By Sarah Rinehart, PharmD, BCACP
Patients with inflammatory bowel disease (IBD) are often treated with biologics or small molecules, including tumor necrosis factor (TNF)–α antagonists and corticosteroids.(1,2) Patients on these regimens with latent tuberculosis infection (LTBI) are at risk for reactivation of Mycobacterium tuberculosis to active tuberculosis (TB) disease.(3) Screening for LTBI using either TB blood tests (Interferon Gamma Release Assays [IGRAs] including QuantiFERON TB Gold and T.SPOT.TB) or tuberculin skin test (TST) should therefore be a routine part of workup prior to initiation of medication and monitored annually as a standard of practice.(4) Our clinic utilizes TB blood tests due to the high number of patients from other countries where the Bacille Calmette-Guérin vaccine is common, as well as follow-up challenges with reading the TST. If a TB test returns positive, active TB must be ruled out through a chest radiograph and assessment for symptoms suggestive of TB disease.(5) Early screening allows more time for a patient to complete a regimen of LTBI treatment, if indicated. Regrettably, screening does not often occur until a patient requires high-risk medications. The successful completion of this urgent LTBI treatment is often delayed due to barriers, such as appointment scheduling with a treating provider, understanding complex medication regimens, and non-adherence due to pill burden and refills to fulfill the entire prescribed treatment course.
In our interdisciplinary IBD clinic, we aim to screen most patients for LTBI as part of the initial diagnostic process. If a patient is diagnosed with LTBI and IBD, they are referred to the clinical pharmacist for expedition of LTBI medication (see figure 1 for important considerations). The Centers for Disease Control and Prevention (CDC) preferentially recommends rifamycin-based short course LTBI treatment regimens such as three months of once-weekly isoniazid plus rifapentine (3HP), four months of daily rifampin (4R), or three months of daily isoniazid plus rifampin (3HR) over isoniazid monotherapy (6H or 9H with duration 6- or 9-month, respectively).(6) Treatment regimens range from 12 to 270 total doses required, and due to the formulation of tablets and weight-based dosing, can include up to 10 tablets per dose. Of note, regimens containing isoniazid should also include addition of pyridoxine (vitamin B6), further increasing their complexity and pill burden.(7)
Since initiating this process in the IBD clinic, we have identified four patients with IBD requiring LTBI treatment and expanded this service to two patients identified in the hepatology clinic. All but one patient selected 4R as the treatment regimen, as the regimen requires only two pills daily and has relatively less hepatoxicity risk. Two patients successfully completed the regimen without issues. One patient was diagnosed with LTBI on annual screening while on TNF therapy, but then was incarcerated 2.5 months into his regimen, and LTBI and TNF–α therapies were withheld for 5 months. Due to the gap and based on limited data, 4R was re-started upon release, and the patient completed four consecutive months of treatment with TNF–α restarted one month into 4R.(8-11) Another patient with LTBI on TNF–α therapy transferred to our clinic, and upon contacting the pharmacy for refill history, it was discovered that the patient did not complete the entire 4R course last year. This was unbeknownst to the patient. 4R was recently re-initiated with a plan to hold TNF–α until one month into 4R. The two hepatology patients were much more complex with various overlapping disease states (hepatitis C virus [HCV] and psoriasis; rheumatoid arthritis and metabolic dysfunction-associated fatty liver disease), and treatment options were complicated by elevated liver enzymes and drug interactions. The pharmacist was able to successfully guide the patient with HCV through sequential treatment for LTBI and HCV while managing drug interactions, and the patient’s psoriasis is now stable on a biologic. The pharmacist successfully guided the other patient through resolution of elevated liver enzymes through weight management with a glucagon-like peptide-1 receptor agonist, but then the patient was lost to follow-up prior to initiation of LTBI therapy.
Conclusion
Many other patient populations are also at risk of LTBI reactivation, including patients living with HIV and diabetes mellitus, as well as those on biologics/small molecules or steroids for other indications under specialties such as rheumatology or dermatology. Primary care providers and pharmacists within various clinics are primed to screen for and successfully treat LTBI.(12-17)
Figure 1: Important Considerations for LTBI Treatment by PharmD
Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter Y, Singh S. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology 2020;158:1450–1461.
Feuerstein JD, Ho EY, Shmidt E, Singh H, Falck-Ytter Y, Sultan S, Terdiman JP. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn’s Disease. Gastroenterology 2021;160:2496–2508.
Kiazyk S, Ball TB. Latent tuberculosis infection: An overview. Can Commun Dis Rep. 2017 Mar 2;43(3-4):62-66. doi: 10.14745/ccdr.v43i34a01. PMID: 29770066; PMCID: PMC5764738.
US Preventive Services Task Force. Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2023;329(17):1487–1494.
Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clinical Infectious Diseases. 2017;64(2):e1–e33.
Sterling TR, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep 2020;69(No. RR-1):1–11. DOI: http://dx.doi.org/10.15585/mmwr.rr6901a1.
Snider DE Jr. Pyridoxine supplementation during isoniazid therapy. Tubercle. 1980 Dec;61(4):191-6. doi: 10.1016/0041-3879(80)90038-0. PMID: 6269259.
California Department of Public Health. Rifampin for Latent TB Infection (LTBI) Treatment [Internet]. California Department of Public Health (CDPH) Tuberculosis Control Branch (TBCB) and California Tuberculosis (TB) Controllers Association (CTCA) Joint Guidelines and Fact Sheets; 2018 [cited 2024 Sep 5]. Available from: https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/TBCB-RIF-for-LTBI-Fact-Sheet.pdf.
Martínez-López A, Rodriguez-Granger J, Ruiz-Villaverde R. Screening for Latent Tuberculosis in the Patient With Moderate to Severe Psoriasis Who Is a Candidate for Systemic and/or Biologic Therapy. Actas Dermo-Sifiliográficas (English Edition). 2016;107(3): 207-214.
Puig L, Bordas X, Carrascosa JM, et al. Consensus Document on the Evaluation and Treatment of Moderate to Severe Psoriasis. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology. Actas Dermo-Sifiliográficas (English Edition). 2009;100(4): 277-288.
Yamana H, Iba A, Tomio J, Ono S, Jo T, Yasunaga H. Treatment of latent tuberculosis infection in patients receiving biologic agents. Journal of Infection and Chemotherapy. 2021;27(2):243-249.
Centers for Disease Control and Prevention (CDC). Latent Tuberculosis Infection: A Guide for Primary Health Care Providers [Internet]. Atlanta (GA): U.S. Department of Health and Human Services; 2013 [cited 2024 Sep 5]. Available from: https://www.cdc.gov/tb/media/pdfs/Latent-TB-Infection-A-Guide-for-Primary-Health-Care-Providers.pdf.
Jakeman B, Logothetis SJ, Roberts MH, et al. Addressing Latent Tuberculosis Infection Treatment Through a Collaborative Care Model With Community Pharmacies and a Health Department. Prev Chronic Dis 2020;17:190-263.
Tavitian SM, Spalek VH, Bailey RP. A pharmacist-managed clinic for treatment of latent tuberculosis infection in health care workers. Am J Health Syst Pharm 2003;60(18):1856–61.
Hess K, Goad J, Wu J, Johnson K. Isoniazid completion rates for latent tuberculosis infection among college students managed by a community pharmacist. J Am Coll Health 2009;57(5):553–5.
Last JP, Kozakiewicz JM. Development of a pharmacist-managed latent tuberculosis clinic. Am J Health Syst Pharm 2009;66(17):1522–3.
Carter KL, Gabrellas AD, Shah S, Garland JM. Improved latent tuberculosis therapy completion rates in refugee patients through use of a clinical pharmacist. Int J Tuberc Lung Dis 2017;21(4):432–7.
Sarah Rinehart, PharmD, BCACP
Clinical Pharmacy Specialist
Gastroenterology and Hepatology Clinics
Department of Pharmacotherapy and Pharmacy Services
University Health System – Robert B. Green Campus
San Antonio, TX
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