RA-PRO PRAGMATIC TRIAL
- Conditions
- Rheumatoid Arthritis
- Interventions
- Drug: targeted synthetic DMARD classDrug: non-TNFi-biologic class
- Registration Number
- NCT04692493
- Lead Sponsor
- University of Alabama at Birmingham
- Brief Summary
The 2021 ACR RA treatment guideline, based on widely acknowledged low to moderate quality evidence, recommends switching to a non-tumor necrosis factor (TNFi) biologic (choose among existing medications, currently, rituximab, abatacept, tocilizumab, or sarilumab) or a targeted synthetic DMARD arm (tsDMARD; choose among existing medications, currently, tofacitinib, baricitinib, upadacitinib) in patients with active RA despite the use of a TNFi-biologic. In practice, most patients receive another TNFi-biologic, i.e., a second TNFi-biologic first. This is not based on solid evidence, but on arbitrary algorithms often proposed by health insurance plans, and/or physician experience and habit (TNFis launched 22 yrs ago vs. the first tsDMARD 8 years ago vs. first non-TNF-biologic launched 17 years ago). This study will fill a critical knowledge gap by generating CER data for important PROs between these treatment options, switching to a non-TNFi biologic or a tsDMARD in patients with active RA despite the use of a TNFi-biologic.
- Detailed Description
Treatment of RA with a non-TNFi biologic (rituximab, abatacept, tocilizumab, or sarilumab) was associated with improved function, quality of life, and productivity. TsDMARDs (tofacitinib, baricitinib, upadacitinib) were similarly effective. No meaningful differences were noted in non-TNFi-biologic vs. tsDMARD, but head-to-head studies of biologics are lacking. HAQ is a sensitive outcome for RA trials. A PCORI systematic review for early RA treatment concluded that "Evidence was insufficient to evaluate any differences between biologics for their impact on either functional capacity or HRQOL", a key knowledge gap our study will fill.
The 2021 ACR RA treatment guideline, based on widely acknowledged low to moderate quality evidence, recommends switching to a non-TNFi biologic or a tsDMARD in patients with active RA despite the use of a TNFi-biologic. In practice, most patients receive another TNFi-biologic first, i.e., a second TNFi. This is not based on solid evidence, but on arbitrary algorithms often proposed by health insurance plans, and physician experience (first TNFi launched 22 yrs ago vs. the first tsDMARD 8 yrs ago vs. first non-TNF-biologic launched 17 years ago). This study will fill a critical knowledge gap by generating CER data for important PROs between these treatment options. This will facilitate informed decision-making, since PROs may be more sensitive to different mechanisms of action, and are highly relevant to patients.
The proposed study will also provide needed evidence for real-world treatment decisions made by public and private payers. This head-to-head pragmatic trial will be the first to provide CER data for improvement in key PROs with recommended strategies in active RA despite the use of a TNFi-biologic and addresses PCORI and IOM priority areas by comparing the two most commonly used RA treatment strategies for people with active RA despite the use of a TNFi-biologic. This research is patient-centered, as study outcomes were identified by patients and payers. Currently, treatment choices are based on physician experience and insurance payer limitations. Investigators will generate evidence to help patients make decisions for themselves based on outcomes they care most about based on the relative efficacy of outcomes.
Investigators will: (1) compare improvements in PROs with RA treatment strategies to each other using a state-of-the-art real-world pragmatic effectiveness study design, which will for the first time include most RA patients with comorbidities;(2) compare their toxicity in a real-world population for TNFi-biologic vs. tsDMARD. To our knowledge, no previous RCT comparing these drugs has examined a PRO as a primary outcome in RA, which our study will pioneer by using HAQ. HAQ is sensitive to change with effective treatments.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 924
- Patients with active, disabling RA (CDAI ≥10 and HAQ ≥0.5) despite the use/experience for ≥ 3 months of a TNFi-biologic OR discontinued the medication(s) due to intolerability or toxicity irrespective of treatment duration prior to the first dose of study drug ;
- If receiving glucocorticoids (≤10 mg/day of prednisone of equivalent) or NSAIDs, on stable doses for ≥2 weeks prior to randomization; and
- Insurance plan or patient assistance program allows access to at least 1 drug in each of the two treatment strategies, TNFi-biologic vs. tsDMARD.
Participants will be allowed to continue their conventional synthetic DMARD (csDMARD) therapy if they had been using it for ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, and leflunomide (TNFi-biologic and tsDMARD) through insurance plan or a patient assistance program/plan.
- Prior treatment with more than three biologics, defined as TNFi-biologic or non-TNFi biologic
- Prior treatment with targeted synthetic DMARD
- Concomitant use of leflunomide, sulfasalazine, cyclosporine, or azathioprine within 2-months before randomization;
- History of sensitivity to all 4 non-TNF-biologic or a targeted synthetic DMARD;
- Glucocorticoid injection (intravenous, intramuscular, or intraarticular) within 1 month of study entry;
- Live vaccine within 90 days of study entry;
- Acute or chronic infections with parenteral antibiotics or hospitalization (including tuberculosis, bacterial sepsis; invasive fungal infections (such as histoplasmosis)) within 1 month or oral antibiotics within 2 weeks of study entry;
- History of HIV or any opportunistic infection;
- New York Heart Association Class III or IV heart failure;
- Latent TB for which anti-tubercular treatment has not been started;
- Untreated Hepatitis B or C infection;
- History of deep venous thrombosis or pulmonary embolism; or
- Pregnant or nursing women; or
- History of herpes zoster or shingles.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description targeted synthetic DMARD class targeted synthetic DMARD class Switching to a targeted synthetic DMARD (choice from targeted synthetic DMARDs; currently available are tofacitinib, baricitinib, upadacitinib) in people with active RA despite current treatment non-TNFi-biologic class non-TNFi-biologic class Switching to a non-TNFi-biologic (choice from non-TNFi-biologics; currently available are rituximab, abatacept, tocilizumab, or sarilumab) in people with active RA despite current treatment,
- Primary Outcome Measures
Name Time Method Functional Limitation Change from baseline to 12 months Function limitation assessed by Health assessment questionnaire (HAQ); HAQ assesses difficulty in 20 items in 8 categories (dressing, arising, eating, walking, hygiene, reaching, gripping, and outside activity), the total score ranges from 0 (no disability) to 3 (complete disability). Higher score is worse, and indicates poor function.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (48)
University of Massachusetts Chan Medical School
🇺🇸Worcester, Massachusetts, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Tufts University
🇺🇸Boston, Massachusetts, United States
George Munoz MD, PC
🇺🇸Aventura, Florida, United States
SunValley Arthritis Center, Ltd
🇺🇸Peoria, Arizona, United States
East Alabama Arthritis Center PC
🇺🇸Auburn, Alabama, United States
Center for Rheumatology Research
🇺🇸Woodland Hills, California, United States
Palm Beach Rheumatology and Wellness
🇺🇸Jupiter, Florida, United States
Pacific Arthritis Care Center
🇺🇸Los Angeles, California, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
American Arthritis and Rheumatology Associates -Mi PLLC
🇺🇸Okemos, Michigan, United States
Southern Ohio Rheumatology
🇺🇸Wheelersburg, Ohio, United States
PA Regional Center for Arthritis and Osteoporosis Research
🇺🇸Wyomissing, Pennsylvania, United States
Inspire Santa Fe Medical Group
🇺🇸Santa Fe, New Mexico, United States
Heritage Rheumatology and Arthritis Care
🇺🇸Colleyville, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Baylor University
🇺🇸Houston, Texas, United States
Southwest Florida Rheumatology
🇺🇸Riverview, Florida, United States
New York University
🇺🇸New York, New York, United States
Saint Paul Rheumatology, P.A.
🇺🇸Eagan, Minnesota, United States
Southwest Medical Center
🇺🇸Dallas, Texas, United States
Bendcare, LLC
🇺🇸Birmingham, Alabama, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Indiana University Health
🇺🇸Carmel, Indiana, United States
University Hospital Cleveland Medical Ctr
🇺🇸Cleveland, Ohio, United States
American Arthritis and Rheumatology Associates-Tx PLLC
🇺🇸Harlingen, Texas, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Allegheny Health Network
🇺🇸Pittsburgh, Pennsylvania, United States
The MetroHealth System
🇺🇸Cleveland, Ohio, United States
Dr. Jayashree Sinha
🇺🇸Clovis, New Mexico, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Southeast Georgia Physician Associates-Rheumatology
🇺🇸Brunswick, Georgia, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Northern Virginia Center for Arthritis-Reston
🇺🇸Reston, Virginia, United States
Mount Sinai Hospital (Canada)
🇨🇦Toronto, Ontario, Canada
Cumberland Rhematology
🇺🇸Crossville, Tennessee, United States
Rheumatology and Arthritis Care Center
🇺🇸Exton, Pennsylvania, United States
Arthritis Medical Center
🇺🇸Nipomo, California, United States
Turlock Arthritis & Osteoporosis Center,
🇺🇸Turlock, California, United States
Arthritis & Rheumatology Center of South Florida
🇺🇸Margate, Florida, United States
American Arthritis and Rheumatology Associates LLC
🇺🇸Fort Lauderdale, Florida, United States
CZ Rheumatology
🇺🇸Coral Springs, Florida, United States
Life Medical Research Group
🇺🇸Miami Gardens, Florida, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Arthritis and Rheumatology of Southwest Ohio
🇺🇸Liberty Township, Ohio, United States
Texas Arthritis Center, PA
🇺🇸El Paso, Texas, United States