Determinants of response to immunosuppressive therapy in idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) response to corticosteroids and cytotoxic medications appears to be the most important determinant of survival. The purpose of this retrospective study was to analyse the determinants of response to immunosuppressive therapy with prednisone alone, or prednisone and cyclophosphamide, in IPF. Twenty five consecutive patients were studied. Initial evaluation in untreated patients included clinical, biological and functional parameters. Sequential evaluation by pulmonary function tests (forced vital capacity (FVC) and transfer factor of the lungs for carbon monoxide (TLCo)) was performed at a 3 month interval. Response to therapy was defined as an improvement in FVC and/or TLCo of more than 10% after 12 months, with maintenance of this improvement for at least another 12 months. Twelve of the 25 patients were classified as responders. A symptomstic disease of less than 12 months duration before onset of therapy related to response. FVC was more impaired in the group of responders when the comparison was limited to patients with an FVC of less than 90%. Bronchoalveolar lavage cell counts were not significantly different between responders and nonresponders. Assessment of pulmonary function after 3 months of treatment was predictive of maintenance of the response or of even further improvement. Patients with improved FVC after 3 months of therapy had a significantly shorter sympto- matic disease before onset of treatment (7.6±7.1 vs 20.2±18.6 months). A beneficial effect of addition of cyclophosphamide was observed only in patients who demonstrated an early but short-lived improvement to steroids. Adverse reactions of immunosuppressive therapy were noticed in 10 patients, and required discontinuation of treatment in six of them. Morbidity from cyclophosphamide toxicity was evident in six patients, whilst five of them failed to demonstrate response to cyclophosphamide. In conclusion, our retrospective study suggests that patients with a shorter symptomatic period prior to initiating treatment are more likely to respond to treatment. Early assessment of changes in FVC in individual patients may provide information regarding the likelihood of response to treatment. Early but short-lived corticosteroid effects may be reverted to sustained therapeutic effects by the addition of cyclophosphamide.