Treatments Against RA and Effect on FDG-PET/CT
- Conditions
- Arthritis, Rheumatoid
- Interventions
- Registration Number
- NCT02374021
- Lead Sponsor
- Brigham and Women's Hospital
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 159
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Triple therapy (MTX+SSZ+HCQ) Sulfasalazine Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]). Triple therapy (MTX+SSZ+HCQ) Methotrexate Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]). Triple therapy (MTX+SSZ+HCQ) Hydroxychloroquine Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]). TNF inhibitor (etanercept or adalimumab) Methotrexate 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. TNF inhibitor (etanercept or adalimumab) Etanercept 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. TNF inhibitor (etanercept or adalimumab) 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 6 Months 0, 6 months The primary outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of of the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The index vessel is the vessel (either aorta, left carotid, or right carotid) with the highest meanmaxTBR at baseline. Higher values indicate greater vascular inflammation.
FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
- Secondary Outcome Measures
Name Time Method Change From Baseline in the Average TBR of the Aorta 0, 6 months The outcome was the change in the target to background ratio (TBR) of the aorta as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation.
FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.Change From Baseline in the Average TBR of the Bilateral Carotids 0, 6 months The outcome was the change in the target to background ratio (TBR) of the average of the left and right carotids as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The baseline values of the left and right carotids were averaged and then the follow-up values of the left and right carotids were averaged resulting in one value at each time point. Higher values indicate greater vascular inflammation.
FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.Change From Baseline in the Average TBR of the Index Vessel 0, 6 months The outcome was the change in the target to background ratio (TBR) in the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation.
FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.Change From Baseline in the MDS of the Aorta 0, 6 months The outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of the aorta as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation.
FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
Trial Locations
- Locations (31)
IRIS Research and Development
🇺🇸Plantation, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Mount Sinai- Icahn School of Medicine
🇺🇸New York, New York, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Northwell Health
🇺🇸Great Neck, New York, United States
Baylor Scott & White Medical Center- Temple
🇺🇸Temple, Texas, United States
Altoona Research Center
🇺🇸Duncansville, Pennsylvania, United States
New York University School of Medicine
🇺🇸New York, New York, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Metroplex Clinical Research Center
🇺🇸Dallas, Texas, United States
Loma Linda University Clinical Trial Center
🇺🇸Loma Linda, California, United States
Brigid Freyne, MD Inc.
🇺🇸Murrieta, California, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Desert Medical Advances
🇺🇸Palm Desert, California, United States
Robert W. Levin, MD, PA
🇺🇸Clearwater, Florida, United States
Nazanin Firooz MD, Inc.
🇺🇸West Hills, California, United States
The Center for Rheumatology and Bone Research
🇺🇸Wheaton, Maryland, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Washington University Medical Center
🇺🇸Saint Louis, Missouri, United States
Seattle Rheumatology Associates
🇺🇸Seattle, Washington, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Southwest Florida Clinical Research Center
🇺🇸Tampa, Florida, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States