ATHENS, GREECE—About 10% to 15% of people with systemic sclerosis (SSc) develop severe lung disease during the course of their illnesses. One of the most serious pulmonary complications in SSc patients is interstitial lung disease.

Therapy with immunosuppressive drugs such as cyclophosphamide (CP) is usually initiated early in the disease in an attempt to reduce alveolar inflammation and prevent fibrosis.

Because oral CP use is associated with severe adverse reactions, many experts recommend intravenous (IV) pulse administration.

A question that has remained unclear is whether the addition of low- or high-dose prednisolone to IV pulse CP would further improve outcome in patients with SSc interstitial lung disease. Recently, Panayiotis Vlachoyiannopoulos, MD, Assistant Professor of Medicine (Immunology), and colleagues from the National University of Athens School of Medicine conducted a phase II study as a way to begin answering this question.1 Their results, although preliminary, suggest that the combination of IV pulse CP and high-dose prednisolone reduces inflammation, increases forced vital capacity (FVC), and has few severe side effects.

Twenty-eight patients, all of whom received both IV pulse CP and prednisolone, were studied for one year. The first month, they were given 500 mg/m2 of CP, then 750 mg/m2 (to a maximum of 1,500 mg/m2) once a month for the next six months; the 750-mg/m2 dose was then administered every other month for the following six months.

In addition, 12 patients were given prednisolone throughout the study, but no more than 10 mg was administered each day. The other 16 patients were initially administered a daily prednisolone dose of 1 mg/kg (not to exceed 60 mg/d) for four weeks, after which the dose was decreased by 5 mg every other day for two weeks.

The primary end point was improvement seen on high-resolution computed tomographic (CT) scans. Secondary end points included changes in dyspnea severity, pulmonary function test results, and extent of skin involvement.

HIGH-DOSE GROUP SHOWS IMPROVEMENT

After one year, no improvement was seen in the low-dose prednisolone group in the primary or secondary end points. However, the high-dose group showed significant improvements in pulmonary function (especially FVC), skin score, and CT findings, with an average 60% reduction in ground-glass lung involvement and a better interstitial disease score.

Therapy was well tolerated in both groups, with no occurrence of serious side effects. The most common reactions, nausea and vomiting, were easily controlled with antiemetics.

In an interview with PULMONARY REVIEWS, Dr. Vlachoyiannopoulos noted that CP and prednisolone may have a synergistic effect. He added, “If this is the case, our regimen is useful at an early stage of SSc [lung disease] when inflammation is evident.”

He acknowledged, however, that his study’s findings are limited by the small sample size and the fact the patients in the low-dose group had the irreversible component of lung disease (fibrosis) to a greater extent. Thus, larger, long-term, controlled studies are needed to clarify the use of CP plus high-dose prednisolone, as well as the efficacy of each drug alone.

—Gale Jurasek

Reference
1. Pakas I, Ioannidis JPA, Malagari K, et al. Cyclophosphamide with low or high dose prednisolone for systemic sclerosis lung disease. J Rheumatol. 2002;29:298-304.

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