Stopping TNF Alpha Inhibitors in Rheumatoid Arthritis

NCT01793519 | Active Not Recruiting Phase 4 DMC

• 2 other identifiers: CER-1402-1052213-AR-0056
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 2

Brief Summary

Background:

• Rheumatoid arthritis (RA) is often treated with drugs known as tumor necrosis factor (TNF) inhibitors, that can help decrease joint pain and swelling and can even result in RA remission. However, TNF inhibitors may increase risk of serious infections or some types of cancer.
• It is not clear if people whose RA has been in remission for a long time need to stay on the TNF inhibitor to remain in remission. If they can stop taking the TNF inhibitor without having their symptoms come back, they will be spared the side effects of these medicines. Some studies have shown that people can stay in remission after stopping a TNF inhibitor, but other studies have not confirmed it. Researchers want to see if people with RA in remission on a TNF inhibitor can stay in remission without this medicine. Also there may be a clinical, imaging (MRI, ultrasound), laboratory profile that will help to determine which patients remain in remission after stopping these drugs. Objectives:
• To see whether RA remission can continue after discontinuing use of a TNF inhibitor.
• To determine if clinical, imaging and immunological measurements can predict which participants will flare and which will remain in remission after discontinuing TNF inhibitor. Eligibility:
• Individuals at least 18 years of age who have RA that is being controlled with TNF inhibitors. We plan to randomize 291 patients. Design:
• The study has seven visits over about 2 years. Six visits occur in the first year of the study, about 12 weeks apart. The final study visit is 1 year after the end of the treatment phase.
• At the first visit, participants will be screened with a physical exam and medical history. They will complete a questionnaire about their RA symptoms. A blood sample will be collected. They will continue to take their RA medicines during this time.
• The second visit will repeat tests from the first visit. These tests will confirm that the RA is in remission. Imaging studies will be performed on the hands, wrists, feet, and their connected joints. After this visit, participants will stop taking their TNF inhibitors and will start to have injections of a study drug. This drug will be either the participant's original TNF inhibitor or a placebo.
• There will be follow-up visits at weeks 12, 24, and 36. Participants will have a medical history and joint exam. They will also provide blood samples and answer questions about their RA symptoms.
• At the sixth visit (week 48), participants will repeat the tests and imaging studies from the second visit. They will stop taking the study injections.
• Continued RA treatment after this visit will be decided by the participant and his or her rheumatologist. Participants may take any recommended medicine, including the TNF inhibitor they had been taking before the study. They will also receive a questionnaire to complete at home and mail back before the final study visit.
• At the final visit (week 100), participants will repeat the tests and imaging studies from the second and sixth visits.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Autoimmune Diseases; Anti-TNF

Outcome Measures

Primary Outcomes (1)

• Remission by Disease Activity Score - 28 over 48 weeks

  48 weeks

Secondary Outcomes (2)

• Change in Health Assessment Questionnaire Disability Index over 48 weeks

  48 weeks

• Change in Sharp-van der Heijde radiographic score over 48 weeks

  48 weeks

Study Arms (2)

Anti-tumor necrosis factor agent

ACTIVE COMPARATOR

Anti-TNF agent - etanercept, infliximab, adalimumab - administered parentally at standard dosage and frequencies

Drug: Etanercept; Drug: Infliximab; Drug: Adalimumab

Placebo

PLACEBO COMPARATOR

Administered appropriately to active comparator

Drug: Placebo

Interventions

Etanercept DRUG

Subcutaneous

Also known as: Enbrel

Anti-tumor necrosis factor agent

Infliximab DRUG

Infusion

Also known as: Remicade

Anti-tumor necrosis factor agent

Adalimumab DRUG

Subcutaneous

Also known as: Humira

Anti-tumor necrosis factor agent

Placebo DRUG

Matching Placebo

Placebo

Eligibility Criteria

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

You may not qualify if:

• At the screening visit, potential participants will be included if:
• Age greater than or equal to 18 years
• Have RA, as defined by the 1987 revised American College of Rheumatology criteria
• In sustained clinical remission for the last 6 months while receiving treatment with either etanercept, infliximab, or adalimumab, and greater than or equal to 1 DMARD (methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, minocycline, cyclosporine, azathioprine, gold, penicillamine). DAS28 should be less than 2.6 on each visit over the preceding 6 months, with at least one visit 2-4 months before enrollment. If there is no visit 6 months before enrollment, the nearest visit in the 6-12 month period before enrollment should be considered and have a DAS28 less than 2.6.
• Potential participants will be excluded if:
• Had dose increase of anti-TNF agent or DMARD in the last 6 months
• Had change of anti-TNF agent or DMARD in the last 6 months
• Treated currently with golimumab or certolizumab
• Treated with greater than 10 mg of prednisone (or equivalent) daily in the last 6 months
• Treated with greater than 5 mg of prednisone (or equivalent) daily in the last 3 months
• Treated with intramuscular or intravenous corticosteroids in the last 6 months for RA activity
• Treated with anakinra, abatacept, or tocilizumab in the last 6 months
• Treated with rituximab in the last 12 months
• Treated with an investigational RA drug in the last 6 months
• Pregnant (or anticipate pregnancy during the study period) or lactating women

Sponsors & Collaborators

• Georgetown University: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• University of Maryland, Baltimore: collaborator
• Washington D.C. Veterans Affairs Medical Center: collaborator
• Medstar Health Research Institute: collaborator
• Patient-Centered Outcomes Research Institute: collaborator
• Arthritis and Pain Associates of PG County: collaborator
• Arthritis & Rheumatism Associates, P.C.: collaborator
• Rheumatology Associates of Baltimore, L.L.C.: collaborator
• The Arthritis Clinic of Northern Virginia, P.C.: collaborator
• Arthritis and Rheumatic Disease Associates, P.C.: collaborator

Study Sites (2)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001 Mar 22;344(12):907-16. doi: 10.1056/NEJM200103223441207. No abstract available.

  PMID: 11259725 BACKGROUND

• Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, Heyse SP, Hirsch R, Hochberg MC, Hunder GG, Liang MH, Pillemer SR, Steen VD, Wolfe F. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998 May;41(5):778-99. doi: 10.1002/1529-0131(199805)41:53.0.CO;2-V.

  PMID: 9588729 BACKGROUND

• Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008 Jan;58(1):26-35. doi: 10.1002/art.23176.

  PMID: 18163497 BACKGROUND

• Ward MM, Weinstein A, Alejandro-Silva P, Matsumoto AK, Konatalapalli R, Stahl N, Kerr GS, Mikdashi J, Kempf P, Shah NR, Danielides S, Ghafouri M, Olenginski TP, Fike A, Balyozova-Dinkov D, Thiele R, Yao L, Paul S, Constantinescu F. Discontinuation versus continuation of maintenance treatment with tumor necrosis factor inhibitors in patients with rheumatoid arthritis with low disease activity or remission: A randomized double-blind placebo-controlled trial. Semin Arthritis Rheum. 2025 Dec;75:152831. doi: 10.1016/j.semarthrit.2025.152831. Epub 2025 Sep 17.

  PMID: 41045868 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Arthritis, Rheumatoid; Autoimmune Diseases

Interventions

Etanercept; Infliximab; Adalimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal; Antibodies; Antibodies, Monoclonal, Humanized

Study Officials

• Michael M Ward, M.D.

  National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

  PRINCIPAL INVESTIGATOR

• Florina Constantinescu, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: February 15, 2013
• Study Start: January 1, 2013
• Primary Completion: June 30, 2024
• Study Completion: August 30, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

US (2)