BLyS/APRIL dual inhibition for systemic sclerosis: a single-centre, single-arm, open-label clinical trial of telitacicept

OBJECTIVES: We aimed to explore the potential effectiveness and safety of telitacicept in the treatment of systemic sclerosis (SSc) and to investigate mechanisms such as B cell immune phenotypes. METHODS: This was a single-centre, single-arm, open-label study enrolling eight SSc patients inadequately responding to traditional immunosuppressants. All patients received telitacicept 160 mg weekly for 24 weeks in addition to their original stable immunosuppressive background treatment. The primary endpoint was changes in the median modified Rodnan skin thickness score (mRSS) at week 24. RESULTS: This study demonstrated that significant improvements were observed in the primary endpoints. Compared with the mean mRSS (18.9±5.8) at baseline, mRSS declined to 12.5±5.0 (p=0.008) and 10.8±5.8 (p=0.003) at weeks 12 and 24, respectively. SCTC-DI score, ScleroID questionnaire score, and SF-36 physical score at week 24 also improved (p<0.05). The CRISS score was 0.75, indicating clinical improvement, with higher scores reflecting better outcomes. Telitacicept as an add-on treatment significantly decreased CD19+ B cells from 10.2% to 4.3% (p=0.006), decreased transitional B cells from 6.8% to 1.4 % (p=0.005), decreased naive B cells from 8.9% to 3.0% (p=0.001), and increased immature B cells from 0.10 % to 0.24% (p=0.03). Telitacicept add-on treatment also decreased serum levels of immunoglobulins (IgG, IgA, IgM) (p<0.05) at week 24 and increased haemoglobin (p=0.013) at week 12. HRCT score for pulmonary fibrosis showed a decline at week 24 (p=0.036). A decrease in titer of SSc-specific antibodies was observed in six out of eight patients. No serious adverse events occurred. Adverse effects were mainly hypogammaglobulinemia, respiratory tract infection, urinary tract infections, and rash. No deaths occurred. CONCLUSIONS: Telitacicept has the potential to be a safe and effective treatment for patients with SSc; however, further studies with larger sample sizes are needed to confirm these findings and to better understand long-term safety and efficacy.