Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II)

Inclusion Criteria: * The presence of either limited (cutaneous thickening distal but not proximal to elbows and knees, with or without facial involvement) or diffuse (cutaneous thickening proximal to elbows and knees, often involving the chest or abdomen) scleroderma, as determined by American College of Rheumatology criteria * Dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index) * FVC less than or equal to 80 percent of predicted value at screening and less than or equal to 85 percent predicted at baseline * Onset of the first non-Raynaud manifestation of SSc within the prior 84 months * Presence of any ground glass opacification on thoracic high resolution computerized tomography (HRCT) * Repeat FVC at the baseline visit (Visit 2) within 10 percent of the FVC measured at screening and less than or equal to 85 percent predicted. Exclusion Criteria: * FVC less than 45 percent of predicted value at either screening or baseline * Carbon monoxide diffusing capacity (DLCO) (HBg-corrected) less than 30 percent of predicted value and less than 40 percent of predicted when documentation of pulmonary artery pressures by echocardiogram, right heart catheterization or magnetic resonance imaging identifies clinically significant pulmonary hypertension. All participants with a DLCO less than 40 percent predicted must have documentation of pulmonary artery pressures in order to be considered for inclusion. * FEV1/FVC ratio less than 65 percent at either screening or baseline * Clinically significant abnormalities on HRCT not attributable to scleroderma * Diagnosis of clinically significant resting pulmonary hypertension requiring treatment, as ascertained before study evaluation or as part of a standard of care clinical assessment performed outside of the study protocol * Persistent unexplained hematuria (more than 10 red blood cells per high-power field \[RBCs/hpf\]) * History of persistent leukopenia (white blood cell count less than 4000) or thrombocytopenia (platelet count less than 150,000) * Clinically significant anemia (less than 10g/dl) * Baseline liver function test (LFTs) or bilirubin more than 1.5 times the upper limit of normal, other than that due to Gilbert's disease * Concomitant and present use of captopril * Serum creatinine more than 2.0mg/dL * Uncontrolled congestive heart failure * Pregnancy (documented by urine pregnancy test) and/or breast feeding * Prior use of oral CYC or MMF for more than 8 weeks or the receipt of more than two intravenous doses of CYC in the past * Use of CYC and/or MMF in the 30 days before random assignment * Active infection (lung or elsewhere) whose management would be compromised by CYC or MMF * Other serious concomitant medical illness (e.g., cancer), chronic debilitating illness (other than scleroderma), or unreliability or drug abuse that might compromise the patient's participation in the study * Current use, or use within the 30 days prior to random assignment, of prednisone (or equivalent) in doses of more than 10 mg/day * If of child bearing potential (a female participant \<55 years of age who has not been postmenopausal for \> 5 years and who has not had a hysterectomy and/or oophorectomy), failure to employ two reliable means of contraception (which may include surgical sterilization, barrier methods, spermicidals, intrauterine devices, and/or hormonal contraception). * Use of contraindicated medications; more information on this criterion can be found in the study protocol * Smoking of cigars, pipes, or cigarettes in the 6 months before study entry * Use of medications with putative disease-modifying properties within the past month (e.g., D-penicillamine, azathioprine, methotrexate, Potaba)