Comparison of the Tuberculin Skin Test (TST) and QuantiFERON ®-TB Gold Test (QFT-G) In Patients With Rheumatoid Arthritis Being Considered for Anti-TNF-Alpha Therapy

NCT00925249 | Unknown DMC

• 1 other identifier: 6950
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This research will help doctors interested in the usefulness of a new test to discover hidden tuberculosis infections in patients diagnosed with rheumatoid arthritis (RA). This new test is called Quantiferon-Gold (QFT-G). After immune system medicines that block TNF-alpha (a protein manufactured by white blood cells to stimulate and activate the immune system in response to infection or cancer) started to be used, the rate of tuberculosis infections in patients treated with these medicines has increased. Doctors think that the investigators may be missing some tuberculosis infections that were hidden before the medicine is started. This new QFT-G test might better diagnose these hidden tuberculosis infections than the current tuberculosis skin test, also known as a PPD/TST. The investigators would like to compare these two tests to find out which is better at detecting these hidden infections. At the same time the investigators will measure the strength of the patient's immune system with a blood test. If you are being considered for a TNF-alpha inhibitor medicine, or are getting the patient's routine PPD/TST, the investigators are asking for the patient's participation.

Conditions

Rheumatoid Arthritis; Tuberculosis

Keywords

rheumatoid arthritis; RA; TB; tuberculosis; anti-TNF therapy; biologic therapy; quantiferon; IGRA; Newly diagnosed rheumatoid arthritis (RA) in the Tricare system

Outcome Measures

Primary Outcomes (1)

• Primary endpoints are the results of the QFT-G test (defined as positive, negative or indeterminate) and the results of the TST (defined as positive or negative).

  Patients will be enrolled over a 2 year time frame

Secondary Outcomes (1)

• Secondary endpoints include the percentage and numbers of CD45RO (memory T cells), the response PHA intradermal antigen placement, numbers of hypoergic TSTs, and the results of cell mediated immunity (CMI) assays.

  Patients will be enrolled over a 2 year time period

Study Arms (2)

1

The study group will consist of RA patients of the Walter Reed Army Medical Center (WRAMC) rheumatology clinic being considered for treatment with anti-TNF alpha therapy. We will enter patients into the study over a projected course of 12-24 months or until we reach the statistical requirement of 60 subjects.

2

The control group will consist of healthy subjects without known immune-dysregulation or history of treatment with biologic agents who present to the WRAMC Allergy- Immunology clinic for routine screening TST as a part of current WRAMC policy.

Eligibility Criteria

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

Study Population

patients in the US government tricare health system

You may qualify if:

• Study group:
• Any patient 18 years or older who has been diagnosed with RA (American College of Rheumatology (ACR) criteria) and is being considered for de novo anti-TNF alpha therapy will be invited to participate in this study.
• Control group:
• Control subjects will be any patient 18 years or older presenting to the Allergy/Immunology clinic for routine TST.

You may not qualify if:

• Study group:
• We will exclude any individual with a previous history of known immuno-compromising disease state or unstable medical condition other than RA resulting in overall poor health and/or protein calorie deprivation to include:
• any other autoimmune disease
• oral steroid use in the past 3 days (4 half-lives of prednisone is 14 hours)
• inhaled steroid use at a dose of \> 2000 mg beclomethasone equivalent/day
• any cancer \[solid organ or blood\]
• radiation therapy in prior three months
• any bleeding disorders
• chemotherapeutic agents
• transfusion or blood products in past 1 year
• history of HIV
• chronic hepatitis
• malignancy
• transplant history
• chronic infection

Sponsors & Collaborators

• Walter Reed Army Medical Center: lead
• National Naval Medical Center: collaborator

Study Sites (1)

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307, United States

RECRUITING

Related Publications (9)

• Greenberg JD, Reddy SM, Schloss SG, Kurucz OS, Bartlett SJ, Abramson SB, Bingham CO 3rd. Comparison of an in vitro tuberculosis interferon-gamma assay with delayed-type hypersensitivity testing for detection of latent Mycobacterium tuberculosis: a pilot study in rheumatoid arthritis. J Rheumatol. 2008 May;35(5):770-5.

  PMID: 18322990 BACKGROUND

• Gomez-Reino JJ, Carmona L, Valverde VR, Mola EM, Montero MD; BIOBADASER Group. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum. 2003 Aug;48(8):2122-7. doi: 10.1002/art.11137.

  PMID: 12905464 BACKGROUND

• Carmona L, Gomez-Reino JJ, Rodriguez-Valverde V, Montero D, Pascual-Gomez E, Mola EM, Carreno L, Figueroa M; BIOBADASER Group. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum. 2005 Jun;52(6):1766-72. doi: 10.1002/art.21043.

  PMID: 15934089 BACKGROUND

• British Thoracic Society Standards of Care Committee. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment. Thorax. 2005 Oct;60(10):800-5. doi: 10.1136/thx.2005.046797. Epub 2005 Jul 29.

  PMID: 16055611 BACKGROUND

• Matulis G, Juni P, Villiger PM, Gadola SD. Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon gamma assay. Ann Rheum Dis. 2008 Jan;67(1):84-90. doi: 10.1136/ard.2007.070789. Epub 2007 Jul 20.

  PMID: 17644549 BACKGROUND

• Takahashi H, Shigehara K, Yamamoto M, Suzuki C, Naishiro Y, Tamura Y, Hirohashi Y, Satoh N, Shijubo N, Shinomura Y, Imai K. Interferon gamma assay for detecting latent tuberculosis infection in rheumatoid arthritis patients during infliximab administration. Rheumatol Int. 2007 Oct;27(12):1143-8. doi: 10.1007/s00296-007-0361-2. Epub 2007 May 15.

  PMID: 17503048 BACKGROUND

• Ponce de Leon D, Acevedo-Vasquez E, Sanchez-Torres A, Cucho M, Alfaro J, Perich R, Pastor C, Harrison J, Sanchez-Schwartz C. Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis. Ann Rheum Dis. 2005 Sep;64(9):1360-1. doi: 10.1136/ard.2004.029041.

  PMID: 16100342 BACKGROUND

• D. Mines, Y. Gu, Q. Liu, L.N. Horne, M.J. Harrison. Global Safety Surveillance and Epidemiology. Wyeth Research, Collegeville, United States. [2008][OP-0138] Risk of Active Tuberculosis (TB) Among Biologic-Naïve RA Patients Retrospective Cohor Study in a US Claims Database. Ann Rheum Dis 2008;67(Suppl II):91.

  BACKGROUND

• Chen DY, Shen GH, Hsieh TY, Hsieh CW, Lan JL. Effectiveness of the combination of a whole-blood interferon-gamma assay and the tuberculin skin test in detecting latent tuberculosis infection in rheumatoid arthritis patients receiving adalimumab therapy. Arthritis Rheum. 2008 Jun 15;59(6):800-6. doi: 10.1002/art.23705.

  PMID: 18512714 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid; Tuberculosis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Adam T Armstrong, DO

  Rheumatology Fellow - Walter Reed Army Medical Center

  PRINCIPAL INVESTIGATOR

• Robert O Holmes, DO

  National Naval Medical Center

  STUDY CHAIR

Central Study Contacts

Robert O Holmes, DO

CONTACT

202-782-6735; robertoholmes@hotmail.com

Adam T Armstrong, DO

CONTACT

202-782-6734; david.t.armstrong@us.army.mil

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: FED

Study Record Dates

• First Submitted: May 13, 2009
• First Posted: June 22, 2009
• Study Start: May 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: June 1, 2011
• Last Updated: December 14, 2009

Record last verified: 2009-06

Locations

US (1)