American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 288, (2007)
© 2007 American Thoracic Society
Correspondence Anti–Tumor Necrosis Factor- in Asthma
To the Editor:
In their recent article on the effects of anti–tumor necrosis factor (TNF)- in asthma, Erin and colleagues report that infliximab reduces the number of asthma exacerbations in symptomatic patients with moderate asthma who are taking inhaled corticosteroids (1). Although I recognize the need for new asthma treatment modalities, I have serious problems with the use of anti–TNF- in this patient group as the drug can induce severe side effects.
The dose of inhaled corticosteroids used was not high (in placebo and infliximab groups, respectively, 605 and 753 µg/d of beclomethasone dipropionate equivalent). This can be considered a moderate dose, and increasing this dose or adding a long-acting  -agonist has been shown to result in a markedly better control of asthma (2) without a significant change in side effects. In addition, the study reports a decrease in exacerbations during a 12-wk period. Exacerbations were considered either moderate (two or more consecutive days with more symptoms or a decrease in morning PEF of more than 20%) or severe (requiring oral corticosteroids). In the placebo group, as many as 72% of the patients experienced an exacerbation, but it is not stated whether these were moderate or severe exacerbations. This is a rather high percentage, which suggests that all may have been moderate exacerbations. As severe exacerbations have a clearly higher impact on the patient, this information should be provided to judge the additional effect of infliximab.
Anti–TNF- is now used for patients with severe and invalidating complaints of Crohn's disease or rheumatoid arthritis. Pulmonologists became familiar with this treatment when severe cases of tuberculosis were found in these patients. The incidence of anti–TNF- induced tuberculosis can be as high as 224/100,000 treated patients. Manifestations are often extrapulmonary, and in 24% of the cases there is disseminated disease (3, 4) with a significant risk of death. Physicians are now more aware of this problem, and when mycobacterial infections are suspected antituberculosis treatment is now advised. But there is still an increased risk as the protective effect of such treatment is estimated not to be higher than 60%.
Therefore, in my opinion, anti–TNF- should be used with much care, and studies on the therapeutic value in asthma should be focused on patients with severe debilitating disease. In such cases, the effects of anti–TNF- should be studied in addition to the best current modalities, which are high doses of inhaled corticosteroids in combination with a long-acting -agonist.
Frans H. Krouwels
OLVG Hospital Amsterdam, Amsterdam, The Netherlands
FOOTNOTES
Conflict of Interest Statement: F.H.K. received $4,950 from various pharmaceutical companies (GlaxoSmithKline; AstraZeneca; Merck, Sharpe & Dohme) for giving lectures at meetings and courses.
REFERENCES
- Erin EM, Leaker BR, Nicholson GC, Tan AJ, Green LM, Neighbour H, Zacharasiewicz AS, Turner J, Barnathan ES, Kon OM, et al. The effects of a monoclonal antibody directed against tumor necrosis factor- in asthma. Am J Respir Crit Care Med 2006;174:753–762.[Abstract/Free Full Text]
- National Institutes of Health; National Heart, Lung, and Blood Institute. Global Initiative for Asthma (GINA): global strategy for asthma management and prevention. Available from: www.ginasthma.com (updated 2005).
- Keane J, Gershon SK, Braun MM. Tuberculosis and treatment with infliximab. N Engl J Med 2002;346:625–626.
- British Thoracic Society Standards of Care Committee. BTS recommendation for assessing risk and for managing mycobacterium tuberculosis infection and disease in patients due to start anti-TNF treatment. Thorax 2005;60:800–805.[Abstract/Free Full Text]
Copyright © 2007 American Thoracic Society
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