Study Description

Rheumatoid arthritis (RA) is a chronic inflammatory disease, causing joint damage and disability. While remarkable progress in the treatment of RA over the past two decades has improved many outcomes, mortality rates in RA remain 1.5-3-fold above non-RA controls. Cardiovascular disease (CVD) is the leading cause of excess deaths in RA.  Most experts believe that enhanced vascular inflammation underpins accelerated atherosclerosis and CV events yet, there has been no direct proof for this hypothesis. If this is true, then RA therapies that reduce joint inflammation might also reduce CV risk. The lack of an RA-specific CV risk tool hampers evidence-based guidelines, as general population tools perform poorly in RA. These gaps in knowledge create uncertainty for patients and providers in managing RA and its comorbidities. This study proposes to use 18fluoro-deoxyglucose by positron emission tomography/computed tomography (FDG PET/CT) as a novel imaging modality to detect baseline, and disease-modifying antirheumatic drug (DMARD)-associated changes in, vascular inflammation in RA.

The study team will compare the effects on FDG PET/CT of 2 treatment regimens in an RCT among methotrexate (MTX) inadequate responders, representing a critical and common decision point for rheumatologists and patients: addition of a TNFi vs. sulfasalazine + hydroxychloroquine to background MTX. Recent RCTs show near equivalent reduction in articular disease activity, but the relative effects of these regimens on CV risk are unknown. Using data from the RCT, the study team will also compare the effects on vascular inflammation of achieving low disease activity or remission vs. remaining in moderate-high disease activity. These pre-specified secondary analyses will pool the treatment arms to examine whether achievement of a disease activity target associates with greater reduction in vascular inflammation.

ELIGIBILITY CRITERIA:

Ages Eligible for Study:           45 Years and older   (Adult, Older Adult)

Sexes Eligible for Study:          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:

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Single (Outcomes Assessor)

Primary Purpose: Treatment

Study Location(s):

University of Alabama at Birmingham, Birmingham, Alabama, United States, 35294

David Geffen School of Medicine at UCLA, Los Angeles, California, United States, 90095

Brigid Freyne, MD Inc. , Murrieta, California, United States, 92563

Desert Medical Advances, Palm Desert, California, United States, 92260

University of California San Francisco , San Francisco, California, United States, 94110

Nazanin Firooz MD, Inc., West Hills, California, United States, 91307

Robert W. Levin, MD, PA, Clearwater, Florida, United States, 33765

Southwest Florida Clinical Research Center, Tampa, Florida, United States, 33609

Northwestern University, Chicago, Illinois, United States, 60611

University of Kentucky, Lexington, Kentucky, United States, 40508

The Center for Rheumatology and Bone Research, Wheaton, Maryland, United States, 20902

Massachusetts General Hospital, Boston, Massachusetts, United States, 02114

Brigham and Women's Hospital, Boston, Massachusetts, United States, 02115

University of Michigan, Ann Arbor, Michigan, United States, 48109

Washington University Medical Center, Saint Louis, Missouri, United States, 63110

Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States, 03756

Jacobi Medical Center, Bronx, New York, United States, 10461

SUNY Downstate Medical Center, Brooklyn, New York, United States, 11203

Northwell Health, Great Neck, New York, United States, 11021

New York University School of Medicine, New York, New York, United States, 10003 

Mount Sinai- Icahn School of Medicine, New York, New York, United States, 10029

Columbia University Medical Center, New York, New York, United States, 10032

University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States, 27599

Cleveland Clinic, Cleveland, Ohio, United States, 44195

Oregon Health & Science University, Portland, Oregon, United States, 97329

Altoona Research Center, Duncansville, Pennsylvania, United States, 16635

University of Pennsylvania, Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States, 15261

Baylor Scott and White Research Institute, Dallas, Texas, United States, 75204

Metroplex Clinical Research Center, Dallas, Texas, United States, 75231

University of Texas Health Science Center at Houston, Houston, Texas, United States, 77030

Baylor Scott & White Medical Center- Temple, Temple, Texas, United States, 76508

Seattle Rheumatology Associates, Seattle, Washington, United States, 98122

University of Wisconsin- Madison, Madison, Wisconsin, United States, 53705

Study Website:

https://clinicaltrials.gov/ct2/show/NCT02374021?term=NCT02374021&rank=1