Early Use of Triple Combo Seen to Treat Diffuse Cutaneous Scleroderma

A triple combination of prednisolone, cyclophosphamide and plasma exchange (plasmapheresis) was effective against skin thickening in seven of eight people with diffuse cutaneous systemic sclerosis (dcSSc), a case series study reports.

These results support further investigation into treating newly diagnosed dcSSc patients with this combination regimen. The one patient who failed to respond had the longest disease duration.

The study, “Therapeutic efficacy of combined glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis for skin sclerosis in diffuse systemic sclerosis,” was published in the journal Medicine. 

Scleroderma is characterized by the overproduction of collagen, a major component of scar tissue.  

While several immunosuppressive therapies are recommended for people with scleroderma — including prednisolone, methotrexate, cyclophosphamide (brand names, Cytoxan and Neosar), and Cellcept (mycophenolate mofetil, by Genentech), no treatment has been established. 

Prior research reported that low-dose prednisone plus intravenous (directly into the bloodstream) cyclophosphamide eased skin thickness in people with dcSSc. In turn, other studies showed effectiveness in combining immunosuppressive agents with plasmapheresis, a procedure that filters the blood to remove harmful autoantibodies. These self-reacting antibodies are known to contribute to disease progression.

Researchers at the National Center for Global Health and Medicine in Japan wondered if a triple combination therapy using prednisolone, intravenous cyclophosphamide, and double-filtration plasmapheresis would ease skin sclerosis in people with dcSSc. 

To find out, the team examined the medical records of eight patients (six women, two men; mean age of around 56), who were admitted to hospital to treat skin sclerosis between 2008 and 2016. Their mean disease duration was 9.8 months.

All were initially treated with a daily oral dose of 20 to 40 mg of prednisolone, given for two to five weeks before being tapered to 2.5 to 5.0 mg/day. Cyclophosphamide (1 to 2 g) was administered bi-weekly for the treatment duration. All patients also underwent plasmapheresis between two and five times.

Starting dose of prednisolone, and frequency of cyclophosphamide and plasmapheresis were determined by the attending physician based on the severity of skin lesions.

Clinical data were collected before treatment, and then within a week after the final infusion of cyclophosphamide or plasmapheresis.

Comparing baseline (starting) measures to those at end of follow-up (average of 33.5 days), researchers analyzed average change in the modified Rodnan skin score (mRSS, a measure of skin thickness), predicted forced vital capacity (%FVC) — the total amount of air forcibly exhaled from a breath — and predicted carbon monoxide diffusing capacity (%DLCO), which determines how much oxygen travels from the lungs’ air sacs to the bloodstream.

Blood levels of KL-6, a biomarker for scleroderma-related interstitial lung disease, were also assessed.

Results showed that skin thickness scores decreased (eased) significantly from 27.0 at baseline to 15.8 at follow-up. One patient, who began treatment 31 months after disease onset, failed to show improvement. 

Mean %FVC and %DLCO improved moderately, but not with statistical significance at the end of treatment. Levels of KL-6 significantly decreased from 578.9 to 205.3 U/ml. 

No significant correlation was identified across initial skin thickness, disease duration, and mRRS score change. But, the researchers added, the fact that the one person who failed to respond also had the disease for the longest time, indicates that “treatment for skin sclerosis should be initiated during the early disease phase.”

One patient each reported gastroenteritis and chest pain (angina). No kidney problems were reported despite the use of prednisolone.

“Triple therapy may improve skin sclerosis, with effectiveness equal or superior to other reported treatments,” the scientists wrote. “This preliminary case series demonstrates the potential of triple therapy for treating dcSSc.” 

“However, prospective studies with long-term follow-up should be performed to assess its role,” they added.