Rituximab May Alleviate Calcinosis Symptoms in Some Scleroderma Patients, Small Study Shows

Treatment with rituximab may help improve the clinical symptoms of calcinosis — the formation of calcium deposits in the skin and muscle — of systemic sclerosis (SSc) patients, a small study suggests.

The study, “Effectiveness and safety of rituximab for the treatment of refractory systemic sclerosis associated calcinosis: A case series and systematic review of the literature,” was published in the journal Autoimmunity Reviews.

Approximately one in every four patients with SSc are at risk of having calcium depositing in the skin and muscles, a complication resulting in skin ulceration, inflammation, and significant pain.

No therapy is yet available for SSc-associated calcinosis, with the only intervention being surgical excision of the calcium deposits, which is an invasive procedure, and relief is short term.

“New therapeutic options with greater efficacy are clearly needed to manage these patients’ illness properly,” the researchers wrote.

Rituximab (sold under the brand name Rituxan in the U.S., and MabThera in Europe, and other countries) is a monoclonal antibody against immune B-cells. As B-cells are important mediators of the underlying mechanism that leads to SSc development, the use of rituximab has become an attractive option for patients with evidence suggesting it may halt skin thickening and lung fibrosis progression.

Some case reports have also suggested that rituximab has a therapeutic action against calcinosis.

To test the effectiveness of rituximab in SSc patients with calcinosis, the researchers analyzed 8 patients, with a mean age of 53 years, who had refractory SSc-related calcinosis in a preliminary study. All patients were given rituximab off-label (as rituximab is not an approved therapy for this medical condition), delivered intravenously twice (on day 1 and 14). Further cycles were repeated on clinical relapse.

In total, patients received a median average of three cycles of rituximab for a median duration of 9 months. Patients were followed for 19 months on average.

All patients had been treated previously with several medicines, such as diltiazem, colchicine, non-steroidal anti-inflammatory drugs, bisphosphonates, and surgery, but without success.

Hands were the most affected (87.5% of lesions) by calcinosis, followed by limbs (forearms, elbows, and/or knees, which were affected in 50% of the cases), and feet (12.5%).

Results showed that half (4) of the patients responded to rituximab treatment, and experienced a significant improvement in clinical symptoms — pain was reduced by at least 50 percent, and they had no new signs of local inflammation or skin ulceration. In two of these patients, the calcifications were completely resolved or significantly reduced in size, as shown on X-rays.

In the other half of the patients, rituximab had no significant clinical effect in relieving calcinosis.

The frequency of side effects was low; only one patient developed upper-respiratory tract infections, and there were no cases of severe infusion reactions or hematological abnormalities.

Researchers also performed a systemic review of reports on SSc-related calcinosis treated with rituximab. Out of six studies, reporting a total of 11 cases, a significant clinical improvement in calcinosis, either partially or completely, was reported in 45.5% of the cases (5 out of 11).

“Our results, and those previously reported, suggest that RTX (rituximab) may be helpful in some patients with SSc-related calcinosis,” the researchers wrote, noting that “these positive data remain preliminary and need to be interpreted with caution.”

The team emphasized that “further randomized clinical studies with large sample sizes are clearly needed to confirm these preliminary open-label data and to establish the correct dose, therapy length and appropriate use of concomitant medications as well as to identify predictors of response to this treatment.”