RA-PRO PRAGMATIC TRIAL

Rheumatoid Arthritis Clinical Trial

— RA-PROPR  

Official title:

A Real-World Comparative Effectiveness Trial of Treatment Strategies in Patients With Rheumatoid Arthritis: The RA-PRO Pragmatic Trial (RA-PROPR)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04692493
• Other study ID #: IRB-300006596
• Status: Recruiting
• Phase: Phase 3
• Start date: September 22, 2021
• Est. completion date: December 31, 2028

Study information

• Verified date: June 2024
• Source: University of Alabama at Birmingham
• Contact: Jasvinder Singh
• Phone: 205-975-2405
• Email: Jsingh[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 924
• Est. completion date: December 31, 2028
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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 ;

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.

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.

Exclusion Criteria:

1. 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• 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
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,

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital (Canada)	Toronto	Ontario
United States	East Alabama Arthritis Center PC	Auburn	Alabama
United States	George Munoz MD, PC	Aventura	Florida
United States	Johns Hopkins University	Baltimore	Maryland
United States	Bendcare, LLC	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts University	Boston	Massachusetts
United States	Southeast Georgia Physician Associates-Rheumatology	Brunswick	Georgia
United States	Indiana University Health	Carmel	Indiana
United States	American Arthritis and Rheumatology Associates LLC	Clearwater	Florida
United States	The MetroHealth System	Cleveland	Ohio
United States	University Hospital Cleveland Medical Ctr	Cleveland	Ohio
United States	Dr. Jayashree Sinha	Clovis	New Mexico
United States	Heritage Rheumatology and Arthritis Care	Colleyville	Texas
United States	CZ Rheumatology	Coral Springs	Florida
United States	Cumberland Rhematology	Crossville	Tennessee
United States	Southwest Medical Center	Dallas	Texas
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Saint Paul Rheumatology, P.A.	Eagan	Minnesota
United States	Texas Arthritis Center, PA	El Paso	Texas
United States	Rheumatology and Arthritis Care Center	Exton	Pennsylvania
United States	American Arthritis and Rheumatology Associates LLC	Fort Lauderdale	Florida
United States	American Arthritis and Rheumatology Associates-Tx PLLC	Harlingen	Texas
United States	Baylor University	Houston	Texas
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Palm Beach Rheumatology and Wellness	Jupiter	Florida
United States	Arthritis and Rheumatology of Southwest Ohio	Liberty Township	Ohio
United States	Pacific Arthritis Care Center	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Arthritis & Rheumatology Center of South Florida	Margate	Florida
United States	Life Medical Research Group	Miami Gardens	Florida
United States	Vanderbilt University	Nashville	Tennessee
United States	Hospital for Special Surgery	New York	New York
United States	New York University	New York	New York
United States	Arthritis Medical Center	Nipomo	California
United States	American Arthritis and Rheumatology Associates -Mi PLLC	Okemos	Michigan
United States	SunValley Arthritis Center, Ltd	Peoria	Arizona
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Northern Virginia Center for Arthritis-Reston	Reston	Virginia
United States	Southwest Florida Rheumatology	Riverview	Florida
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Inspire Santa Fe Medical Group	Santa Fe	New Mexico
United States	University of Arizona	Tucson	Arizona
United States	Turlock Arthritis & Osteoporosis Center,	Turlock	California
United States	Southern Ohio Rheumatology	Wheelersburg	Ohio
United States	Center for Rheumatology Research	Woodland Hills	California
United States	University of Massachusetts Chan Medical School	Worcester	Massachusetts
United States	PA Regional Center for Arthritis and Osteoporosis Research	Wyomissing	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Patient-Centered Outcomes Research Institute

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional Limitation	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.	Change from baseline to 12 months