Steroid-sparing effects of pentoxifylline in pulmonary sarcoidosis.
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).


METHODS
Randomized, double-blind, placebo-controlled trial,


METHODS
Clinical Research Center, National Institutes of Health.


METHODS
27 patients with biopsy-confirmed pulmonary sarcoidosis receiving prednisone.


METHODS
Placebo or POF (1200-2000 mg/day) for 10 months, as prednisone was tapered.


METHODS
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.
Park
M K
MK
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1434, USA.
Fontana
Babaali
H
H
Gilbert-McClain
L I
LI
Stylianou
M
M
Joo
J
J
Moss
J
J
Manganiello
V C
VC
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005540:Forced Expiratory Flow Rates / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D055815:Young Adult
D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline