People-Powered Medicine (PPM): Rheumatoid Arthritis Non-responders to Biologic Therapies (RANT) (PPM:RANT)

The investigators are interested in enrolling patients with rheumatoid arthritis (RA) who had a difficult time getting their disease under control even after trying multiple RA therapies. The investigators believe that there may be common patterns in the genes of this group of RA patients compared to those with more "textbook RA." Understanding genetic factors can help doctors to know in advance who may not respond to conventional therapies and start with treatments that work. Learning about underlying genes that influence treatment may help the investigators to identify new targets for therapy, to ultimately improve the lives of patients with RA and inflammatory arthritis.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis

Detailed Description

The investigators are looking for patients with rheumatoid arthritis (RA) with an inadequate response to tumor necrosis factor inhibitor (TNFi) and another biologic disease modifying anti-rheumatic drug (bDMARD) or small molecule approved for treating RA. The investigators are conducting this research to learn more about RA and the genetic patterns associated with patients whose RA cannot be well controlled with most RA treatments. Investigators anticipate that these patients will differ from "classic" RA patients in their biomarker and genetic composition and that they represent a mixed group of individuals who may be similar in ways that are not currently being measured.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients diagnosed with rheumatoid arthritis (RA) that have failed TNFi therapy and another bDMARD or small molecule approved for RA.

TNFi= adalimumab (Humira), certolizumab (Cimzia), etanercept (Enbrel), infliximab (Remicade), golimumab (Simponi)

bDMARDs or small molecules for RA in addition to TNFi above: abatacept (Orencia), baricitinib (Olumiant), sarilumab (Kevzara), tocilizumab (Actemra), rituximab (Rituxan), tofacitinib (Xeljanz), upadacitinib (Rinvoq)

Description

Inclusion Criteria:

• Age > 18 years
• RA diagnosed by a rheumatologist
• Poor control of RA disease activity with tumor necrosis factor inhibitor (TNFi) and another biologic therapy or small molecule approved for RA

Exclusion Criteria:

• If the reason for failed TNFi therapy was due to a contraindication or adverse reaction
• Unable to provide blood sample

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole genome sequencing	Genomic data will be applied in an established bioinformatics pipeline to screen for uncommon variants and test association with exceptional treatment non-responders compared with TNFi responders.	Through study completion, averaging 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup analyses of treatment non-responders	Patients who eventually find a therapy that controls their RA. The investigators will use prospective questionnaire data to subgroup patients into those who eventually find a treatment that works vs those who do not.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other potential predictors of poor response to biologic therapies	Electronic health data will be used to assess for common features of patients who have poor response to therapy compared to TNFi responders.	Retrospective data up to 10 years prior to enrollment

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Harvard Medical School (HMS and HSDM)

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: August 5, 2021
• First Submitted That Met QC Criteria: July 1, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Treatment non-response; Tumor necrosis factor inhibitor (TNFi); Disease modifying anti-rheumatic therapy; Biologic therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: IRB20-1219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No