Use of leflunomide in patients with chronic hypersensitivity pneumonitis

BMC Pulm Med. 2020 Jul 21;20(1):199. doi: 10.1186/s12890-020-01227-2.

Abstract

Background: Prednisone has been shown to reverse lung function declines in hypersensitivity pneumonitis patients without established fibrosis. Second line immunosuppressants like azathioprine and mycophenolate mofetil have a steroid sparing effect and improve DLCO. There is no published literature on the use of leflunomide in such patients.

Methods: We reviewed our experience with leflunomide for treatment of chronic hypersensitivity pneumonitis in 40 patients. We stratified patients according to the presence or absence of significant (> 20%) fibrosis. We studied the effect of leflunomide on FVC and DLCO trajectory and reported the changes at 12 months.

Results: Treatment with leflunomide tended to improve the estimated FVC slope from 0.18 ± 1.90% (SEM) of predicted per year to 4.62 ± 1.65% of predicted (NS, p = 0.118). It significantly improved the FVC at 12 months of treatment by 4.4% of predicted (p = 0.02). DLCO continued to increase at 1.45 ± 1.44% (SEM) of predicted per year. Non-fibrotic cHP patients had the largest gain in pulmonary function. Their FVC increased by 8.3% (p = 0.001) and DLCO by 4.8% (p = 0.011). Patients with fibrotic cHP did not improve. Leflunomide treatment was associated with significant gastrointestinal and other adverse effects leading 40% of patients to discontinue therapy. It had a significant steroid sparing effect with half the patients weaned off prednisone entirely.

Conclusions: Leflunomide appears to be a fairly well tolerated steroid sparing immunosuppressant that improves pulmonary function in cHP patients. It is most effective in patients without significant fibrosis.

Keywords: Fibrosis; Hypersensitivity pneumonitis; Immunosuppressant; Leflunomide; Pulmonary function.

MeSH terms

  • Adult
  • Aged
  • Alveolitis, Extrinsic Allergic / drug therapy*
  • Alveolitis, Extrinsic Allergic / physiopathology
  • Carbon Monoxide
  • Chronic Disease
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Leflunomide / therapeutic use*
  • Linear Models
  • Male
  • Middle Aged
  • Retrospective Studies
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vital Capacity

Substances

  • Immunosuppressive Agents
  • Carbon Monoxide
  • Leflunomide