POS1119 PERIPHERAL BLOOD IMMUNOPHENOTYPE OF PATIENTS WITH SLE IN MAINTENANCE PHASE WHO WERE ABLE TO DISCONTINUE GLUCOCORTICOIDS AFTER INTERVENTION WITH BELIMUMAB: LOOPS REGISTRY, FLOW STUDY
Authors: Y. Miyazaki, S. Nakayamada, S. Kubo, H. Tanaka, K. Hanami, S. Fukuyo, I. Miyagawa, Y. Todoroki, Y. Inoue, Y. Satoh-Kanda, M. Ueno, Y. Tanaka
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> It is unclear as to which SLE patients respond favorably to belimumab (BEL), and the impact of such treatment on peripheral blood immunophenotype in this population remains unknown. <h3>Objectives:</h3> This study aimed to clarify peripheral immunophenotype of patients with SLE who successfully discontinued glucocorticoids (GC) by intervention with BEL in the maintenance phase. <h3>Methods:</h3> Patients with SLE (n=146), who were in the maintenance therapy phase with a SELENA-SLEDAI score of less than 10 and receiving glucocorticoid therapy at a prednisolone-equivalent dose of 0.2 mg/kg/day or less, were assessed. They were divided into the standard of care (SoC) group (46 patients who received hydroxychloroquine or mycophenolate mofetil) and the BEL group (100 patients who received BEL with SoC). The efficacy of BEL group was compared with SoC group after adjustment by propensity score-based inverse probability of treatment weighting (PS-IPTW). Based on the standard human immune cell subset classification protocol by NIH/FOCIS, peripheral immunophenotypes were analyzed in BEL group and SoC group, and were compared. <h3>Results:</h3> After PS-IPTW adjustment, no differences in patient characteristics were shown between the SoC and BEL groups. The retention rate of BEL at 52w was 98.0%. SELENA-SLEDAI scores improved after 52w in both groups. The BEL group also had significantly lower GC doses at 52w (p=0.0028) and 31.8% of the BEL group successfully discontinued GC, whereas on 2.1% of the SoC group did (p=0.0043). The incidence of infections was significantly lower in the BEL group compared to the SoC group before PS-IPTW (BEL, 4.0% vs. SoC, 17.5%, p=0.089). The baseline peripheral immunophenotypes were similar between the two groups. In the BEL group, the proportion of activated T follicular helper cells (p=0.0073), IgD-CD27-B (DNB) cells (p=0.0088) and plasmocytes (p=0.0092) decreased significantly at 26w. There were no significant changes in the SoC group. At 26 weeks, the proportion of DNB cells (p=0.0328) and plasmocytes (p=0.0415) was significantly lower in patients who discontinued glucocorticoids (GCs) compared to those who were unable to discontinue them. Multiple logistic regression analysis showed that GC discontinuation was associated with low GC doses, low SLEDAI scores at BEL initiation, decreased IgG levels at 52w, and a low percentage of DNB cells and plasmocytes at 26w. Of those who discontinued GCs in the BEL group, 81.3% (6/26) did not experience a flare-up of SLE one year after discontinuation. In peripheral blood immunophenotyping six months after discontinuation of GC, the proportion of DN Bcells and plasmocytes was increased in patients who relapsed after discontinuation of GC. On the other hand, the proportion of DN Bcells and plasmocytes did not change in those who did not relapse after discontinuation of GC. <h3>Conclusion:</h3> Intervention with BEL in patients with SLE reduced DNB cells and plasmocytes, thereby controlling the disease activity and enabling GC discontinuation. Among patients who received low GC doses and had low SLEDAI scores, those with decreased IgG levels at 52w successfully discontinued GCs. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Yusuke Miyazaki Y. Miyazaki has received lecture fees from AstraZeneca, GlaxoSmithKline, Astellas, Eli Lilly., Shingo Nakayamada: None declared, Satoshi Kubo Satoshi Kubo has received speaking fees from Eli Lilly, GlaxoSmithKline, Bristol-Myers, Abbvie, Eisai, Pfizer, Astra-Zeneca and also research grants from Daiichi-Sankyo, Abbvie, Boehringer Ingelheim, and Astellas., Hiroaki Tanaka: None declared, Kentaro Hanami: None declared, Shunsuke Fukuyo: None declared, Ippei Miyagawa: None declared, Yasuyuki Todoroki: None declared, Yoshino Inoue: None declared, Yurie Satoh-Kanda: None declared, Masanobu Ueno: None declared, Yoshiya Tanaka Y. Tanaka has received Speakers bureau from Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho., Y. Tanaka has received Grant/research support from Mitsubishi-Tanabe, Eisai, Chugai, Taisho.