Effectiveness of Recommendations to Prevent Reactivation of Latent Tuberculosis Infection in Patients Treated With Tumor Necrosis Factor Antagonists Loreto Carmona, Juan J. Go´mez-Reino, Vicente Rodrı´guez-Valverde, Dolores Montero, Eliseo Pascual-Go´mez, Emilio Martin Mola, Luis Carren˜o, and Manuel Figueroa, on behalf of the BIOBADASER Group ARTHRITIS & RHEUMATISM Vol. 52, No. 6, June 2005

Background tumor necrosis factor (TNF) antagonists Rheumatoid arthritis (RA) Crohn’s disease Active tuberculosis reactivation of latent TB infection tumor necrosis factor (TNF) antagonists Spanish Society of Rheumatology (SER) - Database on Biologic Products, or BIOBADASER - rheumatic condition treated with TNF antagonists. - 4 years, >4,000 patients from 95 hospitals

Background Recommendations for the management of latent TB infection in those patients receiving TNF antagonists (March 2002) 1) history of untreated or partially treated TB, or exposure to an active case of TB 2) chest radiograph showing residual changes indicative of prior TB infection 3) reaction of 5 mm in diameter on the purified protein derivative of tuberculin skin test (TST) or on the 2-step TST procedure with an interval of 7–10 days between steps should be treated for 9 months with isoniazid (INH)

PATIENTS AND METHODS BIOBADASER - established in February 2000 - purpose ; long-term safety of biologic response-modifiers in patients with rheumatic diseases - All hospital and community-based rheumatology units - Data ; 1) identification of center, department, or unit, including contact person details 2) data on patients, including sex, date of birth, diagnosis, and date of diagnosis 3) data on treatment, including type of treatment, start and discontinuation dates, and reason for treatment discontinuation - March 1, 2002 ; TST results, CXR finding, type of therapy

PATIENTS AND METHODS EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) study - TB rates in patients with RA who have not been treated with TNF antagonists - assembled in 1999 by random sampling - 34 established rheumatology units - 788 patients with RA active TB Mycobacterium tuberculosis was isolated in any biologic specimen from an individual patient, in conjunction with an appropriate clinical picture.

Results

infliximab-treated patients Infliximab (6,328 patient-years) Etanercept (1,375 patient-years) Adalimumab (122 patient-years) 7825 infliximab-treated patients (324 pt)

78% 83%

Abnormally high levels of aminotransferase ; 25 patients 22 receiving infliximab 3 receiving etanercept ; No hospitalization as consequence of hepatic failure.

Conclusion patients receiving TNF antagonists TST result ≥ 5 mm chest radiography finding suggestive of previous TB preventing reactivation of latent TB infection 9 months of INH therapy

양성 (10mm≤) 음성 (<10mm) 흉부 엑스선, 임상적 평가 흉부 엑스선, 임상적 평가 흉부 엑스선 정상 그림1. 잠복결핵 대상자 선정 흐름표 양성 (10mm≤) 음성 (<10mm) 흉부 엑스선, 임상적 평가 흉부 엑스선, 임상적 평가 흉부 엑스선 정상 흉부 엑스선 정상 흉부 엑스선 완치 흔적 임상적 증상흉부 엑스선 이상 소견 최근 3개월 결핵 접촉력 과거 치료력 무/부적절 과거 적절한 치료 없음 있음 현증 결핵 평가 조치 필요 없음 잠복결핵 치료 조치 필요 없음