Cyclophosphamide versus Placebo in Scleroderma Lung Disease

Interstitial lung disease, which is common in patients with mixed connective tissue disease (MCTD), can progress to severe pulmonary fibrosis. The tyrosine kinase inhibitor imatinib mesylate has recently been shown to prevent experimental pulmonary, dermal, and renal fibrosis. Our patient, a 64‐year‐old woman with MCTD and rapidly progressive pulmonary fibrosis, presented with rapid deterioration despite treatment with immunosuppressants. During 20 weeks of treatment with imatinib mesylate at 400 mg/day, our patient improved significantly according to several outcome measures, including New York Heart Association classification, diffusing capacity for carbon monoxide, 6‐minute walking distance, arterial oxygen pressure, and reduction of ground‐glass opacities seen on high‐resolution computed tomography. No adverse effects of imatinib mesylate were observed. These findings suggest that imatinib mesylate might be effective in patients with fibrotic diseases and warrant the initiation of larger clinical studies on the safety and efficacy of imatinib mesylate in connective tissue diseases.

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of pulmonary fibrosis for twenty weeks with imatinib mesylate in a patient with mixed connective tissue disease

Distler¹,

Manger²,

Spriewald³

et al. 2008

“…In contrast to idiopathic pulmonary fibrosis (IPF), which is an aggressive and rapidly progressive disease, SSc-ILD progresses more slowly (2). A recent placebo-controlled, double-blind study showed a statistically significant but modest (2.53%) beneficial effect of oral cyclophosphamide on lung function, as measured by forced vital capacity (FVC) (3). This small effect was not persistent at 1 year of followup (4), although the patients who had received cyclophosphamide still demonstrated a benefit in the dyspnea score.…”

mentioning

confidence: 99%

Randomized, prospective, placebo‐controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis

Seibold

Denton

Fürst

et al. 2010

119

Objective. Endothelin is implicated as a participatory pathway in systemic sclerosis (SSc). We tested this hypothesis in a 12-month trial of bosentan, a nonselective endothelin receptor antagonist, as a therapy for SSc-related interstitial lung disease (ILD).Method. Patients with SSc and significant ILD were recruited to this prospective, double-blind, randomized, placebo-controlled, parallel group study. The inclusion criteria were designed to select a cohort enriched for patients with active and progressive disease. Exclusion factors included significant pulmonary hypertension. Patients with a diffusing capacity for carbon monoxide of <80% predicted and a 6-minute walk distance of 150-500 meters or a 6-minute walk distance of >500 meters with a decrease in oxygen saturation received bosentan or placebo. The primary efficacy end point was a change in the 6-minute walk distance from baseline up to month 12. Secondary end points included time to death or worsening results of pulmonary function tests (PFTs). The safety and tolerability of bosentan were also assessed.Results. Among the 163 patients, 77 were randomized to receive bosentan, and 86 were randomized to receive placebo. No significant difference between treatment groups was observed for change in the 6-minute walk distance up to month 12. No deaths occurred in this study group. Forced vital capacity and diffusing capacity for carbon monoxide remained stable in the majority of patients in both groups. Significant worsenClinicalTrials.gov identifier: NCT00070590.

“…Patients with abnormal findings on bronchoalveolar lavage (BAL) have evidence of active interstitial lung disease and may experience a decline in lung function and in radiographic progression of ILD as compared with those with normal BAL findings (4)(5)(6)(7)(8). Analysis of BAL fluid can serve as an intermediate measure of disease activity; however, its role in predicting lung function and in guiding treatment decisions in scleroderma patients is unknown.…”

Section: Conclusion Persistently Abnormal Results On Bal Fluid Analymentioning

confidence: 99%

Persistence of abnormal bronchoalveolar lavage findings after cyclophosphamide treatment in scleroderma patients with interstitial lung disease

Mittoo

Wigley

Wise

et al. 2007

Self Cite

Objective. Bronchoalveolar lavage (BAL) is a procedure for sampling the terminal airspace cell population to diagnose alveolitis, a condition that predicts changes in lung function in scleroderma patients. Cyclophosphamide (CYC) stabilizes the progression of lung disease in some, but not all, patients with active alveolitis. However, it is unknown whether the BAL fluid cell count obtained after CYC treatment of alveolitis predicts long-term lung function outcomes and can therefore be used to assist in therapeutic decisionmaking. The purpose of this study was to determine whether CYC therapy for active lung disease alters BAL fluid neutrophil and eosinophil counts and whether the persistence of abnormal BAL findings after CYC therapy predicts a decline in lung function in patients with scleroderma and interstitial lung disease (ILD).Methods. We systematically reviewed the records of scleroderma patients who had active ILD, as evidenced by neutrophilia or eosinophilia on BAL fluid analysis before CYC therapy and on repeat analysis after completion of CYC. Pulmonary function tests (PFTs) were performed before initiation of therapy, at completion of therapy, and during long-term followup (mean ؎ SD 3.6 ؎ 1.94 years).Results. Of the 25 study patients, in only 6 did the BAL fluid cell counts normalize after CYC therapy. No significant differences were observed between the proportions of patients who had a >10% decline in the % predicted DLCO or FVC on the second set of PFTs and had abnormal findings on followup BAL fluid analysis.During long-term followup, patients with persistent alveolitis had a decline in lung function (mean ؎ SD change in % predicted FVC -0.6 ؎ 10.8 liters and mean ؎ SD change in % predicted DLCO -4.7 ؎ 21.43 ml/minute/mm Hg), but their lung function did not significantly differ from that in patients whose BAL fluid cell counts had normalized (P ‫؍‬ 0.70 and P ‫؍‬ 0.62, respectively).Conclusion. Persistently abnormal results on BAL fluid analysis following CYC treatment is a common finding and does not predict a subsequent decline in lung function.