Efficacy and safety of telitacicept in patients with lupus nephritis

Zhu,Hong; Hu,Hui-Qian; Wei,Hui-Ling; Zhang,De-Xin; Yang,Hua; Zhang,Qian-Kun; Jin,Lie

doi:10.3892/etm.2024.12660

Efficacy and safety of telitacicept in patients with lupus nephritis

Authors:
- Hong Zhu
- Hui-Qian Hu
- Hui-Ling Wei
- De-Xin Zhang
- Hua Yang
- Qian-Kun Zhang
- Lie Jin
View Affiliations

Affiliations: Division of Nephrology, Lishui Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou University, Lishui, Zhejiang 323000, P.R. China
Published online on: July 23, 2024 https://doi.org/10.3892/etm.2024.12660
Article Number: 371
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Although telitacicept is a promising drug for treating systemic lupus erythematosus, there are limited studies on its efficacy and safety in patients with lupus nephritis in China. This lack of research data restricts its potential for broader application and acceptance on a global scale. The present study aimed to determine the efficacy and safety of telitacicept in patients with lupus nephritis (LN) in China. Using a self‑controlled before‑after comparison method, patients with LN were recruited at Lishui Central Hospital between February 2022 and April 2023, who received telitacicept weekly as part of the standard treatment. Data on the systemic lupus erythematosus disease activity index 2000 (SLEDAI‑2K), glucocorticoid dosing and the quantity of immunosuppressive medicines prescribed was collected. Additionally, serum complements, erythrocyte sedimentation rate (ESR), urinary protein levels, immunoglobulin concentrations, serum creatinine levels, plasma albumin concentrations, platelet counts and renal function parameters were documented throughout the study. A total of 13 patients were enrolled in the trial, comprising 11 women and two men. Following 12‑48 weeks of treatment with telitacicept (80 or 160 mg per week), 84.6% (n=11) of all patients experienced symptom relief and their SLEDAI‑2K score was reduced by more than four points. By the observation endpoint, the median glucocorticoid dosage of the 13 patients was decreased from 15 to 2.5 mg/d, and six patients discontinued their glucocorticoids. Furthermore, 46.1% of patients (n=6) reduced their dose and number of immunosuppressive medicines, while 15.4% (n=2) stopped their immunosuppressive medicines. Minimal changes were observed in serum creatinine, platelet count, C3 levels and C4 levels among patients. Immunoglobulin levels (IgG, IgA and IgM) remained stable or showed an upward trend. Plasma albumin levels remained within the normal range in three patients and increased in ten patients. It increased to the normal range in three of these ten patients. At the endpoint, ESR levels decreased in all patients. Additionally, three patients displayed varying degrees of renal function improvement, and their estimated glomerular filtration rate (ml/min/l.73 m²) increased from 127.8 to 134.2, 95.1 to 123.1 and 61.5 to 67.3, respectively. Urinary protein levels decreased in all patients. It decreased >0.5 g/l in seven patients and reached the normal levels in three patients. The adverse events of telitacicept were manageable. Among the patients infected with COVID‑19, three patients had fever, 10 patients remained asymptomatic and none of them exhibited severe respiratory syndromes. In this study, telitacicept effectively stabilized LN activity and alleviated the clinical symptoms of most patients. Furthermore, it reduced the dose of glucocorticoid and immunosuppressive medicines. Therefore, telitacicept may be a promising treatment option for individuals with lupus nephritis.

View Figures

View References

1	Mohamed A, Chen Y, Wu H, Liao J, Cheng B and Lu Q: Therapeutic advances in the treatment of SLE. Int Immunopharmacol. 72:218–223. 2019.PubMed/NCBI View Article : Google Scholar
2	Parodis I, Tamirou F and Houssiau FA: Prediction of prognosis and renal outcome in lupus nephritis. Lupus Sci Med. 7(e000389)2020.PubMed/NCBI View Article : Google Scholar
3	Chen Y, Sun J, Zou K, Yang Y and Liu G: Treatment for lupus nephritis: An overview of systematic reviews and meta-analyses. Rheumatol Int. 37:1089–1099. 2017.PubMed/NCBI View Article : Google Scholar
4	Parikh SV, Almaani S, Brodsky S and Rovin BH: Update on lupus nephritis: Core curriculum 2020. Am J Kidney Dis. 76:265–281. 2020.PubMed/NCBI View Article : Google Scholar
5	Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE and Mohan C: Lupus nephritis. Nat Rev Dis Primers. 6(7)2020.PubMed/NCBI View Article : Google Scholar
6	Shiraz AK, Panther EJ and Reilly CM: Altered germinal-center metabolism in B cells in autoimmunity. Metabolites. 12(40)2022.PubMed/NCBI View Article : Google Scholar
7	Rovin BH, Furie R, Teng YKO, Contreras G, Malvar A, Yu X, Ji B, Green Y, Gonzalez-Rivera T, Bass D, et al: A secondary analysis of the Belimumab international study in lupus nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis. Kidney Int. 101:403–413. 2022.PubMed/NCBI View Article : Google Scholar
8	Onuora S: Adding belimumab improves lupus nephritis. Nat Rev Rheumatol. 16(601)2020.PubMed/NCBI View Article : Google Scholar
9	Samy E, Wax S, Huard B, Hess H and Schneider P: Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. Int Rev Immunol. 36:3–19. 2017.PubMed/NCBI View Article : Google Scholar
10	Shi F, Xue R, Zhou X, Shen P, Wang S and Yang Y: Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease. Immunopharmacol Immunotoxicol. 43:666–673. 2021.PubMed/NCBI View Article : Google Scholar
11	Dhillon S: Telitacicept: First approval. Drugs. 81:1671–1675. 2021.PubMed/NCBI View Article : Google Scholar
12	Fan Y, Gao D and Zhang Z: Telitacicept, a novel humanized, recombinant TACI-Fc fusion protein, for the treatment of systemic lupus erythematosus. Drugs Today (Barc). 58:23–32. 2022.PubMed/NCBI View Article : Google Scholar
13	Sun L, Shen Q, Gong Y, Li Y, Lv Q, Liu H, Zhao F, Yu H, Qiu L, Li X, et al: Safety and efficacy of telitacicept in refractory childhood-onset systemic lupus erythematosus: A self-controlled before-after trial. Lupus. 31:998–1006. 2022.PubMed/NCBI View Article : Google Scholar
14	Chen R, Fu R, Lin Z, Huang C and Huang W: The efficacy and safety of telitacicept for the treatment of systemic lupus erythematosus: A real life observational study. Lupus. 32:94–100. 2023.PubMed/NCBI View Article : Google Scholar
15	Aringer M and Petri M: New classification criteria for systemic lupus erythematosus. Curr Opin Rheumatol. 32:590–596. 2020.PubMed/NCBI View Article : Google Scholar
16	Gladman DD, Ibañez D and Urowitz MB: Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 29:288–291. 2022.PubMed/NCBI
17	Computing VARFFS. R: A language and environment for statistical computing. 2020.
18	Kaul A, Gordon C, Crow MK, Touma Z, Urowitz MB, van Vollenhoven R, Ruiz-Irastorza G and Hughes G: . Systemic lupus erythematosus. Nat Rev Dis Primers. 2(16039)2016.PubMed/NCBI View Article : Google Scholar
19	Golder V and Hoi A: Systemic lupus erythematosus: An update. Med J Aust. 206:215–220. 2017.PubMed/NCBI View Article : Google Scholar
20	Houssiau FA and Ginzler EM: Current treatment of lupus nephritis. Lupus. 17:426–430. 2008.PubMed/NCBI View Article : Google Scholar
21	Yusuf IH, Sharma S, Luqmani R and Downes SM: Hydroxychloroquine retinopathy. Eye (Lond). 31:828–845. 2017.PubMed/NCBI View Article : Google Scholar
22	Surówka A, Prowans P, Żołnierczuk M, Miśkiewicz M, Wawrowski T, Skodda M, Markowska M and Kędzierska-Kapuza K: The effect of calcineurin inhibitors on MMPs activity in heart and their side effects-a review of literature. Int J Mol Sci. 24(10291)2023.PubMed/NCBI View Article : Google Scholar
23	Garrity ST, Jung JY, Zambrowski O, Pichi F, Su D, Arya M, Waheed NK, Duker JS, Chetrit Y, Miserocchi E, et al: Early hydroxychloroquine retinopathy: Optical coherence tomography abnormalities preceding Humphrey visual field defects. Br J Ophthalmol. 103:1600–1604. 2019.PubMed/NCBI View Article : Google Scholar
24	Kaye KS, Belley A, Barth P, Lahlou O, Knechtle P, Motta P and Velicitat P: Effect of cefepime/enmetazobactam vs. piperacillin/tazobactam on clinical cure and microbiological eradication in patients with complicated urinary tract infection or acute pyelonephritis: A randomized clinical trial. JAMA. 328:1304–1314. 2022.PubMed/NCBI View Article : Google Scholar
25	Tunnicliffe DJ, Palmer SC, Henderson L, Masson P, Craig JC, Tong A, Singh-Grewal D, Flanc RS, Roberts MA, Webster AC and Strippoli GF: Immunosuppressive treatment for proliferative lupus nephritis. Cochrane Database Syst Rev. 6(CD002922)2018.PubMed/NCBI View Article : Google Scholar
26	Kado R and McCune WJ: Ovarian protection with gonadotropin-releasing hormone agonists during cyclophosphamide therapy in systemic lupus erythematosus. Best Pract Res Clin Obstet Gynaecol. 64:97–106. 2020.PubMed/NCBI View Article : Google Scholar
27	Galiwango PJ, Delgado DH, Yan R, Kozuszko S, Smith R, Rao V and Ross HJ: Mycophenolate mofetil dose reduction for gastrointestinal intolerance is associated with increased rates of rejection in heart transplant patients. J Heart Lung Transplant. 27:72–77. 2008.PubMed/NCBI View Article : Google Scholar
28	Ugarte A, Danza A and Ruiz-Irastorza G: Glucocorticoids and antimalarials in systemic lupus erythematosus: An update and future directions. Curr Opin Rheumatol. 30:482–489. 2018.PubMed/NCBI View Article : Google Scholar
29	Wang L, Li J, Xu D, Fang J, Van Vollenhoven R and Zhang F: OP0137 Efficacy And Safety Of Telitacicept, A Novel Blys/April Dual Inhibitor, In Patients With Systemic Lupus Erythematosus: A phase 3, randomized, placebo-controlled 52-week study. Ann Rheumatic Dis. 82:90–91. 2023.
30	Avasare R, Drexler Y, Caster DJ, Mitrofanova A and Jefferson JA: Management of lupus nephritis: New treatments and updated guidelines. Kidney360. 4:1503–1511. 2023.PubMed/NCBI View Article : Google Scholar
31	Lv J, Liu L, Hao C, Li G, Fu P, Xing G, Zheng H, Chen N, Wang C, Luo P, et al: Randomized phase 2 trial of telitacicept in patients with IgA nephropathy with persistent proteinuria. Kidney Int Rep. 8:499–506. 2022.PubMed/NCBI View Article : Google Scholar
32	Wu D, Li J, Xu D, Merrill JT, van Vollenhoven RF, Liu Y, Hu J, Li Y, Li F, Huang C, et al: Telitacicept in patients with active systemic lupus erythematosus: Results of a phase 2b, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 83:475–487. 2024.PubMed/NCBI View Article : Google Scholar
33	Ji L, Geng Y, Zhang X, Deng X, Song Z, Tan M, Tan Y, Qu C and Zhang Z: B cell pathway dual inhibition for systemic lupus erythematosus: A prospective single-arm cohort study of telitacicept. MedComm. 5(e515)2024.PubMed/NCBI View Article : Google Scholar