Some dcSSC Patients’ Skin Issues Returned after Reducing or Ending CellCept, Study Says

Some dcSSC Patients’ Skin Issues Returned after Reducing or Ending CellCept, Study Says

A subgroup of patients with rapidly progressive diffuse cutaneous scleroderma (dcSSc) experienced a relapse of skin manifestations shortly after stopping or lowering the dose of CellCept (mycophenolate mofetil), according to a five-year study.

The findings also showed rapid improvements after restarting CellCept, and revealed that patients with faster disease progression and on a higher CellCept dose were more prone to relapse.

The research, “Recurrence of progressive skin involvement following discontinuation or dose reduction of Mycophenolate Mofetil treatment in patients with diffuse Systemic Sclerosis,” was published in the journal Seminars in Arthritis and Rheumatism.

Genentech’s CellCept is an immunosuppressant that inhibits the differentiation of fibroblasts into myofibroblasts, and thereby may ease fibrosis (scarring). In patients with rapidly progressive dcSSc, CellCept has shown the ability to halt disease worsening and its associated pulmonary manifestations. The therapy is therefore often used to treat SSc-related skin involvement and interstitial lung disease (ILD).

Despite these benefits, the optimal duration of treatment with CellCept is unknown.

A team at Thomas Jefferson University addressed this issue by conducting a five-year follow-up study in 19 patients (mean age 50.3 years, 15 women) with rapidly progressive dcSSc, whose disease onset occurred within the last 24 months.

Patients were treated with CellCept (2,000 mg per day) for an average of 22.9 months, and subsequently discontinued or reduced the dose to or below 1,000 mg/day at the end of an open-label study.

No patient had radiological evidence of SSc-associated ILD at study start.

Clinical assessments included the Modified Rodnan skin score (mRSS), and pulmonary function tests, conducted every 3–6 months for five years. Of note, the mRSS assesses skin thickness as a marker of disease severity.

Five patients (26.3%) required a restart of treatment with CellCept, within an average of 6.9 months, as their mRSS increased by at least 20%. One of these patients experienced a relapse after dose reduction, and four after discontinuing the treatment. Two of the patients developed respiratory symptoms with worse pulmonary function scores and evidence of ILD on high-resolution computed tomography.

One other patient had a decline in the diffusing capacity for carbon monoxide — a measure of the lungs’ capacity to transfer oxygen from the air sacs into the blood — without suggestion of pulmonary arterial hypertension.

All these five patients showed a return to baseline or rapid stabilization of their skin manifestations after restarting CellCept treatment. The two patients who had developed restrictive lung disease also experienced an improvement in their pulmonary function tests.

The group experiencing relapses was found to have digital ulcers more frequently (80% vs. 21.05%), were treated with a higher dose of CellCept (2,600 vs. 2,000 mg/day), and showed faster disease progression before starting on the therapy compared with non-relapsing patients (9.6 vs. 15.7 months).

No differences were seen between the two groups in clinical manifestations or laboratory tests associated with more active disease, including increased erythrocyte sedimentation rate and elevated serum levels of C-reactive protein — two indicators of inflammation — or the presence of pulmonary hypertension.

The data further showed that the initial severity of skin manifestations did not significantly correlate with the occurrence of relapse. Still, patients with digital ulcers were more likely to relapse.

Two patients in the non-relapsing group also needed to restart treatment with CellCept after more than two years because of slowly progressive development of ILD.

Based on the results, the team concluded that the “findings confirm the therapeutic benefit of [CellCept] in [rapidly progressive] dcSSc, and suggest that [CellCept] treatment should be maintained for longer than two years.”

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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