ab22504

Intravenous cyclophosphamide therapy for systemic sclerosis. A single-center experience and review of the literature with pooled analysis of lung function test results

P. Airò, E. Danieli, G. Parrinello¹, C.M. Antonioli, I. Cavazzana, P. Toniati, F. Franceschini, R. Cattaneo

Rheumatoloy, Allergology and Clinical Immunology and ¹Medical Statistics, Spedali Civili and University of Brescia, Italy

ABSTRACT
Objective
Oral cyclophosphamide (CYC) is a promising therapy for Systemic Sclerosis (SSc)- related interstitial lung disease (ILD). The use of intravenous (iv) pulses has been considered as an alternative route of drug administration, possibly associated with reduced toxicity. Our objectives were to re-evaluate our experience with iv CYC, to review the literature, and to pool our results with those available from other groups, improving the statistical power of the analysis.

Methods
1) Retrospective analysis of our center experience on 16 patients with SSc and active alveolitis, treated with iv CYC 750 mg + 6-methylprednisolone 125 mg every 3 weeks. 2) Pooled analysis of papers published in peer-reviewed journals reporting detailed data on each patient treated with iv CYC. The end-point was modification in the results of lung function tests (LFT) after 6 months. Piecewise regression analysis was performed using a linear mixed-effects model adjusted for baseline values to evaluate the changes in LFT.

Results
Retrospective analysis. In the period before therapy there was a significant deterioration in FVC (in 6 months: -4.3%; p=0.0009) and DLCO (-2.1%; p=0.018). After 6 months of treatment there was a modest improvement in the FVC (+2.7% p=0.08) and DLCO (+2.2%; p=0.08).
Pooled analysis. In 53 evaluable patients, the improvement in LFT reached conventional statistical signifcance (FVC: +2.85%; 95% confidence intervals: +0.04, +5.66%; p= 0.04. DLCO: +4.4%; 95% confidence intervals: +1.2%, +7.5%; p<0.001).

Conclusion
Iv CYC for 6 months can achieve a small, but significant improvement of LFT in patients with SSc and active alveolitis.

Key words
Systemic sclerosis, cyclophosphamide, interstitial lung disease.

Please address correspondence and reprint requests to: Dr Paolo Airò, Servizio di Reumatologia, Allergologia ed Immunologia Clinica, Spedali Civili, Piazzale Spedali Civili, 25124 Brescia, Italy.
E-mail: airo@bresciareumatologia.it