Analysis of T and B Cell Repertoire Changes in Response to Orencia® (Abatacept) in Rheumatoid Arthritis

NCT05782335 | Recruiting DMC

• 1 other identifier: 2021-0142
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The condition that will be studied is Rheumatoid Arthritis (RA), and in particular, RA patients with moderate to highly active disease who were prescribed Abatacept (Orencia®) (ABA) by their physician during their setting of care at Hospital for Special Surgery (HSS). This investigator-initiated, prospective, comparative, 3-arm observational study will examine changes in lymphocytes in RA patients starting abatacept compared to RA patients starting TNF inhibitors and to healthy controls. This will help investigators to learn more about the processes that cause joints to swell and hurt. This may also offer clues that might predict which patients will have a good or poor response to these treatments.

Conditions

Rheumatoid Arthritis

Keywords

abatacept; b cell repertoire; t cell repertoire

Outcome Measures

Primary Outcomes (1)

• Change in clonotype diversity of T cell and B cell repertoires

  Investigators will compare the change in clonotype diversity of T cell and B cell repertoires in patients over 6 months by analyzing clonotype diversity of T cell and B cell repertoires at BL (pre-treatment), 3 months, and 6 months post treatment for each individual in each of the three groups (RA starting ABA; RA on stable MTX +/- TNFi.

  April 2024-March 2025

Secondary Outcomes (3)

• CTLA4 gene expression in peripheral blood at 3 times points

  April 2024-March 2025

• Changes in the proportions of T and B cell subtypes

  April 2024-March 2025

• Expression levels in peripheral blood of genes key to the immune response.

  April 2024-March 2025

Other Outcomes (6)

• T cell and B cell repertoire changes and CDAI

  April 2024-March 2025

• T cell and B cell repertoire changes and SDAI.

  April 2024-March 2025

• T cell and B cell repertoire changes and DAS23-ESR.

  April 2024-March 2025

Study Arms (3)

Arm 1: Abatacept Initiator

RA patients of any disease duration, 18 years or older who are starting ABA (either IV or subcutaneous at standard doses) for the first time. Concomitant non-biologic medications (for e.g., standard conventional synthetic (cs)DMARDs, one of which must be MTX as typically used in routine care, or if MTX was not tolerated leflunomide will be acceptable) will be allowed as long as the dose has been stable for at least 3 months.

Arm 2: csDMARD/TNFi Treated

RA patients, 18 years or older and on stable doses of conventional DMARDs (MTX with or without hydroxychloroquine, sulfasalazine, with or without leflunomide therapy, where leflunomide therapy can be an alternate to MTX). Patient's disease activity can be controlled or near controlled (CDAI \<=12) or active if a recent DMARD or TNFi has been added, though they will have been on MTX at doses of at least 15mg weekly or leflunomide 10 mg or more for 4 weeks or more. A combination of csDMARDs at stable doses for 4 or more weeks with \>= MTX 10 mg weekly or ± MTX 10 mg weekly for at least 4 weeks with any dose of a conventional TNF inhibitor (stable dose + TNFi) is permitted.

Arm 3. Healthy Controls

Healthy individuals over 18 y.o. without RA, SLE, juvenile arthritis, psoriasis or psoriatic arthritis or other inflammatory auto-immune rheumatic disease, who are receiving care at the HSS or volunteers from the community. Participants will be recruited to serve in the control population for this study. Given that the range of age for most RA patients is between 40-70, we will aim to recruit control volunteers in this age range, ensuring that at least 60% - 70% are female, ensuring an age range and sex that is proportionately similar to the RA population at HSS.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population is patients with RA who are starting ABA. Data from the study population will be compared with RA controls being treated with standard of care therapy, i.e., MTX with or without either other conventional synthetic (cs)DMARDs and/or a TNF inhibitor (etanercept, adalimumab, golimumab, infliximab, certolizumab pegol). RA patients who enter the study must meet inclusion criteria.

You may qualify if:

• \. Patients being treated with MTX with or without csDMARDS at stable doses for at least 4 weeks, who are either: (a) about to start ABA, OR, (b) who are likely to remain on stable DMARDs and who might also be using a TNFi but in whom all therapies will have been stable for 4 or more weeks.
• ) meet diagnostic criteria for RA, based on 2010 ACR Criteria or 1987 RA criteria, OR, are one point short of meeting the criteria but are being treated for RA, OR, have previously identified RA typical erosions.
• \) have never received ABA or rituximab, and, if previously used a JAKi, will have stopped this for over a month, OR, if previously used an IL-6 inhibitor, will have stopped for at least 3 months.
• \) RA subject must not be taking prednisone at doses over 10 mg daily, and will not have received injectable Depomedrol or equivalent within 4 weeks of baseline or prior to the 3 or 6 month study assessment. Healthy control patients cannot be taking prednisone. Any subject can use oral or nasal inhalers that include glucocorticoids 5) have evidence of recent or currently active disease depending on treatment arm. Subjects starting ABA (Arm 1) are expected to have at least moderate disease activity, OR if CDAI is between 2.81 and 10, there should be two or more swollen and tender joints. For subjects being included in Arm 2, the stable treatment arm, CDAI \<13 and one swollen joint observed by a rheumatologist in the prior 6 months. Subjects recruited to the healthy control arm (Arm 3) will be free of any autoimmune disease or systemic form of an inflammatory arthritis.
• \) WOCBP must be using acceptable forms of contraception to avoid pregnancy throughout the study, i.e. oral contraceptives, other hormonal contraceptives.

You may not qualify if:

• Have severe complications of RA that might require imminent escalation of therapy, e.g. pericarditis, active vasculitis of a major organ system.
• Have an autoimmune disease or systemic inflammatory rheumatic disease (e.g., lupus erythematosus) that could confound T and B cell subset results
• Have a concurrent serious medical disease (e.g., terminal malignancy)
• Have a BMI indicating poor health (\<18 or \> 40)
• Have received the following Prohibited Treatments and/or Therapies
• treatment with rituximab
• exposed to ABA or CTLA-4Ig
• exposed to any investigational drug within 28 days.
• received any live vaccines within 2 weeks prior to study start. Subjects cannot receive a live vaccine at any time during the study.
• WOCBP with a positive pregnancy test on enrollment or prior to study start, OR who are unwilling or unable to use an acceptable method to avoid pregnancy despite continuing MTX.
• part of a vulnerable population

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood sample prior to infusion at all visits,

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

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

Study Officials

• Louis Bridges, MD PhD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

• Vivian P Bykerk, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Margaret Butler, BS

CONTACT

917-260-4906; ButlerM@hss.edu

Caroline Reidy, MPH

CONTACT

646-704-3426; ReidyC@hss.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: March 23, 2023
• Study Start: November 1, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)