Treatment With Mycophenolate Mofetil and Cyclophosphamide Improves Patient-Reported Outcomes in Scleroderma Lung Disease

Systemic Sclerosis and Scleroderma
Scleroderma is an autoimmune disorder where the body’s immune system attacks its own cells. Scleroderma results in the persistent hardening of the body’s connective tissues, for example the skin. It can affect blood vessels by causing them to harden and thicken, forming vascular lesions. In its most extreme state it can affect the vascular supply to the major organs of the body, eventually causing death.
Researchers determined the effect of treatment with cyclophosphamide and mycophenolate mofetil on patient-reported outcomes in systemic sclerosis-related interstitial lung disease.

Treatment with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) improves overall patient-reported outcomes in patients with systemic sclerosis‐related interstitial lung disease (SSc‐ILD), according to study results published in ACR Open Rheumatology.

In this study, researchers assessed patient-reported outcomes from patients enrolled in the Scleroderma Lung Study 2 ( Identifier: NCT00883129), a randomized controlled trial to compare the treatment of MMF for 2 years to the treatment of oral CYC for 1 year followed by 1 year of placebo.

Investigators randomly assigned 142 patients to receive either oral CYC (n=72) or MMF (n=69). Joint models were developed to investigate patient-reported outcomes over 2 years. The primary end point was the percentage improvement in forced vital capacity (FVC), measured quarterly in the study period. Researchers also evaluated changes in patient-reported outcomes in response to MMF and CYC and the correlation between changes in the FVC% predicted in trial and changes in patient-reported outcomes, and associations with SSc‐ILD disease severity.

Results revealed that patients receiving MMF and CYC experienced substantial improvements in FVC during the study. Patients reported improvements in several outcomes, regardless of whether they had received CYC or MMF. Significant improvements were indicated among both treatment cohorts in terms of scores on the Transitional Dyspnea Index (TDI) and St George’s Respiratory Questionnaire (SGRQ) during the study period. Investigators observed that 29% of patients receiving CYC and 24% receiving MMF met or exceeded the minimally clinical important difference (MCID) estimates for TDI. Furthermore, 28% of patients receiving CYC and 25% receiving MMF met or exceeded the MCID estimates for SGRQ. Moreover, baseline FVC%‐predicted was not correlated with baseline TDI or SGRQ scores; however, improvements in FVC%‐predicted were weakly associated with improvements in TDI and SGRQ scores.

Study limitations included the premature withdrawal of a significant number of patients from active treatment during the study leading to biased estimates, the variations in data point collections, and that the MCID estimates could have been influenced by possible confounders.

Researchers concluded, “The relationship between [patient-reported outcome] measures and the FVC was relatively weak, suggesting that [patient-reported outcomes] provide complementary information about treatment efficacy not captured by changes in the FVC alone in this patient population.”


Volkmann ER, Tashkin DP, LeClair H, Roth MD, Kim G, Goldin J, et al. Treatment with mycophenolate and cyclophosphamide leads to clinically meaningful improvements in patient-reported outcomes in scleroderma lung disease: Results of Scleroderma Lung Study II [published online May 20, 2020]. ACR Open Rheum. doi:10.1002/acr2.11125