Elsevier

Joint Bone Spine

Volume 69, Issue 2, March 2002, Pages 170-172
Joint Bone Spine

ORIGINAL ARTICLE
Recommendations about the prevention and management of tuberculosis in patients taking infliximab

https://doi.org/10.1016/S1297-319X(02)00387-1Get rights and content

Abstract

An unusually large number of cases of tuberculosis, often with miliary or dissemination, has been reported in patients taking infliximab for rheumatoid arthritis or Crohn’s disease. Recommendations have been issued in France regarding the definition of high-risk patients, the screening methods to be used in these patients, and possible prophylactic treatments. The present update is also intended to help physicians manage tuberculosis occurring before or during infliximab therapy.

Section snippets

Who is at risk?

The risk of tuberculosis is increased in patients with latent tuberculosis (or tuberculous infection) or with a high risk of tuberculous reactivation defined as:

  • a history of tuberculosis treated before 1970 or not treated for at least 6 months including at least 2 months on the rifampin-pyrizinamide combination;

  • in response to an intradermal tuberculin test done more than 10 years after the last BCG vaccination, a wheal larger than 10 mm in diameter or a blister, with no history of active

In patients with active tuberculosis (tuberculous disease)

Patients with a suspicion of active tuberculosis should undergo a full diagnostic workup for tuberculosis and should receive a full course of antituberculous treatment.

If tuberculosis is suspected or diagnosed, infliximab therapy must be postponed.

How should the risk of tuberculosis be evaluated?

Before starting infliximab therapy, the risk of latent or active tuberculosis should be evaluated in each patient by a detailed interview focusing on the following points: date of the last BCG vaccination, if received; results of previous intradermal tuberculin tests; history of contact with patients having tuberculosis (tuberculosis in family members, even during the patient’s childhood); whether the patient is from, or has stayed for long periods in, countries where tuberculosis is endemic;

Management of latent tuberculosis

Before starting infliximab therapy, antituberculous chemoprophylaxis should be initiated in all patients who have primary tuberculosis or a high risk of tuberculous reactivation.

Two regimens can be used for chemoprophylaxis:

  • Rifampin (Rifadine®) 10 mg/kg/d and pyrazinamide (Pirilène®) 20 mg/kg/d, each in a single daily dose, for 2 months. However, the efficacy of this regimen for prophylactic treatment has been validated only in HIV-infected patients.

  • Rifampin (Rifadine®) 10 mg/kg/d in a single

Management of active tuberculosis diagnosed before or during infliximab therapy

All patients should be informed of the need to seek medical advice should they experience signs or symptoms suggestive of tuberculosis (persistent cough, asthenia, weight loss, fever) during or within 6 months after discontinuation of infliximab therapy.

Patients with suspected tuberculosis should undergo the following investigations: tests for the tubercle bacillus on three consecutive days in sputum or gastric aspirates; intradermal tuberculin test; chest radiograph; and, if a parenchymal

Can infliximab therapy be resumed?

In the absence of prospective data, resumption of infliximab therapy is not recommended. If the clinical value of infliximab is considered major, the drug should be started no sooner than 2 months after the end of the antituberculous treatment. It is essential to make sure that there is no clinical or radiographic evidence of active tuberculosis and that tests for the tubercle bacillus are negative.

Current knowledge suggests that isoniazid alone or with rifampin should be given as long-term

Prescription of systemic or local glucocorticoid therapy in patients with tuberculosis under infliximab

There is no contraindication to intra-articular or systemic glucocorticoid therapy. Glucocorticoid therapy is recommended in patients with tuberculous miliary, meningitis, or pericarditis. Because rifampin accelerates the breakdown of glucocorticoids, the glucocorticoid dose should be increased by 40%.

Conclusions

These recommendations should substantially reduce the frequency and severity of tuberculosis occurring during infliximab therapy. However, many issues remain unsettled, and changes in these recommendations are likely to occur in the near future.

References (1)

  • J. Keane et al.

    Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent

    N Engl J M

    (2001)

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