Safety of TofAcitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA)- Cardiovascular Endpoints

NCT04772248 | Completed FDA Drug

• 1 other identifier: 2011P002580-202
• Study Type: observational
• Target: 105,711
• Locations: 1 country
• Sites: 1

Brief Summary

There are two main aims of this study. First aim is to compare the risk of cardiovascular events (including myocardial infarction or stroke), between patients treated with tofacitinib and patients treated with TNF inhibitors (TNFi) for rheumatoid arthritis (RA) among, 1) "real world evidence (RWE)" cohorts including routine care patient population from the US and, 2) "Randomized controlled trial (RCT) DUPLICATE" cohorts including routine care patient population who meet inclusion and exclusion criteria of the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis ("ORAL Surveillance", NCT02092467) clinical trial. Second aim is to examine the risk of myocardial infarction, stroke, heart failure hospitalization, coronary revascularization, and all-cause mortality as separate endpoints when comparing tofacitinib with TNFi in patients with RA among, 1) "real world evidence (RWE)" cohort including routine care patient population from the US and, 2) "Randomized controlled trial (RCT) DUPLICATE" cohort including routine care patient population who meet inclusion and exclusion criteria of the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis ("ORAL Surveillance", NCT02092467) clinical trial.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Time to first composite cardiovascular endpoint consisting of myocardial infarction or stroke

  Myocardial infarction OR Stroke

  Through study time period (2012-2020)

Secondary Outcomes (5)

• Time to myocardial infarction

  Through study time period (2012-2020)

• Time to stroke

  Through study time period (2012-2020)

• Time to heart failure hospitalization

  Through study time period (2012-2020)

• Time to coronary revascularization

  Through study time period (2012-2020)

• Time to all-cause mortality

  Through study time period (2012-2020)

Study Arms (2)

Patients treated with Tofacitinib

Real-World Evidence (RWE) and RCT-Duplicate

Drug: Tofacitinib

Patients treated with TNF inhibitors

Real-World Evidence (RWE) and RCT-Duplicate

Drug: TNF Inhibitor

Interventions

Tofacitinib DRUG

First eligible prescription for treating rheumatoid arthritis (RA)

Patients treated with Tofacitinib

TNF Inhibitor DRUG

First eligible prescription for treating rheumatoid arthritis (RA)

Also known as: infliximab, adalimumab, certolizumab pegol, etanercept, golimumab

Patients treated with TNF inhibitors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

There will be two independent study populations: 1. Real-World Evidence (RWE) cohorts: This study population will reflect the patients diagnosed with RA who are routinely treated and managed in setting of clinical practice. 2. RCT-duplicate cohorts: This study population will emulate "the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis" clinical trial ("ORAL Surveillance", NCT02092467). The inclusion and exclusion criteria of this RCT will be applied to this study population.

You may not qualify if:

• Patients treated with tofacitinib or TNF inhibitors in IBM MarketScan, Optum, and Medicare fee-for-service
• A minimum of 365 days of continuous enrollment in health plan prior to (and including) the cohort entry date
• Two diagnosis codes for RA in any setting in 365 days baseline period (diagnosis codes between 7 and 365 days apart)
• Index drug in 365 days prior to cohort entry date (prevalent users)
• Missing data on age or gender
• Admission to nursing facility or hospice on or prior to cohort entry date (ever look-back)
• TNFi users with history of any Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib, or baricitinib) (ever look-back period)
• TNFi users initiating with more than one TNFi on same date
• Tofacitinib users with a prescription of baricitinib, upadacitinib (ever look-back period)
• Tofacitinib users initiating treatment on multiple JAK inhibitors on same day (tofacitinib and baricitinib, tofacitinib and upadacitinib)
• Patients less than 18 years of age (MarketScan and Optum) and 65 years of age (Medicare) at cohort entry
• Patients with at least one methotrexate dispensation (six months look-back period)
• Patients with at least one cardiovascular risk factor (including smoking, hypertension, dyslipidemia, diabetes mellitus, ischemic heart disease, family history of ischemic heart disease) (one-year look-back period)
• Patients less than 50 years of age (MarketScan and Optum) and 65 years
• Patients recently hospitalized with infections (30-day look-back period)

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham And Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Related Publications (1)

• Khosrow-Khavar F, Kim SC, Lee H, Lee SB, Desai RJ. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 Jun;81(6):798-804. doi: 10.1136/annrheumdis-2021-221915. Epub 2022 Jan 13.

  PMID: 35027405 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib; Tumor Necrosis Factor Inhibitors; Infliximab; Adalimumab; Certolizumab Pegol; Etanercept; golimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Fc Fragments; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Rishi Desai, MS, PhD

  Assistant Professor of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: February 26, 2021
• Study Start: February 22, 2021
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2021
• Last Updated: March 2, 2022

Record last verified: 2022-03

Locations

US (1)