Telitacicept Outperforms Belimumab in 24-Week Active SLE Cohort
Key Takeaways
- Among biologic-naive patients with active SLE at one Chinese center, weighted low-disease-activity attainment favored telitacicept over belimumab.
- SRI-4 responses favored telitacicept at both assessments, with statistically significant differences.
- Patients above the prednisone target at baseline more often reached ≤7.5 mg/day with telitacicept, but the ≤5 mg/day contrast was not significant.
- Documented adverse events occurred in 8.7% of telitacicept recipients versus 6.7% of belimumab recipients, with no severe events reported.
At the Affiliated Hospital of Nantong University in China, Shao and colleagues' retrospective cohort in Frontiers in Immunology included 91 biologic-naive patients with active SLE treated from July 2021 through June 2024. Telitacicept was given to 46 patients and belimumab to 45, each alongside conventional therapy; all completed 24-week assessment without switching or rescue treatment. Eligibility required persistent activity with anti–double-stranded DNA positivity, low complement, and a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of at least 8, or active lupus nephritis. Treatment selection reflected affordability, dosing convenience, duration preference, and physician judgment, not randomization. The primary endpoint was low lupus disease activity state (LLDAS) at week 24; secondary endpoints included Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at weeks 12 and 24 and prednisone targets. Inverse probability of treatment weighting (IPTW) accounted for age, sex, baseline SLEDAI-2K, physician global assessment, and British Isles Lupus Assessment Group scores.
At week 24, IPTW-weighted LLDAS attainment was 31% with telitacicept versus 11% with belimumab (P=0.026). Weighted SRI-4 response was 81% versus 47%, respectively. Additional adjustment for residual sex and baseline immunosuppressant imbalance retained the LLDAS association.
At week 12, weighted SRI-4 response was 40% with telitacicept versus 12% with belimumab; differences at both assessments were statistically significant. Among patients above the relevant prednisone target at baseline, 43% versus 20% reached ≤7.5 mg/day by week 24 (P=0.03). Attainment of ≤5 mg/day and absolute prednisone-dose change did not differ significantly. SLEDAI-2K improved more with telitacicept at both assessments, but changes in complement, immunoglobulins, and anti–double-stranded DNA antibodies did not differ significantly. Few adverse events were documented; infections occurred in both groups, without severe events or adverse-event-related discontinuations.
Treatment selection was nonrandom, and sex and baseline immunosuppressant use remained imbalanced after weighting, leaving potential residual confounding despite further adjustment. Five patients who stopped or switched for economic reasons had no post-treatment assessment and were excluded; the findings concern included completers, not everyone starting a biologic. The small, single-center Chinese cohort and short follow-up limit generalizability and longer-term interpretation. Sparse adverse events were not formally compared and cannot establish equivalent or superior safety.
According to the authors, telitacicept was associated with higher weighted LLDAS and SRI-4 responses than belimumab among included patients with active SLE. Prednisone findings depended on the threshold and eligible denominator. Larger prospective randomized studies are needed to confirm the associations, the investigators said.
Clinician Questions
What criteria define low lupus disease activity state in active SLE?
LLDAS requires SLEDAI-2K ≤4 without major-organ or new disease activity, physician global assessment ≤1, prednisone ≤7.5 mg/day, and stable maintenance immunosuppressive therapy. It is a composite clinical state, not a stand-alone kidney response.
How do telitacicept and belimumab differ in their B-cell targets for systemic lupus erythematosus?
Belimumab neutralizes soluble B-lymphocyte stimulator (BLyS/BAFF); telitacicept is a TACI-Fc fusion protein that binds both BLyS and APRIL. These mechanisms were not shown to cause the observed outcome differences.
Did telitacicept show better kidney-specific outcomes than belimumab in lupus nephritis?
In the Chinese cohort's exploratory lupus-nephritis subgroup, composite LLDAS and SRI-4 outcomes favored telitacicept, but complete and partial renal responses and measured urinary protein did not differ significantly. Better composite disease control did not establish superior kidney-specific efficacy.