Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


A Comprehensive Tuberculosis Screening Program in Patients with Inflammatory Arthritis Treated with Golimumab, a Human Anti-TNF Antibody, in Phase 3 Clinical Trials.

Hsia4,  Elizabeth C., Cush1,  John J., Matteson5,  Eric L., Beutler2,  Anna, Doyle4,  Mittie K., Hsu3,  Benjamin L., Rahman4,  Mahboob U.

Baylor Research Institute, Dallas, TX
Centocor Research and Development, Inc., Collegeville, PA
Centocor Research and Development, Inc./Univ. of Pennsylvania School of Medicine, Wynnewood, PA
Centocor Research and Development, Inc./Univ. of Pennsylvania School of Medicine, Malvern, PA
Mayo Clinic, Rochester, MN

Background:

Reactivation of Mycobacterium tuberculosis infection is a major complication in patients (pts) with inflammatory diseases treated with anti-tumor necrosis factor (TNF) agents. Screening and appropriate treatment (tx) for latent TB infection (LTBI) before initiation of TNF blockers, as well as prompt diagnosis (dx) of active TB cases, can decrease morbidity and mortality.

Objectives:

To summarize active TB case reports by wk52 across 5 SC GLM studies (3 RA, 1 PsA, and 1 AS).

Methods:

Pts enrolled from North & South America, Europe (Western + Eastern), Australia/New Zealand, and Asia. TB eligibility criteria included: no history of latent/active TB; no signs/symptoms of active TB; negative (-) tuberculin skin test (TST) and QuantiFERON®-TB Gold test In-Tube (QFT) or if newly identified +TST or+QFT with active TB ruled out, had tx for LTBI initiated before or at 1st dose. TST done using Mantoux method and + per local guidelines for immunosuppressed or if >=5mm if no guidelines. All pts had chest x-ray (CXR) <= 3 months before 1st dose. Targeted questions for early dx of active TB were asked q4wks.

Results:

Among 2294 randomized pts, 316 (13.8%) had either TST+ or QFT+ screening test and required tx for LTBI. Through wk52, none of those tx for LTBI developed active TB while on GLM. Active TB occurred in 5 pts by wk52 (Table). Cases were in countries with high background rates of TB. 2 cases occurred by wk24 and were more consistent with reactivation. There were no deaths due to TB.

Conclusion:

Despite 2 screening tests and CXR, to detect LTBI, there were still cases of TB reactivation. However, given that many enrolled pts resided in TB endemic areas, the number of active TB cases may have been higher with a less conservative TB screening strategy. Even if TB screening tests are -, clinicians should remain vigilant for development of active TB after initiation of TNF blockers, as prompt dx and tx can lead to improved outcomes.

  Case of TB Across Golimumab Phase 3 Studies 
StudyDxScreening TB test results/BCG statusTB test results at time of Dx# Doses of GLMDemographics/GLM DoseOutcome
RA, MTX naïveBone TB of spineQFT-TST-(0 mm) CXR wnl BCG+(at birth)QFT+ TST-CXR wnl364-y/o WF Ukraine DD = 7.4 yrs GLM 50 mgResidual disability due to paresis
 TB pleurisyQFT- TST-(0mm) CXR wnl BCG-QFT-TST-(0mm) CXR abnl1165-y/o AF Philippines DD = 1.4 yrs GLM 100mgRec
 Pulm TBQFT-TST-(5mm) CXR ILD BCG-QFT indeterminate TST+(10mm) CXR same as screening767-y/o AF Philippines DD = 0.9 yrs GLM 50 mgRec
RA despite MTXTB pleurisyQFT-TST-(15m) CXR wnl BCG+(age 12)QFT+TST+(20mm) CXR large pleural effusion638-y/o AF Taiwan DD = 13.7yrs GLM 50mgRec
AS despite conventional txPulm TBQFT-TST-(3mm) CXR wnl BCG+ (age 4)QFT+ TST+ (17 mm) CXR LUL infiltrate1025-y/o AM South Korea DD = 2 yrs GLM 100 mgRec
Pulm = pulmonary; BCC = Bacillus Calmette-Guérin; DD = disease duration; wnl = within normal limits; abnl=abnormal, y/o = year-old; yr(s) = year(s); LUL = left upper lobe; F = female; M = male; A = Asian; W = white; ILD = interstitial lung disease; Rec = recovered

To cite this abstract, please use the following information:
Hsia, Elizabeth C., Cush, John J., Matteson, Eric L., Beutler, Anna, Doyle, Mittie K., Hsu, Benjamin L., et al; A Comprehensive Tuberculosis Screening Program in Patients with Inflammatory Arthritis Treated with Golimumab, a Human Anti-TNF Antibody, in Phase 3 Clinical Trials. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :890
DOI: 10.1002/art.28658

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