Treatments Against RA and Effect on FDG-PET/CT (TARGET)

Mass General Brigham

Status and phase: Completed; Phase 4

Conditions: Arthritis, Rheumatoid

Treatments: Drug: Sulfasalazine; Drug: Methotrexate; Drug: Hydroxychloroquine; Drug: Etanercept; Drug: Adalimumab

Study type: Interventional

Funder types: Other

Identifiers

NCT02374021

2014P002747

Details and patient eligibility

About

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).

Full 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.

Enrollment: 159 patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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159 participants in 2 patient groups

Triple therapy (MTX+SSZ+HCQ)

Active Comparator group

Description:

Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).

Treatment:

Drug: Hydroxychloroquine

Drug: Methotrexate

Drug: Sulfasalazine

TNF inhibitor (etanercept or adalimumab)

Active Comparator group

Description:

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.

Treatment:

Drug: Adalimumab

Drug: Etanercept

Drug: Methotrexate