Rituximab improves long-term skin, lung outcomes in systemic sclerosis

Rituximab was associated with significant improvements in both skin and lung parameters over long-term follow-up in a cohort of patients with systemic sclerosis, according to a study.

“Rituximab is emerging as a promising therapeutic option for systemic sclerosis (SSc), but its long-term outcomes and response markers are unknown,” Ai Kuzumi, MD, PhD, of the department of dermatology at University of Tokyo Graduate School of Medicine, and colleagues wrote.

In addition to assessing long-term outcomes associated with rituximab use in SSc, the researchers also aimed to identify potential markers of response to the drug in a single-center cohort study.

The study population was culled from the 43 patients with SSc who completed the 48-week DESIRES trial, in which rituximab was associated with skin sclerosis improvement. Of these 43 patients, 31 patients continued to be treated with rituximab through 96 weeks. Twenty-nine patients (median age, 48 years; interquartile range [IQR], 35-45; 27 women) had complete data for post-hoc analysis of clinical and laboratory findings.

Outcomes were assessed using the modified Rodnan skin score (MRSS) and percentage of predicted forced vital capacity (FVC%).

After one course of rituximab, the median change in MRSS overall was 7 (IQR, 8.5 to 4; P < .001). After three courses of the drug, the median change in FVC% was 1.85 (IQR, 0.13-5.68; P < .001). These responses were sustained through follow-up, according to the findings.

The researchers also observed 16 so-called “high responders” to rituximab, defined by an MRSS improvement of at least 9. These patients experienced a greater decrease in serum immunoglobulin G (IgG) levels (median change in IgG, 125; IQR, 207 to 83 vs. median change in IgG, 7; IQR, 120 to 43; P = .008) compared with this response in the 13 low responders, defined as a response of 8 or less. In addition, the high responders also reported a greater decrease in serum IgA levels compared with low responders (IgA, 45; IQR, 96 to 32 vs. IGA, 11; IQR, 20 to 3; P < .001).

Moreover, a Spearman correlation test found a decrease in serum IgA levels demonstrated a significant association with improvement in MRSS (r = 0.64; P < .001).

Findings from the final follow-up visit showed that seven patients demonstrated low IgM, whereas one patient each demonstrated low IgA and IgG. Low IgM carried a significant association with improvement in FVC% (median change in FVC% predicted, 7.2; IQR, 3.8-8.9 vs. 3.6; IQR, 1.4-6.2; P = .003).

“In this cohort study, rituximab treatment was associated with significantly improved skin and lung fibrosis in SSc in a long-term follow-up,” Kuzumi and colleagues concluded. “Decrease in serum immunoglobulins was associated with greater clinical response.”