Therapeutic strategy combining intravenous cyclophosphamide followed by oral azathioprine to treat worsening interstitial lung disease associated with systemic sclerosis: a retrospective multicenter open-label study.
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/m(2) 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 x 10(-5)) at 24 months.


CONCLUSIONS
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.
Bérezné
Alice
A
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), Paris France.
Ranque
Brigitte
B
Valeyre
Dominique
D
Brauner
Michel
M
Allanore
Yannick
Y
Launay
David
D
Le Guern
Véronique
V
Kahn
Jean-Emmanuel
JE
Couderc
Louis-Jean
LJ
Constans
Joël
J
Cohen
Pascal
P
Mahr
Alfred
A
Pagnoux
Christian
C
Hachulla
Eric
E
Kahan
André
A
Cabane
Jean
J
Guillevin
Loïc
L
Mouthon
Luc
L
D000284:Administration, Oral; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001379:Azathioprine / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020551:Pulse Therapy, Drug; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000150:complications; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D003520:Cyclophosphamide; D001379:Azathioprine