Correspondence

Tumor Necrosis Factor α in Refractory Asthma

N Engl J Med 2006; 354:2074-2075May 11, 2006

Article

To the Editor:

In our opinion, the randomized clinical trial by Berry et al. (Feb. 16 issue)1 appears to mitigate the excitement that has been generated in recent years concerning the use of tumor necrosis factor α (TNF-α) inhibitors in the management of refractory asthma.2 In an open-label study,3 12 weeks of treatment with etanercept resulted in a substantial improvement in symptoms; all but one of the patients were able to discontinue the use of bronchodilators. By contrast, the observed statistically significant improvement in quality-of-life and symptom scores in the trial by Berry et al. is probably not of clinical relevance, and none of the patients could discontinue or reduce the use of nebulized or oral treatment.

Examination of the individual quality-of-life scores and comparison of the data obtained in the placebo and etanercept treatment periods suggest that only two patients would unambiguously benefit from this expensive treatment. It is unfortunate that it was not possible to dissect out from the data presented any specific characteristics that would clearly identify those who would have a response to etanercept. In our opinion, the data provided in this small study do not support the use of etanercept for these patients.

Chiara Oliveri, M.D.
Riccardo Polosa, M.D.
Università di Catania, 95125 Catania, Italy

3 References

1. 1

   Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor α in refractory asthma. N Engl J Med 2006;354:697-708
   Full Text | Web of Science | Medline

2. 2

   Russo C, Polosa R. TNF-α as a promising therapeutic target in chronic asthma: a lesson from rheumatoid arthritis. Clin Sci (Lond) 2005;109:135-142
   CrossRef | Web of Science | Medline

3. 3

   Howarth PH, Babu KS, Arshad HS, et al. Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax 2005;60:1012-1018
   CrossRef | Web of Science | Medline

Author/Editor Response

Our pilot study was intended to investigate TNF-α as a potential therapeutic target in patients with refractory asthma; it was not designed to evaluate etanercept as a treatment. Therefore, we are more circumspect than Oliveri and Polosa in our interpretation of the clinical significance of our findings and the number of persons who responded to therapy. However, we agree that the response to etanercept is likely to be variable in a larger population, since the clinical and pathological features of refractory asthma are known to be heterogeneous1,2 and the response to other effective treatments such as methotrexate shows substantial variability.3

The challenge for clinicians is to carry out clinical trials that are sufficiently powered and appropriately designed to identify clinical and pathological features associated with the success of expensive and potentially toxic treatments such as etanercept. One promising candidate is the expression of membrane-bound TNF-α on peripheral-blood monocytes, since this was closely related to the response to treatment with etanercept in our study.

Mike A. Berry, M.R.C.P.
Ian D. Pavord, D.M., F.R.C.P.
University Hospital of Leicester National Health Service Trust, Leicester LE3 9QP, United Kingdom
ian.pavord@uhl-tr.nhs.uk

3 References

1. 1

   Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med 2000;162:2341-2351
   Medline

2. 2

   Pavord ID, Birring SS, Berry MA, Green RH, Brightling CE, Wardlaw AJ. Multiple inflammatory hits and the pathogenesis of airways disease. Eur Respir J (in press).
   

3. 3

   Corrigan CJ, Shiner RJ, Shakur BH, Ind PW. Methotrexate therapy of oral corticosteroid-dependent asthmatics reduces serum immunoglobulins: correlation with clinical response to therapy. Clin Exp Allergy 2005;35:579-584
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Richard M Effros, Hari Nagaraj. (2007) Asthma: new developments concerning immune mechanisms, diagnosis and treatment. Current Opinion in Pulmonary Medicine 13:1, 37-43
   CrossRef