Mycophenolate versus cyclophosphamide for progressive interstitial lung disease associated with systemic sclerosis: a 2-year case control study.
OBJECTIVE
Cyclophosphamide is considered the treatment of choice for interstitial lung disease (ILD) secondary to systemic sclerosis (SSc), albeit having a minimal effect. Although controlled evidence does not exist, mycophenolate is used increasingly in clinical practice as an alternative. We aimed to compare the long-term efficacy of these drugs.


METHODS
Patients from our SSc cohort who received mycophenolate for over 1 year for progressive ILD were 1:1 matched for age, gender, and baseline forced vital capacity (FVC ±3 %) with cyclophosphamide-treated patients. Changes in FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) scans were compared between groups. Changes in pulmonary function tests (PFTs) over at least 1 year in six unmatched control patients, who had denied mycophenolate or cyclophosphamide, also were examined.


RESULTS
FVC, TLC, and DLCO did not change significantly in either mycophenolate (from 79.0 ± 12.5 to 80.2 ± 8.1 to 81.2 ± 11.4, from 71.5 ± 16.1 to 74.3 ± 10.8 to 71.8 ± 13.0, from 56.8 ± 12.0 to 55.2 ± 9.9 to 50.6 ± 8.5, respectively) or cyclophosphamide group (from 77.3 ± 12.5 to 79.7 ± 10.3 to 82.5 ± 12.9, from 64.7 ± 14.9 to 68.6 ± 16.0 to 66.1 ± 15.5, from 53.1 ± 14.3 to 56.4 ± 13.5 to 56.3 ± 6.7, respectively), after 1 or 2 years of treatment. PFTs also remained stable in the control group. In either the mycophenolate or cyclophosphamide groups, six patients remained stable, three improved, and one deteriorated according to the definitions of the American Thoracic Society. However, and despite the fact that patients in the cyclophosphamide group had more extended ILD at baseline, a deterioration of lung HRCT findings at 2 years was noticed after mycophenolate (from 10.0 ± 8.9 to 12.7 ± 8.2, p = 0.039) but not after cyclophosphamide.


CONCLUSIONS
Although these results derive from patients selected for receiving at least 1 year of treatment and therefore they do not represent an intention-to-treat cohort, an eagerness to replace cyclophosphamide by mycophenolate in SSc-associated ILD treatment is not supported.
First Department of Propedeutic and Internal Medicine, Athens University Medical School, Athens, Greece, sty.panopoulos@gmail.com.
Stylianos T
ST
Panopoulos
Vassiliki-Kalliopi
VK
Bournia
Georgia
G
Trakada
Irene
I
Giavri
Charalambos
C
Kostopoulos
Petros P
PP
Sfikakis
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011859:Radiography; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications*; D014109:Total Lung Capacity / Q000502:physiology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000502:physiology
D000893:Anti-Inflammatory Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid