OP0142 EFFICACY AND SAFETY OF TELITACICEPT, A NOVEL BLYS/APRIL DUAL INHIBITOR, IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME: A PHASE 2, RANDOMIZED, PLACEBO-CONTROLLED 24-WEEK STUDY

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; pp. 94 - 95
• Main Authors: Xu, D., Zhang, S., Huang, C., Qin, L., Li, X., Chen, M., Liu, X., Liu, Y., Li, Z., Hu, J., Bao, C., Wei, W., Tian, J., Duan, X., Van Vollenhoven, R., Fang, J., Zeng, X.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2023; Elsevier B.V; Elsevier Limited
• Subjects: Adverse events; APRIL protein; Autoimmune diseases; BLyS protein; CD19 antigen; Clinical Trials; Fc receptors; Fusion protein; Herpes zoster; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Infections; Lymphocytes B; Patients; Placebos; Randomized control trial; Respiratory tract diseases; Safety; Scientific Abstracts; Sjogren's syndrome; Sjögren syndrome; Statistical analysis; Systemic lupus erythematosus; Clinical Trials; Randomized control trial; Sjögren syndrome
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.1728

BackgroundPrimary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by B-cell hyperactivity. There are still currently no systemic treatments approved for pSS. Telitacicept (TACI-Fc fusion protein) is a novel BLyS (B-lymphocyte stimulator)/APRIL (a proliferation-inducing ligand) dual inhibitor, which has been approved in 2021 in China for the treatment of patients with active systemic lupus erythematosus (SLE)[1].ObjectivesTo evaluate the efficacy and safety of telitacicept in patients with pSS.MethodsIn this phase 2, placebo-controlled study, 42 patients with active pSS (ESSDAI score ≥5) were randomized to 3 treatment arms: placebo (N=14), telitacicept 160 mg (N=14) and telitacicept 240 mg (N=14). Study drugs were administered subcutaneously weekly for 24 weeks. The primary endpoint was the change from baseline in the ESSDAI score at week 24. Key secondary endpoints included: ESSPRI, MFI-20, immunological biomarkers including IgG, IgA, IgM and CD19+ B cells. Safety was assessed during the study.ResultsBaseline demographics and disease characteristics were similar among treatment arms. The ESSDAI score and MFI-20 score decreased from baseline through week 24 in telitacicept 160 mg and 240 mg groups (Figure 1A, 1B). Statistically significant improvements were observed for the ESSDAI score and MFI-20 score both at week 12 and week 24 in the telitacicept 160 mg group; statistically significant improvements were observed for the ESSDAI score at week 12 and MFI-20 score at both week 12 and week 24 in the telitacicept 240 mg group (Table 1). Telitacicept treatment produced rapid and sustained reductions in IgG, IgA, IgM and CD19+ B cells (Figure 1C-F). Incidences of treatment-emergent adverse events (TEAEs) were comparable across treatment arms. Most of TEAEs were mild to moderate in severity. Serious adverse events (SAEs) were infrequent and occurred only in the placebo group. Upper respiratory tract infections were the most common infections. (Table 1)Figure 1.Change from baseline in ESSDAI (A) and MFI-20 (B). Percent (%) change from baseline in IgG (C), IgA (D), IgM (E) and CD19+ B cells (F).Table 1.Key efficacy and safety data.Efficacy, FASPlacebo (N=14)Telitacicept 160 mg (N=14)Telitacicept 240 mg (N=14)ESSDAI change from baseline, LS mean (95%CI)Week 120.8(-1.0～2.6)-3.6(-5.4～-1.8)*-2.5(-4.4～-0.5)*Week 240.5(-1.5～2.4)-3.8(-5.7～-2.0)*-2.3(-4.4～-0.2)ESSPRI change from baseline, Mean ±SDWeek 12-0.10±1.859-0.78±1.449-0.55±1.182Week 24-0.76±1.678-1.09±1.597-0.61±1.876MFI-20 change from baseline, Mean ±SDWeek 126.4±6.44-1.5±9.21*-4.8±9.72*Week 247.0±9.35-4.0±10.30*-5.1±8.94*Safety, SSPlacebo (N=14)Telitacicept 160 mg (N=14)Telitacicept 240 mg (N=14)TEAE, n(%)13(92.9%)12(85.7%)14(100.0%)SAE, n(%)1(7.1%)0(0)0(0)Infections and infestations# (SOC), n(%)8(57.1%)9(64.3%)5(35.7%)Upper respiratory tract infections, n(%)7(50.0%)6(42.9%)4(28.6%)Herpes zoster, n(%)1(7.1%)2(14.3%)0(0)Infectious pneumonia, n(%)2(14.3%)0(0)0(0)*p<0.05 vs. Placebo. #AEs occoured in ≥ 2 subjects in any group were listed.FAS, full analysis set; SS, safety set; LS, least square; SD, standard deviation; TEAE, treatment-emergent adverse event; SAE, serious adverse event; SOC, system organ class.ConclusionTelitacicept showed clinical benefits and a favorable safety profile in patients with pSS.Reference[1] Dhillon S. Telitacicept: First Approval. Drugs. 2021 Sep;81(14):1671-1675.AcknowledgementsThe patients and their families who participated in this study.Disclosure of InterestsDong Xu: None declared, Shangzhu Zhang: None declared, Cibo Huang: None declared, Chenghui Huang: None declared, li Qin: None declared, Xiaomei Li: None declared, Meiqing Chen: None declared, Xiumei Liu: None declared, Yi Liu: None declared, ZHIJUN LI: None declared, Jiankang Hu: None declared, Chunde Bao: None declared, Wei WEI: None declared, Jing Tian: None declared, Xinwang Duan: None declared, Ronald van Vollenhoven: None declared, Jianmin Fang Shareholder of: RemeGen Co., Ltd, Employee of: RemeGen Co., Ltd, Xiaofeng Zeng: None declared.