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American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 417, (2007)
© 2007 American Thoracic Society


Correspondence

Infliximab Therapy in Pulmonary Sarcoidosis

To the Editor:

In their article, Baughman and colleagues (1) reported that infliximab therapy in patients with chronic sarcoidosis was associated with a significant improvement in percent predicted FVC after 24 weeks of therapy in a cohort of 138 patients. However, no benefit was demonstrated on the endpoints of the six-minute-walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ), or Borg's CR10 dyspnea score. Post hoc analyses further suggested a greater benefit in patients with more severe disease. The authors conclude that the clinical relevance of the observed FVC improvement remains unclear. Nevertheless, they suggest that their data support further evaluation of anti–TNF-{alpha} therapy in severe chronic sarcoidosis.

In our opinion, the conclusions are too optimistic. This may lead to an uncontrolled use of infliximab in patients with chronic pulmonary sarcoidosis outside new study protocols. First, there is a clear limitation of the study in using FVC percent predicted as primary endpoint. Pulmonary function tests characteristically reveal a restrictive pattern with a reduction in DLCO, although it is not unusual for lung function to be normal (2). Endobronchial sarcoidosis may lead to impairment of airflow and obstructive respiratory physiology. There might be several reasons for a decrease in FVC—for example, bad performance or obesity. Measurement of TLC, RV, and DLCO might be more powerful in reflecting improvement of lung function. In our opinion, measurement of dynamic lung volumes is insufficient to reflect the changes occurring in sarcoidosis with pulmonary involvement. An improvement of 2.8% FVC percent predicted corresponds to an absolute increase of only about 0.080 L. Furthermore, endobronchial disease exists in approximately 70% of patients with stage II or III disease. Thus, changes in FEV1 would also be of interest (not mentioned in the article).

Even the improvement in radiological findings remains questionable. There is no indication of the severity of sarcoidosis in the study population investigated. A radiological classification of patients into stages II to IV might be helpful. Furthermore, a computed tomography scan would be more helpful to observe changes in radiological findings concerning both pulmonary involvement and the status of hilar and mediastinal lymphadenopathy.

The study protocol has shown that the use of infliximab in these patients seems to be safe. On the other hand, O'Shea and colleagues reported the development of pulmonary sarcoidosis occurring in the context of infliximab treatment for ankylosing spondylitis (3).

Since the study design shows several limitations, the investigators cannot suggest a potential beneficial effect of this expensive drug or propose further evaluation.

Christian M. Kähler, Peter Heininger, Judith Loeffler-Ragg and Helene Vogelsinger

Innsbruck Medical University, Innsbruck, Austria

FOOTNOTES

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

  1. Baughman RP, Drent M, Kavuru M, Judson MA, Costabel U, du Bois R, Albera C, Brutsche M, Davis G, Donohue JF, et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med 2006;174:795–802.[Abstract/Free Full Text]
  2. Dunn TL, Watters LC, Hendrix C, Cherniack RM, Schwarz MI, King TE. Gas exchange at a given degree of volume restriction is different in sarcoidosis and idiopathic pulmonary fibrosis. Am J Med 1988;85:221–224.[Medline]
  3. O'Shea FD, Marras TK, Inman RD. Pulmonary sarcoidosis developing during infliximab therapy. Arthritis Rheum 2006;55:978–981.[CrossRef][Medline]




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2007 American Thoracic Society