Purpose

In a randomized controlled clinical trial, investigators will compare the effects on [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) from two treatment regimens in rheumatoid arthritis (RA) patients deemed methotrexate inadequate responders (MTX-IRs). Two common RA treatments will be compared: triple therapy (sulfasalazine, methotrexate, and hydroxychloroquine) versus tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening).

Condition

Eligibility

Eligible Ages
Over 45 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Fulfill American College of Rheumatology/European League Against Rheumatism 2010 criteria for RA
  • Men ≥ 45 years and women ≥ 50 years
  • MTX monotherapy for ≥ 8 weeks at ≥ 15mg weekly or ≥ 7.5 mg weekly with a documented intolerance to higher doses
  • No non-biologic DMARDs in preceding two months (other than MTX and HCQ)
  • Disease Activity Score-28 > 3.2
  • Able to sign informed consent

Exclusion Criteria

  • Use of biologic DMARD within the past 6 months or use of rituximab ever
  • Current use of >10mg per day of prednisone
  • Use of a high-intensity statin lipid lowering drug or PCSK9 inhibitor in the past 12 months
  • Prior patient reported, physician diagnosed clinical cardiovascular (CV) event
  • Insulin-dependent or uncontrolled diabetes mellitus (DM)
  • Systemic lupus erythematosus (SLE) or other autoimmune and chronic inflammatory diseases (i.e. inflammatory bowel disease, sarcoidosis)
  • Cancer treated in the last 5 years (except basal and squamous cell) or any lymphoma or melanoma
  • Known pregnancy, HIV, Hepatitis B Virus, Hepatitis C Virus, active (or untreated latent) tuberculosis
  • Baseline: liver, renal or blood count abnormalities, Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Known sulfa allergy, macular disease or hypersensitivity to treatments; known demyelinating disease; uncompensated Congestive Heart Failure (CHF)
  • Intra-articular injection within the 4 weeks prior to baseline FDG PET/CT
  • 2 or more high dose radiation scans in the past year (CT scan with contrast, angiogram, SPECT nuclear medicine scan, myocardial/cardiac perfusion scan)

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Triple therapy (MTX+SSZ+HCQ)
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate [MTX]).
  • Drug: Methotrexate
    Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
    Other names:
    • Rheumatrex
  • Drug: Sulfasalazine
    1 gm bid
    Other names:
    • Azulfidine
  • Drug: Hydroxychloroquine
    200 mg twice daily, not to exceed 6.5mg/kg
    Other names:
    • Plaquenil
Active Comparator
TNF inhibitor (etanercept or adalimumab)
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
  • Drug: Methotrexate
    Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
    Other names:
    • Rheumatrex
  • Drug: Etanercept
    50 mg SC weekly
    Other names:
    • enbrel
  • Drug: Adalimumab
    40 mg SQ every other week
    Other names:
    • Humira

Recruiting Locations

University of Texas Health Science Center at Houston
Houston, Texas 77030
Contact:
Reyna Chavez
713-500-6870
Reyna.I.Chavez@uth.tmc.edu

More Details

NCT ID
NCT02374021
Status
Recruiting
Sponsor
Brigham and Women's Hospital

Study Contact

Daniel H Solomon
dsolomon@partners.org

Detailed Description

Consenting subjects will be screened for eligibility and randomized to a treatment arm. Subjects will be randomized to a treatment arm with either synthetic disease-modifying antirheumatic drugs (DMARDs) [triple therapy: sulfasalazine, methotrexate, and hydroxychloroquine] or biologic DMARDs [etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening].

Once randomized, a baseline visit will be conducted with each subject. Baseline data collection includes questionnaires, disease activity score, and the first FDG-PET/CT imaging. After the baseline at week 0, subjects will visit with their rheumatologist at weeks 6, 12, 18, and 24 for safety labs and further collection of disease activity scores and questionnaires. The second FDG-PET/CT will be performed at week 24. Blood specimens will be collected at weeks 0, 6, 18, and 24 for bioassays. Subject participation will end after the week 24 visit.

Patients and care providers will be unblinded. The FDG-PET/CT image readers will be blinded to treatment arm as well as timepoint of image acquisition.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.