Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease

Shi, Fan; Xue, Ran; Zhou, Xuexiao; Shen, Pei; Wang, Shengzhi; Yang, Yun

doi:10.1080/08923973.2021.1973493

Cited by 65 publications

(61 citation statements)

References 31 publications

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“…[15][16][17] Ongoing clinical trials involving telitacicept/ RC18 include SLE, IgA nephropathy, Antiphospholipid syndrome, Rheumatoid arthritis, Multiple sclerosis, Myasthenia Gravis, Primary Sjögren's Syndrome, and Neuromyelitis Optica Spectrum Disorders, of which all subjects were older than 18 years. 18,19 Case 1 was unable to tolerate adverse reactions of glucocorticoids and refused to use glucocorticoids, Case 2 was due to overweight (106 kg), and Case 3 was because of persistent low platelets, concerning about glucocorticoids side effects and affordability, 160 mg per week were used on these three patients. Cases 1-3 were from Children's Hospital of Fudan University.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of telitacicept in refractory childhood-onset systemic lupus erythematosus: A self-controlled before–after trial

Sun

Shen

Gong

et al. 2022

Lupus

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Objective To observe the efficacy and safety of telitacicept in refractory childhood-onset systemic lupus erythematosus (cSLE). Methods A self-controlled before–after trial. Children with active SLE, aged 5–18 years, who cannot tolerate side effects of glucocorticoid, were enrolled in our study. Patients received subcutaneous injection of telitacicept weekly based on the standard treatment. SLE responder index-4 (SRI-4) was assessed before the first administration and at least 4 weeks after the first administration. Results Among the 15 cases of refractory cSLE, three were males (20%) and 12 were females (80%). The median age and weight were 13 years old and 52 kg, respectively. The median duration of disease was 30 months. 5–26 weeks (80 or 160 mg per week) after administration of telitacicept, 66.7% ( n=10) reached SRI-4 response. 12 cases reduced their glucocorticoid intake from 40 mg/d to 17.5 mg/d. The urinary protein after treatment declined in 8 cases whose 24-h proteinuria was >0.5 g at baseline. The urinary protein in two of the eight cases turned negative and plasma albumin in five of the eight cases rose to normal. In addition, three of these eight cases demonstrated varying degrees of improvement in renal impairment, whose estimated glomerular filtration rate (eGFR, ml/min·1.73 m2) rose from 17.4 to 26.6, 40.7 to 48.2, and 63.2 to 146.0, respectively. There were mild to moderate adverse events after treatment. Conclusion Telitacicept combined with the standard treatment may significantly increase the SRI-4 response rate and reduce the glucocorticoid dosage in refractory cSLE, and also shown efficacy on lupus nephritis. The related adverse drug events were controllable.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of telitacicept in refractory childhood-onset systemic lupus erythematosus: A self-controlled before–after trial

Sun

Shen

Gong

et al. 2022

Lupus

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“…As a B cell depletion therapy, ianalumab has 2 modes of action: B-cell lysis by enhanced ADCC and blockade of BAFF signaling. Telitacicept, a TACI-Ig fusion protein, is also under clinical development based on its inhibitory effect on the BAFF/APRIL system ( 94 ).…”

Section: Cell-targeted Therapymentioning

confidence: 99%

Targeted Immunotherapy for Autoimmune Disease

Jung

Kim

2022

Immune Netw

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In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.

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“…Telitacicept is a new type of TACI-Fc fusion protein that has a new drug structure and a double-target mechanism. It can inhibit both BLyS and APRIL cytokines simultaneously, thereby reducing the immune response more effectively and achieving the purpose of treating autoimmune diseases [56]. At present, clinical trials of telitacicept in the treatment of moderate and severe RA have been conducted, and the indications are expected to be further expanded.…”

Section: Monoclonal Antibody Therapy Targeting Cytokinesmentioning

confidence: 99%

Trends of Treatment Development in Rheumatoid Arthritis: Promise, Progress, and Challenges

Jiang¹,

Wei²,

Zhao³

et al. 2022

Preprint

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Rheumatoid arthritis (RA) is a chronic, systemic, abnormal inflammatory immune response. It is characterized by the involvement of the synovium and multiple organs and the destruction of joints and articular cartilage. In the past 30 years, several promising novel compounds and antibodies have been developed for the treatment of RA. The introduction of new drugs and precision medicine for all forms of RA raises several issues related to access to novel treatments by patients, optical regimen selection, cost-effectiveness, prognosis monitoring and outcome surveillance, particularly with regard to the development of low drug response rates, drug resistance and adverse side effects. Tremendous attention has been given to the identification of optimized drug combinations for the treatment of RA, particularly in early high-risk vulnerable and early individuals. Addressing these issues requires novel therapeutic approaches with new mechanisms and the establishment of accurate guidelines for drug selection, drug recombination, and non-chemical therapeutic efforts. In this study, we reviewed the most exciting recently established or ongoing novel drugs and approaches according to the clinical trial database maintained by the United States National Library of Medicine and discussed the trends in RA drug development and challenges in the treatment, providing a reference significant for the accurate treatment of RA and the research direction in the future.

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Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease

Cited by 65 publications

References 31 publications

Safety and efficacy of telitacicept in refractory childhood-onset systemic lupus erythematosus: A self-controlled before–after trial

Safety and efficacy of telitacicept in refractory childhood-onset systemic lupus erythematosus: A self-controlled before–after trial

Targeted Immunotherapy for Autoimmune Disease

Trends of Treatment Development in Rheumatoid Arthritis: Promise, Progress, and Challenges

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