The efficacy and safety of divozilimab in patient with systemic sclerosis: 48-week results of the randomized double-blind placebo-controlled phase III clinical study LIBERIUS

The aim of the study is to evaluate the efficacy, safety and immunogenicity of divozilimab (DIV), anti-CD20 monoclonal antibody, in patients with systemic sclerosis (SS). Materials and methods . Patients with SS according to ACR/EULAR (American College of Rheumatology/ European Alliance of Associations for Rheumatology) 2013 criteria with modified Rodnan skin score (mRSS) ≥10 and ≲20 and forced vital capacity (FVC) ≥40% from the due took part in the study. Infusions of DIV 250 mg were administered on weeks 0 and 2, and DIV 500 mg – on week 24 with the subsequent use in open mode, starting from week 48. This publication presents data obtained for 48 weeks of trial (before the DIV infusion at week 48). Primary endpoint was the change in the mRSS from baseline to week 48. The dynamic of FVC was estimated as the secondary endpoint. The safety evaluation included the frequency and profile of adverse events and adverse reactions (ARs). Immunogenicity was assessed by detection of binding and neutralizing anti-drug antibodies on weeks 2, 24 and 48. Results . 151 patients were randomized into two groups: DIV ( n =76) and Placebo ( n =75). The most were female; the median duration of the disease was about 3–4 years. The initial value of the mRSS was 14 and 13 points in DIV and PBO groups, respectively. The change of mRSS from baseline to week 48 was –5.8±1.1 points in DIV group and –2.7±1.0 points in Placebo group (adjusted mean difference (AMD) with 95% confidence interval –3.1 (–4.5; –1.7); p <0.0001). The lung function was stable in patients treated with DIV. A comparable safety profile of DIV and PBO was demonstrated. The most frequent ARs were infusion reactions and a decrease in the number of lymphocytes. There were no severe and serious ARs in DIV group. All infusion reactions were mild and moderate. 5.3% (4/76) patients in DIV group had binding antibodies without neutralizing activity. Conclusion . Divosilimab has demonstrated a significant decrease in severity of skin fibrosis, a positive effect on the respiratory function and a favorable safety profile, which allows to consider it as a promising therapeutic option for SS.

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Publication Details

Journal
Rheumatology Science and Practice
Published
2025-05-01
DOI
https://doi.org/10.47360/1995-4484-2025-158-167
Citations
2
Primary Topic
Systemic Sclerosis and Related Diseases
Type
article
Field-Weighted Citation Impact
2.94
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article

The efficacy and safety of divozilimab in patient with systemic sclerosis: 48-week results of the randomized double-blind placebo-controlled phase III clinical study LIBERIUS

О. Р. Зиганшин, Т. В. Кропотина, L. P. Ananyeva, Т. В. Поварова et al.
2 citations
Rheumatology Science and Practice
Systemic Sclerosis and Related Diseases
2.94
article

The efficacy and safety of divozilimab in patient with systemic sclerosis: 48-week results of the randomized double-blind placebo-controlled phase III clinical study LIBERIUS

О. Р. Зиганшин, Т. В. Кропотина, L. P. Ananyeva, Т. В. Поварова, А. В. Еремеева, D. G. Krechikova, I. Z. Gaydukova, A. A. Porozova, E. A. Fokina, I. B. Vinogradova, L. V. Ivanova, О. Н. Аношенкова, Д. И. Абдулганиева, G. Lukina, Yulia Linkova, Е. В. Зонова, A. A. Lutckii, L. V. Eliseeva, О. Б. Ершова, N. E. Nikulenkova, M. V. Zlobin, N. Soroka, M. Starovoytova, П. С. Пухтинская, Е. С. Жугрова, A. V. Zinkina-Orikhan, G. F. Fatkhullina, T. V. Plaksina, O. B. Nesmeyanova, Yu. Yu. Grabovetskaya
article en
2 citations

Abstract

The aim of the study is to evaluate the efficacy, safety and immunogenicity of divozilimab (DIV), anti-CD20 monoclonal antibody, in patients with systemic sclerosis (SS). Materials and methods . Patients with SS according to ACR/EULAR (American College of Rheumatology/ European Alliance of Associations for Rheumatology) 2013 criteria with modified Rodnan skin score (mRSS) ≥10 and ≲20 and forced vital capacity (FVC) ≥40% from the due took part in the study. Infusions of DIV 250 mg were administered on weeks 0 and 2, and DIV 500 mg – on week 24 with the subsequent use in open mode, starting from week 48. This publication presents data obtained for 48 weeks of trial (before the DIV infusion at week 48). Primary endpoint was the change in the mRSS from baseline to week 48. The dynamic of FVC was estimated as the secondary endpoint. The safety evaluation included the frequency and profile of adverse events and adverse reactions (ARs). Immunogenicity was assessed by detection of binding and neutralizing anti-drug antibodies on weeks 2, 24 and 48. Results . 151 patients were randomized into two groups: DIV ( n =76) and Placebo ( n =75). The most were female; the median duration of the disease was about 3–4 years. The initial value of the mRSS was 14 and 13 points in DIV and PBO groups, respectively. The change of mRSS from baseline to week 48 was –5.8±1.1 points in DIV group and –2.7±1.0 points in Placebo group (adjusted mean difference (AMD) with 95% confidence interval –3.1 (–4.5; –1.7); p <0.0001). The lung function was stable in patients treated with DIV. A comparable safety profile of DIV and PBO was demonstrated. The most frequent ARs were infusion reactions and a decrease in the number of lymphocytes. There were no severe and serious ARs in DIV group. All infusion reactions were mild and moderate. 5.3% (4/76) patients in DIV group had binding antibodies without neutralizing activity. Conclusion . Divosilimab has demonstrated a significant decrease in severity of skin fibrosis, a positive effect on the respiratory function and a favorable safety profile, which allows to consider it as a promising therapeutic option for SS.

Rheumatology Science and PracticeVol. 63(2)
Novosibirsk State Medical University (RU), Immanuel Kant Baltic Federal University (RU), Kazan State Medical University (RU), Siberian State Medical University (RU), Moscow Clinical Scientific Center (RU), Nizhny Novgorod Regional Clinical Hospital named after Semashko (RU), Regional Clinical Hospital No 4 (RU), Ulyanovsk Regional Clinical Hospital (RU), Biomed Research Institute (US), Izhevsk State Medical Academy (RU), Budgetary Healthcare Institution of Omsk Region Regional Clinical Hospital (RU), Chelyabinsk Regional Clinical Oncology Center (RU), North-Western State Medical University named after I.I. Mechnikov (RU), BIOCAD (Russia) (RU), Republican Scientific and Practical Center of Neurology and Neurosurgery (BY), Saratov City Clinical Hospital № 2 named. IN AND. Razumovsky (RU), Republican Clinical Hospital named after G.G. Kuvatova (RU)
Openalex Percentile: Top 10%
Systemic Sclerosis and Related Diseases
2.94
DOIOpen Access PDFOpenAlex
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