Patients currently taking a glucocorticoid have nearly a fivefold increased risk of developing tuberculosis that is independent of other risk factors.
“Our results suggest that glucocorticoid use is associated with a substantially increased risk of developing tuberculosis and that the risk increases with increasing daily dose,” said Susan S. Jick, Sc.D., of Boston University, and her colleagues.
Although chronic corticosteroid use is common among patients with rheumatic diseases, the number of such patients in the study population was too small to say definitely whether use of corticosteroids specifically for arthritis and other rheumatic diseases was associated with an increased risk for TB.
Low body mass index (BMI), diabetes, current smoking, and obstructive pulmonary disorders were also determined to be important risk factors for tuberculosis in a review of 497 new cases of tuberculosis and 1,966 matched controls during the period 1990–2001 (Arthritis Rheum. 2006;55:19–26).
The researchers based their study on data available from the U.K.-based General Practice Research Database. Patients were included if they had a first-time diagnosis of tuberculosis followed by treatment with at least three different antituberculosis medications and if treatment lasted at least 6 months. As many as four control subjects were matched to each patient based on age, gender, the practice attended, and the patient's index date along with the control's visit to the practice that corresponded in time to the patient's index visit.
Assessment of glucocorticoid use was based on prescription data. Patients were classified as currently exposed if they had received a prescription for any oral glucocorticoid and if the supply had lasted until within 120 days prior to the index date. Recent exposure was defined as use that ended 121–180 days before the index date. All other use more than 180 days prior was considered past use.
The researchers also assessed current exposure to antirheumatic drugs or immunosuppressants and the presence of pulmonary disorders, rheumatic disorders, inflammatory bowel diseases, dermatitis, silicosis, renal failure, gastrectomy, and jejunoileal bypass surgery (diagnosed prior to the index date).
Patients currently using corticosteroids were 4.9 times more likely to develop tuberculosis than were nonusers, even after adjusting for the effects of BMI, smoking, disease-modifying antirheumatic drug use, and history of diabetes and pulmonary disease. The risk for tuberculosis remained elevated (OR 4.3) in patients who had recently stopped using corticosteroids.
First-time users were 3.2 times more likely to get tuberculosis than were never users. Patients with longer-term use, extending over two to nine consecutive prescriptions, saw their risk increase sevenfold.
The effect of corticosteroid use on risk for TB increased with increasing dose. The OR was 2.3 in people taking daily doses of prednisone equivalents less than 7.5 mg daily (physiologic) versus those taking supraphysiologic doses of 7.5 mg or more daily (OR 7.0, based on the highest daily dosage received by current users).
Both the American Thoracic Society and the Centers for Disease Control and Prevention agree that more than 15 mg/day of prednisone or its equivalent administered for 1 month or longer is a risk factor for tuberculosis. In light of this, the researchers evaluated the impact of daily dosage using this cutoff. The adjusted odds ratio was 2.8 for those using less than 15 mg of prednisone equivalents per day, while those using 15 mg of prednisone equivalents per day or more had an adjusted odds ratio of 7.7.
“We found that current smoking was associated with a 60% increased risk of tuberculosis. … Although this effect is relatively low, because smoking is prevalent in this study population 17% of all cases are attributable to smoking compared with only 8% of cases attributable to glucocorticoid use in this population,” the researchers said. Those with a BMI less than 20 kg/m
Prior pulmonary diagnoses were also associated with an increased risk of tuberculosis that was independent of other risk factors. A diagnosis of rheumatic disease and use of antirheumatic agents are purported to be risk factors for tuberculosis as well.
However, the number of patients taking antirheumatic drugs in this analysis was low—only 12 patients were currently exposed. Overall 17 participants (cases and controls) had rheumatoid arthritis, 1 had lupus, 12 had polymyalgia rheumatica, and 7 had arteritis. “Despite the large number of tuberculosis cases in this study, the prevalence of antirheumatic agent use was low … and therefore the independent effects for patients taking antirheumatic agents could not be reliably evaluated,” the researchers said.
In an accompanying editorial, Dr. Loreto Carmona observed that “the truth is that the report says little about the risk of TB in patients with rheumatic disease who are treated with glucocorticoids” (Arthritis Rheum. 2005;55:1–2). Dr. Carmona heads the research unit of the Spanish Foundation of Rheumatology in Madrid. It's unclear how much of the risk of tuberculosis is due to rheumatic diseases—for which corticoids are taken—and how much is due to the glucocorticoids.