable method of contraception for women with childbearing potential.

Exclusion Criteria:

• Lack of cooperativity
• Positive serology for hepatitis B or C
• History of positive HIV status.
• History of tuberculosis or untreated tuberculosis.
• PPD more than 15 mm in previously BCG immunized subjects. PPD 6 mm or more if not previously BCG immunized.
• Histoplasmosis or Listeriosis
• Persistent or recurrent infections
• Any inflammatory disease of permanence not related to RA, PSA or AS.
• Pregnancy or breast-feeding.
• Use of prednisolone more than 10 mg daily for 2 weeks at inclusion.
• Use of TNFalpha-inhibitor the last 4 weeks.
• History of cancer.
• Uncontrolled diabetes.
• Congestive heart failure (Nyha 3-4)
• Recent stroke (within 3 months)
• Previous diagnosis or signs of central nervous system demyelinating disease.
• Previously diagnosed immunodeficiency.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Rheumatic patients; Three groups: RA patients: 30 starting on Methotrexate, 30 starting on combination of Methotrexate and TNFalpha inhibitor. PSA patients: 20 starting on Methotrexate, 20 starting on combination of Methotrexate and TNFalpha inhibitor. AS patients: 20 starting on TNFalpha inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To examine the association between inflammatory disease activity and endothelial function in RA and spondyloarthritis patients treated with methotrexate and TNFalpha-inhibitor in combination or methotrexate or TNFalpha-inhibitor alone	Baseline (before treatment starts), 6 weeks and 6 months after starting treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
CRP (C-reactive protein)	Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
DAS28 (Disease activity score)	Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
COMP (cartilage oligomeric matrix protein 1)	Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
IL-6 (interleukin 6)	Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
s-RAGE (Receptor of Advanced Glycation End products)	Baseline (before starting treatment), 6 weeks, 6 months after starting treatment

Collaborators and Investigators

• Sponsor: Revmatismesykehuset AS
• Collaborators: Abbott
• Investigators: Study Chair: Knut Mikkelsen, MD, Lillehammer Hospital for Rheumatic Diseases; Principal Investigator: Gunnbjørg Hjeltnes, MD, Lillehammer Hospital for Rheumatic Diseases

Publications and helpful links

General Publications

• Hokstad I, Deyab G, Wang Fagerland M, Lyberg T, Hjeltnes G, Forre O, Agewall S, Mollnes TE, Hollan I. Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study. PLoS One. 2019 Jul 23;14(7):e0220079. doi: 10.1371/journal.pone.0220079. eCollection 2019.
• Deyab G, Hokstad I, Whist JE, Smastuen MC, Agewall S, Lyberg T, Ronda N, Mikkelsen K, Hjeltnes G, Hollan I. Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis. Arthritis Res Ther. 2017 Oct 17;19(1):232. doi: 10.1186/s13075-017-1439-1.
• Ronda N, Greco D, Adorni MP, Zimetti F, Favari E, Hjeltnes G, Mikkelsen K, Borghi MO, Favalli EG, Gatti R, Hollan I, Meroni PL, Bernini F. Newly identified antiatherosclerotic activity of methotrexate and adalimumab: complementary effects on lipoprotein function and macrophage cholesterol metabolism. Arthritis Rheumatol. 2015 May;67(5):1155-64. doi: 10.1002/art.39039.
• Hjeltnes G, Hollan I, Forre O, Wiik A, Lyberg T, Mikkelsen K, Agewall S. Relations of serum COMP to cardiovascular risk factors and endothelial function in patients with rheumatoid arthritis treated with methotrexate and TNF-alpha inhibitors. J Rheumatol. 2012 Jul;39(7):1341-7. doi: 10.3899/jrheum.111401. Epub 2012 Jun 1.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: May 13, 2009
• First Submitted That Met QC Criteria: May 13, 2009
• First Posted (Estimate): May 14, 2009

Study Record Updates

• Last Update Posted (Estimate): November 21, 2013
• Last Update Submitted That Met QC Criteria: November 20, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Endothelial dysfunction; Psoriatic arthritis; Rheumatoid arthritis; Ankylosing Spondylitis; Bone and cartilage markers; Inflammatory disease activity
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Psoriasis; Bone Diseases, Infectious; Ankylosis; Arthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
• Other Study ID Numbers: S-07377b