PURPOSE: Anecdotal evidence has suggested improvement in extrapulmonary sarcoidosis with infliximab therapy, but this has not been prospectively studied. The purpose of this study was to evaluate the efficacy of infliximab on extrapulmonary sarcoidosis in patients with chronic pulmonary sarcoidosis who are symptomatic despite treatment.
METHODS: One hundred thirty-eight patients were randomized (1:1:1) to placebo, 3 or 5mg/kg infliximab at 34 centers. Patients were infused at week 0, 2, 6, 12, 18, 24 and then followed through week 52. Patients were included with a diagnosis of sarcoidosis for [greater than or equal to] 1 year and therapy for [greater than or equal to] 3 months with prednisone ([greater than or equal to] 10 mg/day) and/or immunomodulators. Physicians assessed each of 17 extrapulmonary organs and the lungs for involvement at each visit on a 0-6 scale (0=not affected; 6=very severe). The total of extrapulmonary scores were compared across the groups. Serum angiotensin converting enzyme (ACE) levels were measured as an indication of total granuloma burden.
RESULTS: The mean ([+ or -] SD) extrapulmonary total scores and ACE levels were similar at baseline across the groups. Mean scores fell steadily throughout the 24 week period in both treated groups. At week 24, there was a significant reduction in combined infliximab group (p=0.002). Mean ACE levels rose in the placebo group at 12 and 24 weeks whereas they fell significantly in both treatment groups at both times.
CONCLUSION: Infliximab appears to be effective in reducing extrapulmonary sarcoidosis involvement as assessed by physicians using a novel 7 point assessment tool. ACE levels are also reduced by infliximab, prior to the detection of any clinical improvement in the extrapulmonary total score.
CLINICAL IMPLICATIONS: Addition of infliximab to corticosteroid therapy with or without immunomodulators is a promising new treatment strategy for patients with extrapulmonary involvement. Further validation of the clinical meaningfulness of changes in the total score needs to occur. Additional follow up off treatment will be important to assess the duration of the improvements noted.
DISCLOSURE: M Judson, Grant monies (from industry related sources) Research grants; Employee; Consultant fee, speaker bureau, advisory committee, etc.
M. A. Judson MD * U. Costabel MD M. Drent MD M. Kavuru MD R. M. duBois MD K. H. Lo PhD R. Schlenker-Herceg MD E. S. Barnathan MD R. P. Baughman MD Medical University of South Carolina, Charleston, SC
COPYRIGHT 2005 American College of Chest Physicians
COPYRIGHT 2005 Gale Group