Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial

Ann Intern Med. 2012 Sep 18;157(6):398-406. doi: 10.7326/0003-4819-157-6-201209180-00003.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder of unknown cause with no effective treatment. Cough affects up to 80% of patients with IPF, is frequently disabling, and lacks effective therapy.

Objective: To determine the efficacy of thalidomide in suppressing cough in patients with IPF.

Design: 24-week, double-blind, 2-treatment, 2-period crossover trial. (ClinicalTrials.gov registration number: NCT00600028)

Setting: 1 university center.

Participants: 98 participants were screened, 24 were randomly assigned, 23 received treatment (78.3% men; mean age, 67.6 years; mean FVC, 70.4% predicted), and 20 completed both treatment periods.

Measurements: The primary end point was cough-specific quality of life measured by the Cough Quality of Life Questionnaire (CQLQ). Secondary end points were visual analogue scale of cough and the St. George's Respiratory Questionnaire (SGRQ). For all measures, lower scores equaled improved cough or respiratory quality of life.

Results: CQLQ scores significantly improved with thalidomide (mean difference vs. placebo, -11.4 [95% CI, -15.7 to -7.0]; P < 0.001). Thalidomide also significantly improved scores on the visual analogue scale of cough (mean difference vs. placebo, -31.2 [CI, -45.2 to -17.2]; P < 0.001). In participants receiving thalidomide, scores from the total SGRQ, SGRQ symptom domain, and SGRQ impact domain improved compared with those of participants receiving placebo. Adverse events were reported in 74% of patients receiving thalidomide and 22% receiving placebo; constipation, dizziness, and malaise were more frequent with thalidomide.

Limitation: This was a single-center study of short duration and small sample size focused on symptom-specific quality of life.

Conclusion: Thalidomide improved cough and respiratory quality of life in patients with IPF. A larger trial is warranted to assess these promising results.

Primary funding source: Celgene Corporation.

Publication types

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

MeSH terms

  • Aged
  • Antitussive Agents / adverse effects
  • Antitussive Agents / therapeutic use*
  • Constipation / chemically induced
  • Cough / drug therapy*
  • Cough / etiology
  • Dizziness / chemically induced
  • Double-Blind Method
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / complications*
  • Linear Models
  • Male
  • Middle Aged
  • Quality of Life
  • Surveys and Questionnaires
  • Thalidomide / adverse effects
  • Thalidomide / therapeutic use*
  • Treatment Outcome

Substances

  • Antitussive Agents
  • Thalidomide

Associated data

  • ClinicalTrials.gov/NCT00600028