Methotrexate, Blood Pressure and Arterial Function in Rheumatoid Arthritis

Flinders University124 enrolled

Overview

The investigators will study the effects of methotrexate on blood pressure, arterial stiffness and endothelial function in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis have an increased risk of stroke and heart attack when compared to the rest of the population. Recent studies have shown that methotrexate, a disease-modifying antirheumatic drug (DMARDs) commonly prescribed for rheumatoid arthritis, reduces this risk. However, the mechanisms responsible for the protective effects of methotrexate on the heart and the brain are unknown. The investigators have recently completed an observational study in participants with rheumatoid arthritis treated with either methotrexate or with other DMARDs. Participants on methotrexate had lower blood pressure and 'healthier' blood vessels than participants treated with other DMARDs. These differences were maintained over a period of 8 months. These results suggest that methotrexate lowers blood pressure and exerts salutary effects on blood vessels, which might explain the reduced risk of stroke and heart attack with this drug. However, the observational nature of this study does not allow establishing a clear cause-effect relationship between methotrexate treatment and the observed changes in blood pressure and blood vessels. In order to address this issue, the investigators will recruit participants that have been recently diagnosed with rheumatoid arthritis and are about to start treatment with either methotrexate (Group 1) or another DMARD (Group 2). Then, the investigators will assess their blood pressure and blood vessels for 6 months. The investigators will use an injectable (subcutaneous) form of methotrexate because this might provide better effects on blood pressure and blood vessels. The investigators will also study a third group (Group 3) of rheumatoid arthritis participants already on treatment (\> 1 year) with oral methotrexate, with or without other DMARDs. They will be switched to subcutaneous methotrexate, but continuing all their other medications, for 6 months to see whether the subcutaneous form can further reduce blood pressure and provide additional salutary effects on blood vessels. Finally, the investigators will study a fourth group (Group 4) of participants with rheumatoid arthritis already on treatment (\> 1 year) with DMADRs other than methotrexate who will continue with the same medications for 6 months, to assess possible fluctuations in blood pressure and blood vessel markers over time. Each participant will attend three study visits (baseline, 1 and 6 months), each lasting between 60 and 90 min.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

124

Conditions

Rheumatoid Arthritis Stiffness, Aortic Endothelial Dysfunction Cardiovascular Risk Factor

Interventions

MethotrexateDRUG

See arm descriptions

SulfasalazineDRUG

See arm description

Other DMARDsDRUG

See arm

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria. * Age ≥18 years. * Written informed consent, dated and signed before initiating any study-related procedure. Exclusion Criteria: * Contraindication to MTX or sulfasalazine. * Patient who cannot be followed during 6 months. * Active alcohol or substance abuse within the last 12 months. * Participation in a clinical trial within 3 months prior to the start of the study. * Body mass index \>35 Kg/m2. * Secondary causes of hypertension. * Grade 2 (moderate) or 3 (severe) hypertension: clinic blood pressure \>160/100 mm Hg. * Resistant hypertension: clinical blood pressure ≥140/90 mm Hg despite concurrent use of three antihypertensive agents of different classes, one of which is a diuretic. * Clinical systolic blood pressure \<100 mm Hg or history of symptomatic orthostatic hypotension. * Cardiovascular event, procedure, or hospitalization for unstable angina with the last 6 months. * Atrial fibrillation. * Heart failure. * Treatment with nitrates. * Estimated glomerular filtration rate (eGFR) \<45 mL/min. * Diagnosis of polycystic kidney disease. * Glomerulonephritis treated with or likely to be treated with immunosuppressant drugs * Uncontrolled diabetes with HbA1c \>9.0% (\>75 mmol/mol). * Uncontrolled dyslipidaemia with total serum cholesterol \>7.5 mmol/L or triglycerides \>5.6 mmol/L. * Clinical diagnosis of dementia, treatment with medications for dementia or, in the opinion of the study staff, the participant is cognitively unable to follow the protocol. * Other medical, psychiatric, or behavioural factors that in the judgment of the study staff may interfere with study participation. * Cancer diagnosed and treated within the past 2 years that, in the judgment of the study staff, would compromise a participant's ability to comply with the protocol and complete the study. * Any organ transplant. * Pregnancy, currently trying to become pregnant, or of child bearing potential and not using birth control. * Significant illness within 2 weeks of study start. * Patients with an unstable active medical condition that could impair evaluation of study results.

Locations (1)

Southern Adelaide Local Health Network

Bedford Park, South Australia, Australia

Outcomes

Primary Outcomes

Change in peripheral systolic blood pressure

Time frame: Change from baseline peripheral systolic blood pressure at 6 months

Secondary Outcomes

Change in peripheral and central blood pressure

Time frame: Change from baseline peripheral and central blood pressure at 6 months

Change in arterial stiffness

Change in pulse wave velocity

Time frame: Change from baseline pulse wave velocity at 6 months

Change in arterial wave reflection

Change in augmentation index

Time frame: Change from baseline augmentation index at 6 months

Change in adenosine

Change in adenosine concentrations

Time frame: Change from baseline adenosine concentrations at 6 months

Change in arginine metabolites

Change in ADMA concentrations

Time frame: Change from baseline ADMA concentrations at 6 months

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.