The use of methotrexate is linked to increased risks of tuberculosis


Tuberculosis screening among patients receiving methotrexate in high risk areas is a highly unmet need in public health.

In a new evaluation presented at the American College of Rheumatology (ACR) Convergence 2020, researchers from North America reported that methotrexate, a key element in the treatment of rheumatic diseases and a factor in disrupting cell-mediated immunity, was associated with major cases of regional tuberculosis.

The systematically reviewed results could help experts identify rheumatic patients in key regions with higher TB epidemic risks and help them make more informed prescribing decisions based on those risks.

Investigators, led by Carol Hitchon, MD, Associate Professor of Medicine at the University of Manitoba, sought to provide a comprehensive review of the available data on associations between rates of tuberculosis and weekly prescribed methotrexate <30 mg.

As Hitchon noted, tuberculosis is endemic in all regions of the world, including Africa, and guidance is needed to understand the role of compromising therapies, including methotrexate.

“Existing guidelines do not address the possible increased risk of tuberculosis in these areas,” he said in a statement. “As a step in developing recommendations for the use of methotrexate for these areas, we wanted to review the literature on methotrexate use and the incidence and re-diagnosis of TB in people taking methotrexate.”

The systematic review by Hitchon and colleagues included the evaluation of 4 different databases for related studies involving methotrexate and tuberculosis, published between January 1990 and May 2018. Their search included 4707 reports, which were independently selected by 2 reviewers for the diagnosis of tuberculosis in patients taking methotrexate. . They extracted data on the incidence of TB (new diagnosis vs latent reactivation) and patient outcomes.

Their final evaluation included 31 studies that met the criteria: 8 cohort, 7 case-control, 1 clinical study, and 15 case reports / series. Just over a quarter (27%) reported data from low to moderate human development index countries. Most case-control studies demonstrated a modest increased risk of tuberculosis with methotrexate, while 5 cohorts reported TB incidence rates in rheumatic diseases ranging from 102 to 367.9 per 100,000 patient-years, generally indicating rates higher than the comparison populations.

A couple of cohort analyzes of methotrexate in rheumatoid arthritis reported a cumulative incidence of tuberculosis in Maldova – 12 cases for 44 patients – and in China – 9 cases for 114 patients.

“When reported, extra-pulmonary tuberculosis rates were higher than the general population comparison rates,” the researchers wrote.

Although 2 other case series, 2 cohorts and a clinical study indicated that isoniazid-related hepatotoxicity and neutropenia were more frequent among patients treated with methotrexate, the researchers confirmed that these were generally reversible effects.

Hitchon explained that the findings have significant implications for prescribing doctors around the world, especially those in regions with high rates of TB and for those treating travelers returning from those regions.

“Reactivation of tuberculosis should be considered for anyone with possible previous exposure to tuberculosis,” he said. “This is especially true for patients who are also taking steroids. The overlapping toxicity profiles, such as liver toxicity, for methotrexate with treatments for tuberculosis indicate the need for careful monitoring. “

The team concluded that although the high quality of the association was minimal, their review confirmed that tuberculosis screening and clinical surveillance are very necessary for patients in endemic areas taking methotrexate, “particularly with co – administration of corticosteroids or other immunosuppressants “.

The study, “Safety of low-dose methotrexate (MTX) and tuberculosis (TB),” was presented at ACR 2020.


Source link