Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis.

Abstract

In a randomised, controlled study alternate day prednisolone with an initial high dose phase ("prednisolone only series") has been compared with cyclophosphamide plus alternate day low dose prednisolone ("cyclophosphamide-prednisolone series") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed.Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two ofthe 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamideprednisolone series (three of the seven had stopped treatment because of toxicity).Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive ofoutcome. Analyses ofsubgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment.

Interstitial fibrosis and growth factors.

“…Some of these approaches currently are in clinical trials. For example, cyclophosphamide appears to decrease lymphocytes in the lung (24) and azathioprine suppresses cellular immunity (25). Colchicine and methotrexate appear to reduce inflammation by blocking some cell migration and perhaps by reducing elaboration of extracellular matrix (26).…”

High-Dose Acetylcysteine in Idiopathic Pulmonary Fibrosis

“…[5][6][7][8][9] If this is the case, it may explain why treatment with corticosteroids and immunosuppressive agents results in only slight therapeutic benefit. 3,[10][11][12] An oxidant-antioxidant imbalance may contribute to the disease process in idiopathic pulmonary fibrosis. [13][14][15][16][17][18][19][20] Acetylcysteine, a precursor of the major antioxidant glutathione, given at a daily dose of 1800 mg, has been shown to restore depleted pulmonary glutathione levels [16][17][18][19] and to result in a statistically significant improvement in lung function in patients with fibrosing alveolitis after 12 weeks 18 of treatment.…”

Idiopathic pulmonary fibrosis: treatment options in pursuit of evidence-based approaches

“…While this may be appropriate for treatment with lone corticosteroid therapy [2], colchicine [3,4], cyclophosphamide [5,6] and d-penicillamine [7], care should be taken in generalising the notion to treatment with all currently available drugs. For instance, several years ago, combined low-dose prednisone plus azathioprine, compared with low-dose prednisone alone, did produce significant positive signals in a prospective, double-blind, randomised, placebo-controlled study in patients with newly diagnosed IPF [8].…”