A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis

N Engl J Med. 1999 Oct 21;341(17):1264-9. doi: 10.1056/NEJM199910213411703.

Abstract

Background and methods: Patients with idiopathic pulmonary fibrosis have progressive scarring of the lung and usually die within four to five years after symptoms develop. Treatment with oral glucocorticoids is often ineffective. We conducted an open, randomized trial of treatment with a combination of interferon gamma-1b, which has antifibrotic properties, and an oral glucocorticoid. We studied 18 patients with idiopathic pulmonary fibrosis who had not had responses to glucocorticoids or other immunosuppressive agents. Nine patients were treated for 12 months with oral prednisolone alone (7.5 mg daily, which could be increased to 25 to 50 mg daily), and nine with a combination of 200 microg of interferon gamma-1b (given three times per week subcutaneously) and 7.5 mg of prednisolone (given once a day).

Results: All the patients completed the study. Lung function deteriorated in all nine patients in the group given prednisolone alone: total lung capacity decreased from a mean (+/-SD) of 66+/-8 percent of the predicted value at base line to 62+/-6 percent at 12 months. In contrast, in the group receiving interferon gamma-1b plus prednisolone, total lung capacity increased (from 70+/-6 percent of the predicted value at base line to 79+/-12 percent at 12 months, P<0.001 for the difference between the groups). In the group that received interferon gamma-1b plus prednisolone, the partial pressure of arterial oxygen at rest increased from 65+/-9 mm Hg at base line to 76+/-8 mm Hg at 12 months, whereas in the group that received prednisolone alone it decreased from 65+/-6 to 62+/-4 mm Hg (P<0.001 for the difference in the change from baseline values between the two groups); on maximal exertion, the value increased from 55+/-6 to 65+/-8 mm Hg in the group that received combined treatment and decreased from 55+/-6 mm Hg to 52+/-5 mm Hg in the group given prednisolone alone (P<0.001). The side effects of interferon gamma-1b, such as fever, chills, and muscle pain, subsided within the first 9 to 12 weeks.

Conclusions: In a preliminary study, 12 months of treatment with interferon gamma-1b plus prednisolone was associated with substantial improvements in the condition of patients with idiopathic pulmonary fibrosis who had had no response to glucocorticoids.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Connective Tissue Growth Factor
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / administration & dosage*
  • Growth Substances / genetics
  • Humans
  • Immediate-Early Proteins*
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / therapeutic use*
  • Male
  • Middle Aged
  • Prednisolone / administration & dosage*
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / physiopathology
  • Pulmonary Gas Exchange / drug effects
  • Recombinant Proteins
  • Total Lung Capacity / drug effects
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta / genetics

Substances

  • CCN2 protein, human
  • Carrier Proteins
  • Glucocorticoids
  • Growth Substances
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor
  • Interferon-gamma
  • Prednisolone