One-Year Cytoxan Treatment Improves Lung Function in Scleroderma-ILD Patients, Trials Show

Treatment for one year with the immunosuppressant Cytoxan (cyclophosphamide) improves lung function in scleroderma patients with interstitial lung disease (SSc-ILD) — but these benefits wear off after stopping treatment, data from Phase 3 trials show.

The study, “Cyclophosphamide for Systemic Sclerosis-related Interstitial Lung Disease: A Comparison of Scleroderma Lung Study I and II,” was published in the Journal of Rheumatology.

ILD is a common condition among scleroderma patients, and generally involves progressive scarring of lung tissue.

Two clinical trials compared the efficacy of Bristol-Myers Squibb‘s Cytoxan with a placebo, and with Genentech‘s CellCept (mycophenolate mofetil), also an immunosuppressant, in people with SSc-ILD.

The Scleroderma Lung Study (SLS) I (NCT01762449; NCT00004563) investigated the effects of a one-year course of Cytoxan treatment versus placebo on lung function and health-related symptoms. In turn, SLS II (NCT00883129) compared the effects of one-year of Cytoxan followed by one year of placebo versus two years of CellCept treatment.

Prior results of SLS I showed that, while Cytoxan treatment improved lung function compared with placebo, the effects disappeared within one year off therapy. Meanwhile, findings from SLC II suggested that one-year treatment with Cytoxan had a more sustained effect on lung function compared with two years on CellCept.

However, these studies used different analytic approaches — a significant limitation when comparing their results.

To address this gap, researchers at University of California and their colleagues used a unique model to compare efficacy outcomes between the Cytoxan-treated groups in SLS I (79 patients, mean age 48.4 years) and SLS II (69 patients, 52.2 years).

The model evaluates the impact on two lung function measures. The first, forced vital capacity (FVC), corresponds to the amount of air that can be forcibly exhaled after the deepest breath possible. The second, diffusion capacity of the lungs for carbon monoxide (DLCO), measures how much oxygen goes from the lungs’ alveoli — tiny air sacs — to the blood stream.

At baseline, which is the start of each study, patients from both trials had similar FVC (as assessed by % of predicted), and modified Rodnan skin score (mRSS) — a parameter that evaluates skin thickness as a marker of disease severity. However, patients assigned to Cytoxan in SLS I had lower DLCO.

Results showed that FVC increased from month 3 to month 12 in people treated with Cytoxan in both studies. However, no significant FVC improvements were found beyond this point.

At SLS II completion (24 months), FVC% predicted improved by a mean of 2.88% in the Cytoxan group. In contrast, no changes were noticed in SLS I.

Regarding DLCO, researchers found no differences between trials after two years. In SLS I, DLCO actually declined from baseline to 12 months and stabilized thereafter. In SLS II DLCO only appeared to increase in the period between 12 to 21 months.

Higher FVC and DLCO at baseline — meaning better lung function — were found to be associated with more significant improvements in both trials.

The data also revealed that, regardless of scleroderma type, patients treated with Cytoxan showed a steady decline — a sign of improvement — in mRSS over 12 months.

Serious adverse events occurred in 69 individuals, most of which — 72.3% for SLS I, and 73.0% for SLS II — were deemed unrelated to treatment with Cytoxan. In total, 17 patients died, to include 11 in SLS II and six in SLS I.

Overall, the data showed that one-year treatment with Cytoxan improved the patients’ lung function in both SLS I and II studies. However, “the effects were not sustained following cessation” of Cytoxan treatment, the researchers said.

“These findings suggest that alternate safe and effective therapy is still needed for SSc-ILD, and that continued immunosuppression beyond 1 year may be necessary to achieve a sustained treatment response in patients with SSc-ILD,” the team said.