Use Immunosuppressants Cautiously in Scleroderma-linked Lung Disease, Study Advises

Using immunosuppressive therapy to treat interstitial lung disease (ILD) associated with scleroderma (SSc) should be done carefully and with close monitoring, a study reports.

The research, published in the journal Arthritis Research & Therapy, is titled “Systemic sclerosis associated interstitial lung disease – individualized immunosuppressive therapy and course of lung function: results of the EUSTAR group.“

Immunosuppressive therapy is often used in SSc. But information is scarce on the relationship between immunosuppressant prescriptions and the course of lung function in patients with SSc-ILD.

A research team analyzed data on 3,778 SSc-ILD patients enrolled in the European Scleroderma Trials and Research Group (EUSTAR) database from 2004 to 2014. The patients were over 18 years old, and were diagnosed with ILD by computer tomography or chest x-rays.

Patients who had received immunosuppressive therapy at least once were compared with  patients who had never received it.

Researchers observed that patients who used immunosuppressive therapy had a more severe and active ILD compared than those who had not been prescribed such therapy.

The majority of patients with SSc-ILD — 71 percent (2,681 patients) — received immunosuppressive therapy, compared with 40 percent among SSc patients without ILD.

The immunosuppressive therapy varied widely, with some stand-alone treatments and some combination regimens. The most frequent treatment was monotherapy with glucocorticoids (prednisone), taken by 30.6 percent of the patients analyzed.

Less frequently, patients were on combination therapies of glucocorticoids plus cyclophosphamide (11.9 percent), azathioprine (9.2 percent), methotrexate (8.7 percent), or mycophenolate mofetil (7.3 percent).

Intensive immunosuppressive therapy (either mycophenolate mofetil and glucocorticoids, or cyclophosphamide or cyclophosphamide plus glucocorticoids) was used in patients with more severe ILD and the poorest pulmonary function.

Patients receiving methotrexate monotherapy had the best lung function, as assessed by forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), and total lung capacity (TLC). They also had the lowest prevalence of pulmonary hypertension, and shorter disease duration.

In contrast, patients on cyclophosphamide monotherapy had the highest severity of disease, the worst lung function levels, severe skin fibrosis, and the worse values on the modified Rodnan skin score.

Researchers grouped patients according to mild, moderate and severe impairment of lung function at the start of therapy. The results showed that all three groups had significantly worse lung function when patients were on mmunosuppressive therapy than when they were not treated with immunosuppressive drugs.

The team concluded that specific types of immunosuppressive therapy display a slight influence on the progression of lung function, namely glucocorticoids or methotrexate.

“None of the specific types of IS [immunosuppressive therapy] was clearly superior to another in influencing the course of lung function in any DLCO or FVC group,” the researchers wrote. “Thus, if carefully monitored for changes in lung function, patients with SSc-ILD with only small PFT [pulmonary function test] impairment might benefit from on-demand IS instead of ongoing IS.”

According to the team, the “data favor distinguished decision-making, pointing to either watchful waiting and close monitoring in the early stages or start of immunosuppressive treatment in moderately impaired lung function.”

Based on the results, the research team said it does not support the liberal use of glucocorticoids in patients with SSc-ILD.