RA-PRO PRAGMATIC TRIAL
Purpose
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.
Condition
- Rheumatoid Arthritis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Patients with active, disabling RA (CDAI ≥10 and HAQ ≥0.5) despite the use/experience 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 ; 2. If receiving glucocorticoids (≤10 mg/day of prednisone of equivalent) or NSAIDs, on stable doses for ≥2 weeks prior to randomization; and 3. Insurance plan or patient assistance program allows access to at least 1 drug in each of the two treatment strategies, TNFi-biologic vs. tsDMARD.(TNFi-biologic and tsDMARD) will be obtained through insurance plan or a patient assistance program/plan. 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
Exclusion Criteria
- Prior treatment with more than three biologics, defined as TNFi-biologic or non-TNFi biologic 2. Prior treatment with targeted synthetic DMARD 3. Concomitant use of leflunomide, sulfasalazine, cyclosporine, or azathioprine within 2-months before randomization; 4. History of sensitivity to all 4 non-TNF-biologic or a targeted synthetic DMARD; 5. Glucocorticoid injection (intravenous, intramuscular, or intraarticular) within 1 month of study entry; 6. Live vaccine within 90 days of study entry; 7. 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; 8. History of HIV or any opportunistic infection; 9. New York Heart Association Class III or IV heart failure; 10. Latent TB for which anti-tubercular treatment has not been started; 11. Untreated Hepatitis B or C infection; 12. History of deep venous thrombosis or pulmonary embolism; or 13. Pregnant or nursing women; or 14. History of herpes zoster or shingles in the previous 12 months and not subsequently vaccinated with herpes zoster vaccine.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator 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 |
|
|
Active Comparator 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, |
|
Recruiting Locations
Auburn 4830796, Alabama 4829764 36830
Birmingham 4049979, Alabama 4829764 35244
Howard Busch, MD
Birmingham 4049979, Alabama 4829764 35294
Peoria 5308480, Arizona 5551752 85381
Tucson 5318313, Arizona 5551752 85724
Kent C Kwoh, MD
Los Angeles 5368361, California 5332921 90045
Dan Furst, MD
Los Angeles 5368361, California 5332921 90095
Veena K. Ranganath, MD
Nipomo 5377100, California 5332921 93444
Turlock 5404024, California 5332921 95382
Woodland Hills 5410438, California 5332921 91364
Aventura 4146429, Florida 4155751 33180
Clearwater 4151316, Florida 4155751 33765
Coral Springs 4151909, Florida 4155751 33065
Fort Lauderdale 4155966, Florida 4155751 33309
Jacksonville 4160021, Florida 4155751 32224
Vikas Majithia, MD
Jupiter 4160610, Florida 4155751 33458
Margate 4163407, Florida 4155751 33063
Miami Gardens 4164167, Florida 4155751 33014
Riverview 4170156, Florida 4155751 33569
Brunswick 4184845, Georgia 4197000 31520
Carmel 4255466, Indiana 4921868 46280
Baltimore 4347778, Maryland 4361885 21224
Uzma Haque, MD
Boston 4930956, Massachusetts 6254926 02111
Sreelakshmi Panginikkod, MD
Worcester 4956184, Massachusetts 6254926 01655
Jonathan Kay, MD
Okemos 5004359, Michigan 5001836 48864
Eagan 5024825, Minnesota 5037779 55121
Rochester 5043473, Minnesota 5037779 55905
Lynne Peterson, MD
Clovis 5462393, New Mexico 5481136 88101
Santa Fe 5490263, New Mexico 5481136 87505
New York 5128581, New York 5128638 10016
Pamela Rosenthal, MD
New York 5128581, New York 5128638 10021
Susan Goodman, MD
Cleveland 5150529, Ohio 5165418 44106
Marina N Magrey, MD
Cleveland 5150529, Ohio 5165418 44109
Nora Singer, MD
Liberty Township 7126297, Ohio 5165418 45069
Wheelersburg 4528203, Ohio 5165418 45694
Portland 5746545, Oregon 5744337 97239
Cong-Qiu Chu, MD
Duncansville 5187508, Pennsylvania 6254927 16635
Alan J Kivitz, MD, CPI
Exton 5189022, Pennsylvania 6254927 19341-2547
Pittsburgh 5206379, Pennsylvania 6254927 15212
Wyomissing 5220248, Pennsylvania 6254927 19610
Crossville 4616470, Tennessee 4662168 38555
Nashville 4644585, Tennessee 4662168 37235
Kevin W Byram, MD
Colleyville 4682478, Texas 4736286 76034
Dallas 4684888, Texas 4736286 75235
El Paso 5520993, Texas 4736286 77902
Harlingen 4696233, Texas 4736286 78550
Houston 4699066, Texas 4736286 77030
Reston 4781530, Virginia 6254928 20190
More Details
- NCT ID
- NCT04692493
- Status
- Recruiting
- Sponsor
- University of Alabama at Birmingham
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.