Cyclophosphamide with low or high dose prednisolone for systemic sclerosis lung disease.
OBJECTIVE
To evaluate the safety and efficacy of monthly intravenous pulses of cyclophosphamide (CP) in combination with low or high doses of prednisolone in patients with systemic sclerosis (SSc) related interstitial lung disease (ILD) with FVC < 70% of predicted.


METHODS
An open label, non-parallel arm study, performed in the rheumatology outpatient clinic of a university hospital. Twenty-eight patients with SSc related ILD were evaluated. Endpoint evaluations included the evolution of high resolution computed tomography, pulmonary function tests, skin involvement and dyspnea over 12 months. Patients were treated with monthly IV CP in combination with prednisolone at low (< 10 mg/day; n = 12) or high doses (1 mg/kg/day for 4 weeks, then reducing the prednisolone by 5 mg/day on alternating days each 2 weeks; n = 16).


RESULTS
In the low dose steroid group, no improvement was seen for any endpoint at 6 and 12 months of followup. In the high dose steroid group, at 12 months there was significant improvement in the percentage of "ground glass" parenchymal lung involvement (-5.7%; p = 0.003), as well as in the percentage of predicted FVC (12.4%; p < 0.001), the percentage of predicted DLCO (7.3%; p = 0.029), the percentage of skin involvement (-5.4%; p = 0.01), and the severity of dyspnea (p = 0.012). Substantial improvement was seen as early as 6 months. One patient (low dose group) died from ILD.


CONCLUSIONS
A combination of IV pulse CP with high doses of prednisolone shows promising efficacy in improving the clinical, physiological, and radiological evolution of SSc related ILD with reversal of the underlying alveolitis.
Pakas
Ioannis
I
Department of Pathophysiology, School of Medicine, National University of Athens, Greece.
Ioannidis
John P A
JP
Malagari
Katerina
K
Skopouli
Fotini N
FN
Moutsopoulos
Haralampos M
HM
Vlachoyiannopoulos
Panayiotis G
PG
D000553:Ambulatory Care; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D020551:Pulse Therapy, Drug; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D011239:Prednisolone