Telitacicept, a recombinant fusion protein targeting B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), is emerging as a promising therapeutic agent for a range of autoimmune diseases. By inhibiting the interaction of BLyS and APRIL with their receptors on B lymphocytes, telitacicept modulates B-cell maturation, differentiation, and autoantibody production. This dual-target approach has demonstrated clinical benefits in conditions such as systemic lupus erythematosus (SLE), lupus nephritis (LN), primary Sjogren’s syndrome (pSS), and rheumatoid arthritis (RA).
Mechanism of Action and Pharmacokinetics
Telitacicept functions by binding to the specific soluble extracellular portion of TACI, a receptor with a strong affinity for both BLyS and APRIL. This action inhibits the further development and maturation of immature B lymphocytes by blocking BLyS and inhibits the differentiation of mature B lymphocytes into plasma cells by blocking APRIL. The recommended dose is 160 mg via subcutaneous injection once a week. Pharmacokinetic studies indicate that telitacicept follows a two-compartment target-mediated pharmacokinetic model, with a clearance half-life of 19.8 days for total serum telitacicept and 11.7 days for free serum telitacicept.
Systemic Lupus Erythematosus (SLE)
Clinical trials have demonstrated the efficacy of telitacicept in treating SLE. A Phase IIb clinical trial (C005SLECLLI) showed that the SLE Response Index (SRI4) response rate at week 48 was significantly higher in the telitacicept groups compared to the placebo group. Specifically, the risk of serious recurrence at week 52 was reduced by 55.8% in the telitacicept 80mg group (HR = 0.442), by 55.5% in the 160mg group (HR = 0.445) at week 52, and by 72.0% in the telitacicept 240mg group (HR = 0.280). A Phase III clinical study in China further confirmed these findings, with an 82.6% SRI4 response rate in the telitacicept 160 mg group compared to 38.1% in the placebo group (P < 0.001) at week 52. A real-world study also supported these results, showing an overall SRI-4 response rate of 80% with telitacicept treatment.
Lupus Nephritis (LN)
Telitacicept has also shown promise in treating lupus nephritis, a severe complication of SLE. Studies have indicated that telitacicept increases the renal response rate and improves renal function in patients with SLE-LN. A Phase IIb clinical study demonstrated a significantly higher renal response rate in the telitacicept groups compared to the placebo group from week 4, with significant improvement in renal involvement at week 52. In a Phase III clinical study, the telitacicept 160 mg group showed a more pronounced reduction in 24-h urine protein levels compared to placebo.
Primary Sjogren’s Syndrome (pSS)
In a Phase II clinical trial involving 42 pSS patients, telitacicept (160 mg and 240 mg) administered once a week for 24 weeks resulted in significantly lower ESSDAI scores compared to placebo (P < 0.05). The change values from baseline in the ESSDAI scores in the telitacicept 160 mg, 240 mg and placebo groups were −4.0, −3.1, and −0.2 points, respectively. Salivary and lacrimal function also improved to varying degrees in the telitacicept group compared to the placebo group. A Phase III clinical trial is currently underway in China to further evaluate the efficacy and safety of telitacicept in patients with active pSS (NCT05673993).
Rheumatoid Arthritis (RA)
A Phase III clinical trial (NCT03016013) assessing the efficacy and safety of telitacicept in RA patients with inadequate response to methotrexate showed that the ACR20 response rate at week 24 was significantly higher in the telitacicept group compared to the placebo group (60.0% vs 26.9%, P < 0.001). The telitacicept group also had a significantly higher ACR50 response rate (21.4% vs 5.9%, P < 0.001) and a lower DAS28-ESR from baseline compared to the placebo group. Radiographic joint damage was also significantly reduced in the telitacicept group.
Other Autoimmune Diseases
Telitacicept is being explored as a treatment for other autoimmune diseases, including IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), myasthenia gravis (MG), autoimmune nodopathies (AN), IgA nephropathy (IgAN), idiopathic membranous nephropathy (IMN), and minimal-change glomerulonephritis (MCD). Early studies and case reports suggest potential benefits in these conditions, warranting further investigation.
Safety and Tolerability
Telitacicept generally exhibits a favorable safety profile. Infections are the most commonly reported adverse effect. In a study involving Chinese patients with RA, telitacicept at subcutaneous doses up to 540 mg showed a favorable safety and tolerability profile, with mild to moderate infections and transient injection site reactions being more common than in patients receiving placebo. While no adverse events related to progressive multifocal leukoencephalopathy (PML) have been reported in telitacicept clinical trials, clinicians should remain vigilant and discontinue treatment if clinical signs of PML arise.
Future Directions
Telitacicept represents a promising therapeutic option for a range of autoimmune diseases. Ongoing and future clinical trials will further elucidate its efficacy and safety profile, optimize dosing strategies, and identify biomarkers to predict treatment response. Further research is also needed to determine the optimal timing for initiating telitacicept therapy and to assess the safety of reducing or discontinuing other immunosuppressive medications during telitacicept treatment.
