ESAT6/CFP10 Skin Testing for TB Infection in Rheumatologic Patients

The Use of a Novel ESAT6/CFP10 Skin Test in Diagnosis of Latent Tuberculosis Infection Among Rheumatologic Patients

The aim of the study is to pilot the application of a novel ESAT6/CFP10 (C-TST) skin test in rheumatologic disease patients prior to initiation of treatment with biologic and/or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD). This is a prospective observational study involving the recruitment of patients with rheumatologic diseases who are planned for initiation of b/tsDMARD. Eligible patients would undergo skin testing by the Mantoux technique with purified protein derivative (PPD) RT23 on one forearm and C-TST on the other, alongside routine blood sampling for Interferon-Gamma Release Assay. The skin test results would be read within 48-72 hours afterwards. Treatment of TB infection would be provided in accordance with current clinical guidelines, followed by regular clinical monitoring for 2 years. Analyses involve performance evaluation of C-TST, and decision-analytical modelling incorporating multiple Markov process to evaluate the impact of management by LTBI testing methods on clinical outcomes and health care costs.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis (TB)
• Intervention / Treatment: Diagnostic test: ESAT6/CFP10 skin test

Detailed Description

Objective. The aim of the study is to pilot the application of a novel ESAT6/CFP10 (C-TST) skin test in rheumatologic disease patients prior to initiation of treatment with biologic and/or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD), with the objectives of determining its performance and the cost-effectiveness of clinical management for latent tuberculosis infection (LTBI).

Design. A prospective observational study

Setting. Rheumatology Specialist clinic services in Hong Kong

Methods. This study involves the recruitment of patients with rheumatologic diseases who are planned for initiation of b/tsDMARD. Eligible patients would undergo skin testing by the Mantoux technique with intradermal injection of 2U purified protein derivative (PPD) RT23 on one forearm and 5U of C-TST on the other, alongside routine blood sampling for Interferon-Gamma Release Assay (IGRA) with QuantiFERON-TB Gold. The skin test results would be read within 48-72 hours afterwards. Treatment of LTBI would be provided in accordance with current clinical guidelines, followed by regular clinical monitoring for 2 years. Analyses involve performance evaluation of C-TST, and decision-analytical modelling incorporating multiple Markov process to evaluate the impact of management by LTBI testing methods on clinical outcomes and health care costs.

Main outcome measures. Concordance between different tests for LTBI by Kappa measure; sensitivity and specificity of C-TST test estimated with current standard; proportion of new TB cases averted, discounted QALYG and ICER.

Anticipated outcome. The study would provide preliminary evidence regarding the diagnostic performance of C-TST, and impact of its utilisation for treatment decision for rheumatologic diseases patients in the prevention of active tuberculosis diseases.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Shui Shan Lee, MD; Phone Number: 852 22528812; Email: sslee@cuhk.edu.hk
• Study Contact Backup: Name: Ho So, FRCP; Phone Number: 852 3505 3139; Email: hoso@cuhk.edu.hk

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China, 0000
      • Recruiting
      • S.H. Ho Research Centre for Infectious Diseases
      • Contact: Shui Shan Lee, MD; Phone Number: 852-61703177; Email: sslee.ss@gmail.com
      • Contact: Ho So, FRCP; Phone Number: 852-35053139
• Hong Kong
  • Hong Kong
    • Shatin, Hong Kong, Hong Kong, 0000
      • Not yet recruiting
      • S.H. Ho Research Centre for Infectious Diseases
      • Contact: Shui Shan Lee, MD; Phone Number: 852 22528812; Email: sslee@cuhk.edu.hk
      • Contact: Ho So, FRCP; Phone Number: 852 3505 3139; Email: hoso@cuhk.edu.hk
      • Principal Investigator: Shui Shan Lee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Rheumatology patients followed up at the Specialist Services of regional hospitals in New Territories East Cluster in Hong Kong (Prince of Wales Hospital, Alice Ho Miu Ling Nethersole Hospital and North District Hospital)

Description

Inclusion Criteria:

1. adult of age ≥ 18 and up to 65 years;
2. diagnosis of at least one classified rheumatologic disease; and
3. being planned to receive b/tsDMARDs therapy,
4. can communicate in Chinese and/or English.

Exclusion Criteria:

• diagnosis of active TB diseases,
• currently receiving TB or LTBI treatment;
• concurrent mental illnesses;
• prisoners.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

study group; Adult patients with diagnosed rheumatologic diseases scheduled to receive b/tsDMARDs therapy

Diagnostic test: ESAT6/CFP10 skin test; Each recruited participant would be offered standard tuberculin skin test (TST) and ESAT6/CFP10 (C-TST) skin test on the same day or setting of clinical visit. TST and C-TST would be performed by the Mantoux technique with intradermal injection of 2U purified protein derivative-RT23 on one forearm and 5U (1.0µg/0.1 ml) of recombinant fusion protein ESAT6-CFP10 on the other forearm respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-TST reading	Concordance between C-TST and standard TST	from enrolment to reading test result at 48-72 hours
C-TST reading	Concordance between C-TST and IGRA test result	from enrolment to reading test result at 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion with TB disease	Proportion of patients by test results who developed TB disease	from enrolment to last followup at 2 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Study Director: David SC Hui, MD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): January 28, 2025

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: tuberculosis; skin testing; ESAT6/CFP10; rheumatology patients
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: HMRF23220212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access of individual level data at individual level is restricted for protection of privacy, as stipulated in the institutional approval

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No