Interstitial Lung Disease in Systemic Sclerosis : should mild disease be treated

Interstitial Lung Disease in Systemic Sclerosis: Should Mild Disease Be Treated?

by Dr. Sabrina Hoa

Dr. Sasha Bernatsky, Gaetan Baril, President of Scleroderma Quebec, Dr. Sabrina Hoa and Dr. Marie Hudson

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by various degrees of skin fibrosis and internal organ involvement. Interstitial lung disease (ILD), or pulmonary fibrosis, is a common complication of SSc, affecting up to 50% of patients. Immunosuppressive drugs are currently used to treat SSc-ILD, particularly in patients with pulmonary symptoms (e.g. shortness of breath or cough), severe lung function impairment, or progressive worsening disease. However, the usefulness of these drugs in patients with normal or mildly impaired lung function is currently unclear, given that this patient population was mostly excluded from randomized controlled trials. Yet, SSc-ILD with normal or mildly impaired lung function is frequent, representing approximately half of all SSc-ILD patients.

In the course of her Masters of Epidemiology thesis project at McGill University, Dr. Hoa was interested in exploring the role of immunosuppressive drugs, namely cyclophosphamide and mycophenolate mofetil, in the treatment of patients with mild SSc-ILD. Using data collected in the Canadian Scleroderma Research Group (CSRG) registry from 2004 to 2017, she studied the characteristics and outcomes of 116 patients with mild SSc-ILD. About 10% of these patients were exposed to cyclophosphamide or mycophenolate mofetil mostly for joint and skin disease. After one year, the forced vital capacity (a measure of lung function) of patients who were exposed to these drugs was compared with that of patients who were not exposed to these drugs.

What were the results? Patients with mild SSc-ILD who were exposed to immunosuppressive drugs for reasons other than lung disease had better lung function test results at one year compared to patients who were not exposed, even after adjusting for baseline lung function values, disease duration, extent of skin disease and shortness of breath scores. Moreover, none of the patients who were exposed to immunosuppressive drugs progressed over the next two years, whereas up to 25% of patients who were not exposed to these drugs progressed over this timeframe.

These preliminary results are very interesting in that they suggest that immunosuppressive drugs may have a disease-modifying role in the treatment of early SSc-ILD. Future randomized controlled studies looking at efficacy of therapies in SSc-ILD should include patients with mild SSc-ILD, as these patients may also benefit from disease-altering therapies. Further research also needs to be done to better characterize the predictors of disease progression among patients with mild SSc-ILD.

Dr. Hoa has now completed her Masters of Epidemiology and is very grateful to her supervisors, Dr. Marie Hudson and Dr. Sasha Bernatsky, for their exceptional mentorship. She is also thankful to Dr. Murray Baron, director of the CSRG, and all the patients and researchers who have contributed to the richness of the CSRG registry. She is deeply grateful to Sclérodermie Québec, the Scleroderma Research Chair of the University of Montreal, The Arthritis Society, the Canadian Institutes for Health Research and the Centre Hospitalier de l’Université de Montréal (CHUM) Foundation for their financial support during her postdoctoral fellowship training. Dr. Hoa has now been appointed Assistant Professor in the Department of Medicine, Faculty of Medicine, at University of Montreal and in the Division of Rheumatology at the CHUM. As a clinician-researcher, she hopes to further knowledge on the optimal use of therapies to improve outcomes of all people affected by scleroderma.