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Steroid-sparing effects of pentoxifylline in pulmonary sarcoidosis
1Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1434, USA.
Background:
Agents that target pro-inflammatory cytokines may be useful in pulmonary sarcoidosis.
Objective:
To determine effectiveness of a non-selective cyclic nucleotide phosphodiesterase (PDE) inhibitor, pentoxifylline (POF).
Design:
Randomized, double-blind, placebo-controlled trial,
Setting:
Clinical Research Center, National Institutes of Health.
Patients:
27 patients with biopsy-confirmed pulmonary sarcoidosis receiving prednisone.
Intervention:
Placebo or POF (1200-2000 mg/day) for 10 months, as prednisone was tapered.
Measurements:
Primary endpoints: sustained improvement in two or more pulmonary function parameters, or a combination of one pulmonary function parameter and dyspnea.
Results:
Except for one patient, primary endpoints were not reached in POF-treated patients. Therefore, a post hoc analysis was performed. The observed relative risk reduction for flares associated with POF treatment was 54.9% (95% CI 0.21, 0.89) and the absolute risk reduction was 50.6% (95% CI 0.22, 0.80). Compared to placebo treatment, in the POF group, the mean prednisone dose was lower at 8 and 10 months (p = 0.007 and 0.01 respectively), and there was a trend towards less prednisone usage over the entire study period (p = 0.053), as determined by cumulative change analysis.
Conclusions:
Although our exploratory post hoc analysis suggested that POF reduced flares and had steroid-sparing effects, given the study limitations, definitive conclusions cannot be drawn regarding the efficacy of POF in pulmonary sarcoidosis. In addition, gastrointestinal side-effects, at the doses used, would seem to limit the use of POF in treating pulmonary sarcoidosis. Overall, however, this trial may provide a basis for using more specific, better-tolerated, PDE inhibitors in future clinical trials.
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