OP0306 EFFECTIVENESS OF RITUXIMAB AND TOCILIZUMAB IN MANAGING SKIN FIBROSIS IN PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: S. Kubo, Y. Satoh-Kanda, Y. Todoroki, R. Kanda, H. Tanaka, M. Ueno, Y. Inoue, Y. Miyazaki, I. Miyagawa, K. Hanami, S. Nakayamada, Y. Tanaka
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rituximab and tocilizumab exhibit potential as molecular targeted therapies for skin fibrosis in patients with systemic sclerosis. While rituximab has demonstrated improvement in skin fibrosis in a limited number of double-blind studies, tocilizumab has shown a favorable trend in a larger double-blind study. However, there is insufficient data on the real-world effectiveness of both drugs in daily clinical practice, and prognostic factors remain unclear. <h3>Objectives:</h3> To assess and compare the efficacy of rituximab and tocilizumab in treating skin fibrosis relative to standard of care (SoC), while also investigating the factors influencing the effectiveness of each treatment. <h3>Methods:</h3> In a comparative analysis, 32 patients treated with rituximab alongside SoC, 29 patients receiving tocilizumab with SoC, and 32 patients in the SoC-only group were examined. To mitigate potential selection bias in patient backgrounds across the three groups, propensity score-based inverse probability of treatment weighting was applied. The primary endpoint was the alteration in the modified Rodnan skin score (mRSS) after 24 weeks. Additionally, flow cytometric immune cell profiling, known as the "Human Immunology Project" by NIH/FOCIS, was conducted, and microvascular damages were assessed using nailfold video capillaroscopy. As an exploratory endpoint, we examined peripheral blood immunophenotypic characteristics and the extent of microvascular damages in cases exhibiting improved skin fibrosis. <h3>Results:</h3> The mRSS values were 14.0, 13.1, and 13.5 for the rituximab, tocilizumab, and SoC groups, respectively, with no significant differences among the three groups. Other parameters such as disease duration (7.2, 8.1, and 7.9 years) and age (59.9, 60.7, and 60.2 years) also exhibited no notable differences. After 6 months of treatment, the improvement in skin score was -3.6 points for rituximab, -2.1 points for tocilizumab, and +0.9 points for SoC. Both rituximab and tocilizumab demonstrated significant improvement compared to SoC (p &lt; 0.001, p = 0.005), with no significant difference between rituximab and tocilizumab (p = 0.24) (Figure 1). The analysis of factors contributing to the effectiveness of each drug revealed that neither rituximab nor tocilizumab exhibited a clinical background predictive of efficacy. Peripheral blood immunophenotyping revealed associations between the percentages of effector memory CD4<sup>+</sup> T cells, central memory CD4<sup>+</sup> T cells, Th1, Th17, plasmablasts, and CD16<sup>+</sup> NK cells and improved skin fibrosis at 24 weeks with rituximab. In multivariate analysis, only plasmablasts were inversely correlated with the efficacy of rituximab (p = 0.003) (Table 1). Conversely, no immune cells contributed to predicting the effectiveness of tocilizumab. Nailfold capillaries analysis showed that tocilizumab tended to improve cases with normal or giant capillaries, while those with hemorrhage or loss of capillaries were less likely to improve (p = 0.20). <h3>Conclusion:</h3> Both rituximab and tocilizumab exhibited improvement in skin fibrosis compared to SoC. For rituximab, the immunophenotype may be useful in treatment selection. However, there is no identified indicator for tocilizumab, necessitating further biomarker studies. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Satoshi Kubo has received speaking fees from Eli Lilly, GlaxoSmithKline, Bristol-Myers, Abbvie, Eisai, Pfizer, Astra-Zeneca., has received research grants from Daiichi-Sankyo, Abbvie, Boehringer Ingelheim, and Astellas., Yurie Satoh-Kanda: None declared, Yasuyuki Todoroki: None declared, Ryuichiro Kanda: None declared, Hiroaki Tanaka: None declared, Masanobu Ueno: None declared, Yoshino Inoue: None declared, Yusuke Miyazaki has received speaking fees from Eli Lilly and GlaxoSmithKline., Ippei Miyagawa: None declared, Kentaro Hanami: None declared, Shingo Nakayamada has received speaking fees from Bristol-Myers, UCB, Astellas, Abbvie, Eisai, Pfizer, and Takeda, has received research grants from Mitsubishi-Tanabe, Novartis, and MSD., Yoshiya Tanaka has received speaking fees from Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho., has received research grants from Mitsubishi-Tanabe, Eisai, Chugai, Taisho.