Clinical trial NCT00902005: Endothelial Function, Inflammatory Disease Activity, and Bone and Cartilage Markers in Rheumatic Patients: The Influence of Antirheumatic Treatment
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rheumatoid Arthritis
Psoriatic Arthritis
Ankylosing Spondylitis
Endothelial Dysfunction
Inflammatory Disease Activity
Keywords: Endothelial dysfunction
Bone and cartilage markers
Inflammatory disease activity
Rheumatoid arthritis
Psoriatic arthritis
Ankylosing Spondylitis
Lead sponsor: Revmatismesykehuset AS
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2009-05-14
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline (before treatment starts), 6 weeks and 6 months after starting treatment
Secondary outcomes:
measure: CRP (C-reactive protein)
timeFrame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
measure: DAS28 (Disease activity score)
timeFrame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
measure: COMP (cartilage oligomeric matrix protein 1)
timeFrame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
measure: IL-6 (interleukin 6)
timeFrame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
measure: s-RAGE (Receptor of Advanced Glycation End products)
timeFrame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment
Other outcomes:
Locations:
city: Lillehammer
country: Norway
facility: Lillehammer Hospital for Rheumatic Diseases
state: Oppland
Study officials:
affiliation: Lillehammer Hospital for Rheumatic Diseases
name: Knut Mikkelsen, MD
role: STUDY_CHAIR
affiliation: Lillehammer Hospital for Rheumatic Diseases
name: Gunnbjørg Hjeltnes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.