Dataset Information

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

ABSTRACT:

Objective

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).

Methods

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-? release assay, and/or 3) linear/reticular fibrotic lesions on chest radiographs. Primary outcome was 1-year incidence of TB in each group.

Results

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).

Conclusion

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.

SUBMITTER: Park JW

PROVIDER: S-EPMC7774985 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

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

Park Jun Won JW Curtis Jeffrey R JR Lee Hajeong H Lee Jung-Kyu JK Song Yeong Wook YW Lee Eun Bong EB

PloS one 20201231 12

<h4>Objective</h4>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).<h4>Methods</h4>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 ( ...[more]

PMID: 33382731

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Project description:BackgroundThe dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period.MethodsWe randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette-Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization.ResultsAntiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P=0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P=0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups.ConclusionsPrimary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children. (Funded by the National Institutes of Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.).

Project description:BackgroundTuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates.MethodsWe conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25.ResultsA total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, -0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P = 0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001).ConclusionsA 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.).

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Dataset Information

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

Objective

Methods

Results

Conclusion

Publications

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

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