Interstitial Lung Disease in Scleroderma Patients Treatable with Chemotherapy and Immunosuppression, Study Reports

Scleroderma patients with worsening interstitial lung disease would likely benefit from a treatment regimen consisting of cyclophosphamide pulses, followed by maintenance with the immunosuppressant mycophenolate mofetil (CellCept), researchers reported. The study highlighted the desperate need for better treatments, as slowing progression is the only option now available.

Earlier studies have suggested that treatment with the chemotherapeutic drug cyclophosphamide might benefit this particular patient group. Three trials showed small improvements in forced vital capacity (FVC), but the effect was transient, and could no longer be detected one year after treatment discontinuation. Results suggested that a maintenance treatment is necessary to maintain the results.

The study, “Mycophenolate mofetil following cyclophosphamide in worsening systemic sclerosis-associated interstitial lung disease,“ investigated if cyclophosphamide in combination with  mycophenolate mofetil could be effective as a maintenance therapy.

Researchers at Lille University and Lille University Hospital, France, retrospectively analyzed 20 systemic sclerosis patients with worsening interstitial lung disease who received the therapeutic combination. Patients were treated with six to 12 pulses of cyclophosphamide. Mycophenolate mofetil drug treatment started one month after the last cyclophosphamide dose.

All were treated with mycophenolate mofetil for six months, and 16 of them continued for 12 months. Findings, published in the Journal of Scleroderma and Related Disorders, showed that at the end of the cyclophosphamide treatment, lung disease had improved in 35 percent of the patients and stabilized in 50 percent, as measured by pulmonary function tests.

After six months of mycophenolate mofetil treatment, 50 percent of patients had improved, and another 20 percent had stabilized. During the following six months, the treatment was stopped in four patients who continued to deteriorate. At 12 months, figures were 45 percent improved, 10 percent stabilized, and 45 percent worsened.

Further analysis revealed that a longer treatment period with cyclophosphamide, before the start of mycophenolate mofetil, was tied to better outcomes, as 86 percent of patients treated with more than six pulses of cyclophosphamide responded well to the treatment, compared to only 38 percent in patients receiving only six pulses.

The study also analyzed a number of functional tests, such as FVC, total lung capacity, difficulty in breathing, and the 6-minute walk distance test, but found only a slight improvement in total lung capacity after 12 months.

Adverse events were mainly linked to the immunosuppressive treatment, with mild infections present in seven patients.

Investigators concluded that the therapeutic combination of cyclophosphamide followed by mycophenolate mofetil for 12 months was linked to the stabilization or improvement of pulmonary function in more than half of the systemic sclerosis patients with associated interstitial lung disease analyzed. However, they emphasize that careful disease monitoring is required, and that improvements in care and treatment are still greatly needed.