Early Immunosuppressive Treatment May Prevent ILD Progression in SSc Patients, Study Suggests

Immunosuppressive treatment of early-stage interstitial lung disease (ILD) in people with systemic sclerosis may be a potential therapeutic option to prevent ILD progression, a study suggests. 

The study, “Association between immunosuppressive therapy and course of mild interstitial lung disease in systemic sclerosis,” was published in the journal Rheumatology.

ILD is a general term used to describe a large group of disorders that cause scarring (fibrosis) of the lungs. ILD is associated with several lung conditions including idiopathic pulmonary fibrosis and systemic sclerosis (systemic scleroderma or SSc).

SSc is an autoimmune disease of the connective tissue characterized by fibrosis of internal organs. ILD is a common complication of SSc, affecting up to 50% of patients.

People with moderately severe, active SSc are typically treated with immunosuppressants, such as cyclophosphamide (CYC; sold under the brand name Cytoxan by Baxter Healthcare, among others), and mycophenolate mofetil (MMF; sold by Genentech under the brand name CellCept).

These medications, whose use is supported by clinical trials, can halt the progression of moderately severe SSc. However, in patients with established lung fibrosis, these therapies are ineffective in improving lung function.

In the early course of the disease — when lung function is still normal or only slightly impaired — intervention with these immunosuppressants may be an opportunity to prevent lung disease progression. But, as SSc patients with mild ILD were excluded from clinical trials testing the effectiveness of immunosuppressive therapies, little is known about their benefits in this patient population. 

To help fill this gap, researchers at McGill University and the Jewish General Hospital in Montreal, Canada — part of the nationwide Canadian Scleroderma Research Group (CSRG) — analyzed the medical records of SSc patients with mild ILD in the CSRG registry to determine if the use of these therapies helped improve lung function.

The forced vital capacity (FVC, % predicted) test — a measure of respiratory capacity — was used as an indicator of lung function. The researchers compared the FVC values of patients who had been treated for one year with CYC or MMF to those of patients who did not receive immunosuppressive treatment. They also assessed if the treatment made a difference between patients with mild SSc-IDL versus those with more severe lung impairment. 

After analyzing the database, the team identified 116 (47%) patients with mild SSc-IDL (FVC higher than 85%), 130 (52%) with moderate SSc-ILD (FVC between 45%–85%), and three (1.2%) with severe SSc-IDL (FVC below 45%). All patients had SSc for less than seven years, and none had been treated with CYC or MMF before the study period.

Results showed that SSc patients with mild ILD who were treated with CYC or MMF had a higher FVC after one year — an average of 8.49% more — compared with those who did not have the treatment. In contrast, SSc patients with moderate ILD did not show significant FVC improvements with CYC or MMF treatment, compared with those in the untreated group.

Overall, treated patients with mild ILD experienced greater improvement in FVC values compared with patients with moderate ILD.

The researchers then conducted an additional analysis by examining FVC after two years, as well as the diffusion capacity of the lungs for carbon monoxide (DLCO) — a measure of gas exchange efficiency — at one and two years, and disease progression at one and two years.

Patients with mild SSc-ILD treated with CYC or MMF experienced no disease progression over two years, whereas the disease progressed in 18.5% of the untreated patients after one year, and in 24.6% of untreated patients after two years.

No changes in DLCO were observed after one or two years, with or without treatment. Despite these results, the researchers found that untreated patients with mild-ILD, who had lower DLCO values at the beginning of the study, had a higher risk of disease progression after two years.

A survival analysis showed that survival times between treated and untreated groups with mild SSc-ILD were no different. However, survival time in patients with moderate ILD was lower, regardless of CYC/MMF treatment.

Taken together, the data showed that “CYC/MMF exposure at baseline was associated with higher FVC values, and a lower risk of progression among subjects with mild ILD,” the researchers wrote, suggesting that “a window of opportunity exists for the treatment of SSc-ILD.”

“Further research is urgently needed to define the predictors of disease progression among mild SSc-ILD patients, especially as there is growing interest in the therapeutic opportunities for the very early stages of SSc disease,” the team added.