Steroid-sparing effects of pentoxifylline in pulmonary sarcoidosis.

Abstract

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.

• Authors: M K Park, Fontana Jr, H Babaali, L I Gilbert-McClain, M Stylianou, J Joo, J Moss, V C Manganiello
• Journal: Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG (Sarcoidosis Vasc Diffuse Lung Dis) Vol. 26 Issue 2 Pg. 121-31 (Jul 2009) ISSN: 1124-0490 [Print] Italy
• PMID: 20560292 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Intramural)

Chemical References

• Phosphodiesterase Inhibitors
• Pentoxifylline

Topics

• Adolescent
• Adult
• Aged
• Biopsy
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Forced Expiratory Flow Rates (drug effects)
• Humans
• Hypertension, Pulmonary (drug therapy, pathology, physiopathology)
• Male
• Middle Aged
• Pentoxifylline (administration & dosage, therapeutic use)
• Phosphodiesterase Inhibitors (administration & dosage, therapeutic use)
• Respiratory Function Tests
• Treatment Outcome
• Young Adult