Risk-benefit analysis of isoniazid monotherapy to prevent tuberculosis in patients with rheumatic diseases exposed to prolonged, high-dose glucocorticoids

• Published in: PloS one 2020-12, Vol.15 (12), p.e0244239
• Main Authors: Park, Jun Won, Curtis, Jeffrey R, Lee, Hajeong, Lee, Jung-Kyu, Song, Yeong Wook, Lee, Eun Bong
• Format: Article
• Language: English
• Subjects: Adult; Antitubercular Agents - therapeutic use; Care and treatment; Complications and side effects; Corticosteroids; Disease; Dosage and administration; Drug dosages; Female; Fibrosis; Glucocorticoids; Glucocorticoids - adverse effects; Health risks; Hepatitis; HIV; Hospitals; Human immunodeficiency virus; Humans; Immunization; Immunology; Infections; Interferon; Internal medicine; Isoniazid; Isoniazid - therapeutic use; Male; Medical schools; Medicine; Medicine and Health Sciences; Middle Aged; Patients; Physical Sciences; Polymerase chain reaction; Prednisone; Prevention; Prognosis; Prophylaxis; Radiographs; Radiography; Rheumatic diseases; Rheumatic Diseases - drug therapy; Rheumatic Diseases - pathology; Rheumatology; Risk analysis; Risk Assessment; Risk factors; Risk groups; Risk management; Side effects; Steroid hormones; Steroids; Subgroups; Testing; Tuberculosis; Tuberculosis - chemically induced; Tuberculosis - drug therapy; Tuberculosis - pathology; Tumor necrosis factor-TNF; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0244239

To investigate the incidence of tuberculosis (TB) in patients with rheumatic diseases receiving high-dose glucocorticoids and to evaluate the preventive effect of isoniazid (INH). This study included 1618 treatment episodes of prolonged (≥4 weeks), high-dose steroids (≥30mg/day of prednisone) in 1160 patients. Of these, INH was administered in 152 (9.4%) treatment episodes (INH group), while others received no prophylaxis (control group). The high-risk subgroup (n = 92) was defined as patients with 1) incomplete adherence to treatment of previous TB, 2) positive interferon-γ release assay, and/or 3) linear/reticular fibrotic lesions on chest radiographs. Primary outcome was 1-year incidence of TB in each group. During 1579.8 person-years, 21 cases of TB occurred. The high-risk subgroup showed a significantly higher TB incidence than the non-high-risk subgroup (Incidence rate ratio = 8.29). INH did not significantly affect the 1-year TB incidence in the whole population but numerically reduced it only in the high-risk subgroup [adjusted hazards ratio = 0.37 (95% CI, 0.002-5.10)]. The incidence of adverse drug reactions (ADRs) related to INH was 111.6 (89.3-137.9)/100 person-years, including one fatal occurrence of fulminant hepatitis. The number needed to treat (NNT) to prevent one case of TB was lower than the number needed to harm (NNH) for one case of severe ADR only in the high-risk subgroup (11 vs. 16). INH treatment to prevent TB might be effective in high-risk patients but has a risk of frequent ADRs, which limits its use in general practice in patients not at a high risk of developing TB.