LTBI Treatment and Anti TNF alpha Therapy Julie Higashi, MD PhD Director, TB Control Section San Francisco Department of Public Health TNF alpha is important for the immune response against TB Macrophages produce TNF alpha to stimulate T cells T cells produce TNF alpha to stimulate macrophages to kill tuberculosis (TB) TNF alpha and other factors induce recruitment and organized accumulation into granuloma TNF alpha blockade Granuloma breakdown, dissemination of M.tb Ehlers, et al., Clin Infect Dis, 2005 Clinical Case Woman in her 60s with mild moderate rheumatoid arthritis; candidate for anti TNF alpha therapy QuantiFERON test (QFT) positive, chest x ray (CXR) apical fibrosis LatentTB infection (LTBI) treatment with Isoniazid (INH) Rifampin (RIF) Rifabutin (RFB) Moxifloxacin (MOXI) All complicated by recurrent pruritus, no rash. Patient self discontinued multiple regimens after only a few days to weeks of treatment.
What should happen next? Proceed with anti TNF alpha therapy Rechallenge LTBI treatment Discuss options with rheumatologist Readdress treatment plan with patient What is the risk for progression to active TB on anti TNF alpha therapy? Winthrop et al., Ann Rheum Dis, 202 What is the risk for progression to active TB on anti TNF alpha therapy? Winthrop et al., Ann Rheum Dis, 202 2
Is preventive treatment for LTBI effective prior to anti TNF treatment? Patients in Spanish National Registry on anti- TNF alpha therapy treated 2002-2006 598 TST performed? 605 No Yes 4593 3573 02 Boosted TST? INH treatment 8 377 No Yes 296 Yes 950 No 56 CXR performed? 2022 68 INH treatment No Yes Yes 56 3 40 982 No 2 Chest xray compatible with past TB 634 74 INH treatment Yes 48 Gomez-Reino, et al., Arth Rheum, 2007 No 26 Effectiveness of Compliance with TB Screening and Treatment 20 Incidence rate ratio of active TB in rheumatoid arthritis population 5 0 5 0 Before 00% compliance <00% compliant vs. General Population 9.8 3 Gomez-Reino, et al., Arth Rheum, 2007 LTBI Screening and Anti TNF Alpha Therapy Screening Risk assessment (high risk vs. low risk for exposure) Screening test always Screening test and CXR if high risk for exposure to TB LTBI treatment appropriate for anyone who has history of high risk exposure regardless of screening test results Solovic, et al., Eur Resp J, 200 3
LTBI Treatment and Anti TNF Alpha Therapy Country LTBI Rx LTBI regimen Time delay before anti TNF France TST >0mm, Hx rx before 970, rx <6 m, CXR 2RZ, 3HR, 9H > 3 weeks lesions > cm 3 Germany IGRA+, abnl CXR suggestive TB without rx, 9H, 4R 2 months history of exposure Ireland TST >0mm, >5mm if immunosuppressed 9H, 4R, 4HR As long as possible after starting Rx Portugal TST >5mm, consider rx in TST neg 9H month Spain TST >5mm, abnl CXR suggestive TB without rx, hx exposure 9H month, but consider days after or concurrent Switzerland IGRA+, abnl CXR suggestive TB without rx, hx 9H, 4R month exposure UK TST >5mm, abnl CXR suggestive TB without rx, hx exposure, 6H, 3HR Abnl cxr complete rx, nl cxr, immunocompromised start concurrent USA TST+ (same cutoffs as gen pop), TST, clinical 9H Preferably complete rx or epi risks TB NET IGRA+, TST >0mm 9 2H, 3HR > 4 weeks How long do you recommend treatment for LTBI before starting anti TNF therapy? Concurrent initiation of LTBI and anti TNF alpha At least one week of LTBI treatment At least one month LTBI treatment Completion of LTBI treatment Rescreening/Retreatment Rescreening (if has diagnosis of LTBI) Yearly symptom review + CXR if never treated or symptomatic If new exposure to Mtb Retreatment for Exposure If close contact to active case, e.g., smear positive or culture positive index, would initiate treatment for LTBI Decision to complete full course of treatment rests on infectiousness of index, immune status of patient, low threshhold to complete treatment 4
Clinical Case Woman in her 60s with mild moderate rheumatoid arthritis; candidate for anti TNF alpha therapy Initiation of anti TNF alpha therapy was not urgentafter discussion with rheumatologist Recommended deferring anti TNF alpha therapy until she was ready for LTBI treatment 3HP would be our best option 5