The impact of clinical and demographic factors on the efficacy of divozilimab in patients with systemic sclerosis: Post hoc analysis of the randomized, double-blind, placebo-controlled phase III clinical trial LIBERIUS

Divozilimab (DIV) is a new monoclonal antibody drug against CD20, which has demonstrated efficacy and safety in patients with systemic sclerosis (SS) in terms of reducing skin fibrosis and stabilizing lung function.

The aim of the study was to assess the dynamics of skin fibrosis according to the mRSS in SSD patients treated DIV with depending on gender, disease duration and initial lung function.

Material and methods. A post hoc analysis of data from a 48-week randomized placebo-controlled phase III clinical trial BCD-132-5/LIBERIUS was conducted. 151 patients with SS were randomized into groups treated with DIV (n=76) or Placebo (n=75). DIV was administered intravenously at 250 mg on weeks 0 and 2, and then at 500 mg once every 24 weeks. The efficacy of DIV compared to placebo in terms of reducing skin fibrosis according to the mRSS was evaluated in subgroups of patients formed by gender (female/male), disease duration at the time of therapy initiation (less than 3 years, from 3 to 5 years, and more than 5 years), as well as by initial lung function (forced vital capacity (FVC) % predicted ≥80%/<80%).

Results. The average change in mRSS from baseline at week 48 in men was –6.1±2.1 in the DIV and 1.6±6.2 in Placebo (LS mean difference (LSMD) –7.5 (95% CI: –11.6; –3.4); p=0.0004). In the subgroup of women, the change in mRSS was –5.1±4.1 and –2.5±4.4 in the DIV and Placebo groups respectively (LSMD=–2.5 (95% CI: –4.0; –1.0); p=0.001).

In patients with a SS duration of up to 3 years, the mRSS dynamics was the most pronounced: –5.6±4.0 in DIV compared to –0.7±6.0 in placebo (LSMD=–5.2 (95% CI: –7.4; –2.9); p<0.0001). In the other subgroups, mRSS dynamics were numerically higher under DIV treatment compared to placebo: –5.2±3.5 and –2.2±2.9 (LSMD=–2.6 (95% CI: –5.5; 0.3); p=0.078) in the subgroup with SS duration of 3 to 5 years and –5.0±4.2 and –3.4±3.8 (LSMD=–1.2 (95% CI: –3.5; 1.0); p=0.285) in patients with a disease duration of more than 5 years.

DIV demonstrated a significant effect in the subgroup with initially normal lung function, where mRSS dynamics was –5.4±3.5 in DIV and –2.4±4.2 in placebo (LSMD=–2.8 (95% CI: –4.4; –1.2), p=0.0008), as well as in patients with initial FVC<80% of predicted, where mRSS reduction was –4.9±4.6 and –0.1±7.0 in DIV and in placebo respectively (LSMD=–5.5 (95% CI: –8.6; –2.4); p=0.0006).

A statistically significant difference in mRSS dynamics was found between male and female subgroups (p=0.024) and a trend toward higher efficacy in patients with disease duration of less than 3 years compared to subgroups with a SS duration of 3 to 5 years and more than 5 years (p=0.056). No differences in DIV efficacy were found between subgroups of patients with initially normal and reduced lung function (p=0.133).

Conclusion. DIV is a promising and effective therapeutic option for all patients with SS, regardless of gender, although a more pronounced effect on reducing skin fibrosis can be expected in men. DIV therapy is appropriate at any SS duration, but the highest efficacy in terms of skin fibrosis is observed in patients with recently developed disease. A significant and marked reduction in skin score in patients with initially normal and reduced lung function defines the possibility of DIV therapy in a broad population of SS patients. This is promising for improving the visceral lesions prognosis during DIV therapy, especially in the case of early therapy.

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