Efficacy and safety of 24-week therapy with a monoclonal antibody to TRBV9+ T lymphocytes (seniprutug) in patients with ankylosing spondylitis: real-world data

In April 2024, the first biologic agent (seniprutug) selectively targeting CD8+ T lymphocytes bearing the TRBV9 segment was approved. This novel mechanism of action potentially affects the initial immunopathologic cascade in HLA-B27-associated ankylosing spondylitis (AS). During 2024, seniprutug therapy was initiated in 9 patients with AS in the European part of Russia.
Objective. To evaluate the efficacy and safety of seniprutug in patients with AS at 12 and 24 weeks (3 and 6 months) in real-world clinical practice.
Material and methods. Nine patients with AS were included: 7 men (77.8%) and 2 women (22.2%); mean age 37.3±12.6 years. AS was diagnosed according to ASAS (2009) and the modified New York criteria (1984). Active sacroiliitis on magnetic resonance imaging (MRI) was present in 8 patients (88.9%); spondylitis in at least one spinal segment in 7 (77.8%), with bone-marrow edema (MRI-confirmed spondylitis) in 6 (66.7%). Baseline disease activity was high: Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.83±0.53; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 5.7±2.01; inflammatory markers were elevated: C-reactive protein (CRP) 49.6±36.7 mg/L (>5 mg/L in 8 patients) and erythrocyte sedimentation rate (ESR) 56.4±28.5 mm/h (>15 mm/h in all patients). Intravenous seniprutug infusions were administered at weeks 0 and 12. Complete 12- and 24-week follow-up data were available for all 9 patients by September 2025.
Results and discussion. At week 12, 8 from 9 patients reported subjective improvement. Mean activity scores decreased: ASDAS to 2.57±0.94 and BASDAI to 3.41±1.17. CRP and ESR declined to 26.79±46.35 mg/L and 25.7±29 mm/h, respectively; normalization of laboratory indices occurred in 55.6% of patients. Low disease activity by ASDAS and BASDAI was recorded in 33.3% and 77.8% of cases, respectively. At week 24, 8 of 9 patients (88.9%) achieved ASAS40 response; mean ASDAS was 1.59±0.21 and BASDAI 1.75±0.81. Mean reductions were ΔASDAS (weeks 0–24) 2.42±0.75 and ΔBASDAI (weeks 0–24) 4.24±2.0. In all patients completing follow-up, inflammatory markers markedly decreased (CRP 3.4±2.3 mg/L; ESR 11.6±7.2 mm/h). One non-responder was switched to an alternative biologic DMARD.
Conclusion. This first real-world study demonstrates significant clinical and laboratory improvement in AS patients treated with seniprutug. The 24-week data support the potential of this approach to modulate the pathogenic cascade in HLA-B27-associated AS and justify further evaluation in larger cohorts.

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