© 2007 American Thoracic Society
Infliximab Therapy in Pulmonary SarcoidosisFrom the Authors:The letter from Dr. Kähler and his colleagues raises several issues about our recently completed trial of infliximab for chronic pulmonary sarcoidosis (1). The authors comment that changes in other lung volumes, such as TLC or RV, may have been more sensitive to response to therapy. However, these volumes have not been systematically studied in sarcoidosis during therapy. Changes in DLCO have been shown with therapy for sarcoidosis. However, comparing 18 months of corticosteroid therapy versus no treatment, the changes for DLCO were less than 10% of the baseline values (2). Since we were concerned about the inherent variability of the DLCO, we chose to use the FVC as our primary endpoint of the study. Although our changes were modest, studies comparing 18 months of corticosteroids versus placebo have shown a less than 10% improvement in FVC compared with placebo (2, 3). The patients in the current study were all receiving stable, chronic therapy. The study was designed to determine whether additional therapy would be associated with an increase in lung function. As noted in the article, patients with more advanced disease had a greater than 5% improvement in FVC compared with placebo. The changes in chest roentgenogram were supportive of the changes we found in the FVC. This was a planned analysis, using the objective scoring technique developed by Muers and coworkers (4), read by two radiologists in a blinded fashion. We also analyzed the Scadding stages of the chest roentgenogram. We reported at the European Respiratory Society our detailed analysis of the chest roentgenograms in this study (5). We found the Scadding scoring system less reproducible than the scoring technique of Muers and coworkers. Our current study was performed to support several previous case series reporting effectiveness of infliximab for refractory cases of sarcoidosis (6). This study is the first double-blind, randomized controlled trial of chronic pulmonary sarcoidosis. We did not feel it was ethical to withdraw corticosteroid therapy from the placebo-treated patients. If we had done so, we may have been able to demonstrate a larger response to infliximab. Kähler and coworkers also cite the report by O'Shea and coworkers of a patient with ankylosing spondylitis treated with infliximab for 5 years who developed pleuritic chest pain, a pleural effusion, and adenopathy (7). The patient was eventually diagnosed as having sarcoidosis. Whenever one is giving infliximab or other immunomodulatory agents, one must always be vigilant for disease worsening or superimposed infection.
University of Cincinnati Medical Center, Cincinnati, Ohio FOOTNOTES Conflict of Interest Statement: R. P. B. has been a consultant and received support for various clinical trials from Centocor, the manufacturers of infliximab. REFERENCES
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