Safety and Side Effects of Rifampin versus Isoniazid in Children
Safety and Side Effects of Rifampin versus Isoniazid in Children
Data
2018
Autores
Diallo, T.
Adjobimey, M.
Ruslami, R.
Trajman, A.
Sow, O.
Baah, J. Obeng
Marks, G.B.
Long, R.
Elwood, K.
Zielinski, D.
Journal Title
Journal ISSN
Volume Title
Publisher
New England Journal of Medicine
Resumo
BACKGROUND
The treatment of latent infection with Mycobacterium tuberculosis is important in
children because of their vulnerability to life-threatening forms of tuberculosis
disease. The current standard treatment — 9 months of isoniazid — has been
associated with poor adherence and toxic effects, which have hampered the ef-
fectiveness of the drug. In adults, treatment with 4 months of rifampin has been
shown to be safer and to have higher completion rates than 9 months of isoniazid.
METHODS
In this multicenter, open-label trial, we randomly assigned 844 children (<18 years
of age) with latent M. tuberculosis infection to receive either 4 months of rifampin or
9 months of isoniazid. The primary outcome was adverse events of grade 1 to 5 that
resulted in the permanent discontinuation of a trial drug. Secondary outcomes
were treatment adherence, side-effect profile, and efficacy. Independent review
panels whose members were unaware of trial-group assignments adjudicated all
adverse events and progression to active tuberculosis.
RESULTS
Of the children who underwent randomization, 829 were eligible for inclusion in
the modified intention-to-treat analysis. A total of 360 of 422 children (85.3%) in
the rifampin group completed per-protocol therapy, as compared with 311 of 407
(76.4%) in the isoniazid group (adjusted difference in the rates of treatment
completion, 13.4 percentage points; 95% confidence interval [CI], 7.5 to 19.3).
There were no significant between-group differences in the rates of adverse events,
with fewer than 5% of the children in the combined groups with grade 1 or 2 ad-
verse events that were deemed to be possibly related to a trial drug. Active tuber-
culosis, including 1 case with resistance to isoniazid, was diagnosed in 2 children
in the isoniazid group during 542 person-years of follow-up, as compared with no
cases in the rifampin group during 562 person-years (rate difference, −0.37 cases
per 100 person-years; 95% CI, −0.88 to 0.14).
CONCLUSIONS
Among children under the age of 18 years, treatment with 4 months of rifampin
had similar rates of safety and efficacy but a better rate of adherence than
9 months of treatment with isoniazid. (Funded by the Canadian Institutes of
Health Research and Conselho Nacional de Pesquisa; ClinicalTrials.gov number,
NCT00170209.).
Description
Palavras-chave
Adolescent, Antibiotics, Antitubercular / administration & dosage*, Antibiotics, Antitubercular / adverse effects*, Child, Child, Preschool, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Infant, Intention to Treat Analysis, Isoniazid / administration & dosage*, Isoniazid / adverse effects*, Latent Tuberculosis / drug therapy*, Male, Medication Adherence, Patient Safety, Rifampin / administration & dosage*, Rifampin / adverse effects*, Treatment Outcome.
Citação
Diallo T, Adjobimey M, Ruslami R, Trajman A, Sow O, Obeng Baah J, Marks GB, Long R, Elwood K, Zielinski D, Gninafon M, Wulandari DA, Apriani L, Valiquette C, Fregonese F, Hornby K, Li PZ, Hill PC, Schwartzman K, Benedetti A, Menzies D. Safety and Side Effects of Rifampin versus Isoniazid in Children. N Engl J Med. 2018 Aug 2;379(5):454-463. doi: 10.1056/NEJMoa1714284.