Treatments Against RA and Effect on FDG-PET/CT

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.

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)