Abstract
Objective
To evaluate the effects and safety of 6-month intravenous cyclophosphamide (CYC) followed by 18-month oral azathioprine (AZA) therapy in patients with systemic sclerosis (SSc) and worsening interstitial lung disease (ILD).
Methods
All patients presented with ILD and worsened forced vital capacity (FVC) and/or total lung capacity of more than 10% and/or DLCO of more than 15% during the previous year. Treatment was 6 monthly pulses of 0.6 g/m2 CYC followed by oral AZA for 18 months on disease stabilization or improvement. The endpoint was the rate of percentage change in pulmonary function tests (PFT) after 6 and 24 months.
Results
Twenty-seven patients with SSc (20 females) were recruited. Age and disease duration before CYC therapy were (mean ± SD) 49.4 ± 15 years and 75.5 ± 87.8 months, respectively. Mean baseline FVC was 67% ± 19% of predicted value. At 6 months, in 7 (26%) patients disease was improved, in 12 (44%) stabilized, and in 8 (30%) worsened. Among the 19 (70%) responders, 15 received AZA and 4 declined. Twenty-three completed 2-year followup, 3 died, and one dropped out. Six (22.2%) had improved, 8 (29.6.%) were stable, and 13 (48.2%) had worsened. Evolution of the slope of FVC (in % per year) varied from –15.5 prior to treatment to +3 (p = 0.004) at 6 months and to +1 (p < 5 ×10−5) at 24 months.
Conclusion
Intravenous CYC followed by oral maintenance immunosuppressive therapy for worsening ILD was well tolerated and was associated with stable or improved PFT in 70% and 51.8% of SSc patients at 6 months and 2 years, respectively.
Key Indexing Terms:Footnotes
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A. Bérezné, MD; B. Ranque*, MD; V. Le Guern, MD; P. Cohen, MD; A. Mahr, MD; C. Pagnoux, MD; L. Guillevin, MD; L. Mouthon, MD, PhD, Paris Descartes University, Faculty of Medicine; Department of Internal Medicine and Reference Center for Necrotizing Vasculitides and Systemic Sclerosis, Cochin Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP); D. Valeyre*, MD, Paris Nord University, Faculty of Medicine; Department of Pneumology, Avicenne Hospital, AP-HP; M. Brauner, MD, Paris Nord University, Faculty of Medicine; Department of Radiology, Avicenne Hospital, AP-HP; Y. Allanore, MD, PhD; A. Kahan, MD, Paris Descartes University, Faculty of Medicine, Department of Rheumatology A, Cochin Hospital and AP-HP; D. Launay, MD; E. Hachulla, MD, PhD, Lille 2 University, Faculty of Medicine, Department of Internal Medicine and National Reference Center of Vascular Manifestations of Scleroderma, Regional University Hospital Claude-Huriez Hospital; J-E. Kahn, MD, Department of Internal Medicine, Foch Hospital; L-J. Couderc, MD, Department of Pneumology, Foch Hospital; J. Constans, MD, Department of Vascular Medicine, CHU-Hôpitaux de Bordeaux, Saint André Hospital; J. Cabane, MD, Department of Internal Medicine, Saint-Antoine Hospital.
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↵ Both authors contributed equally to the work.
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Supported by the Association des sclérodermiques de France under the auspices of the Groupe Français de Recherche sur la Sclérodermie (GFRS) and the Société Nationale Française de Médecine Interne.
- Accepted for publication January 17, 2008.
