Impact of the extraarticular manifestations on the efficacy and tolerability of seniprutug in radiographic axial spondyloarthritis: post hoc analysis of ELEFTA clinical trial

Objective: to assess the impact of extra-articular manifestations (EAM) on the achievement of clinical effect of seniprutug (SENI) in patients with active radiographic axial spondyloarthritis (r-axSpA) during 48 weeks of therapy.

Material and methods. A post hoc analysis of results from an international multicenter randomized placebo-controlled phase II clinical trial (CT) BCD-180-2/ELEFTA (ClinicalTrials.gov NCT05445076) involving HLA-B27 positive biologic-naive patients with active r-axSpA was conducted. The main results of the CT ELEFTA on the clinical efficacy and safety of SENI over 48 weeks of therapy have been previously published.

A comparative post hoc analysis of SENI efficacy was conducted at week 48 in subgroups of patients with presence (n=48) and absence (n=212) of EAM, who received SENI at doses of 5 mg/kg or 7 mg/kg or Placebo/SENI 5 mg/kg. Efficacy parameters included dynamics in the ASDAS, BASFI, as well as total back pain intensity and night back pain scores on a numerical rating scale (NRS), and C-reactive protein (CRP) levels. Additionally, the frequency of achieving ASAS40, ASAS5/6 responses, ASDAS clinically important improvement (ASDAS-CII), and low disease activity or inactive disease according to ASDAS was analyzed.

The assessment of treatment tolerability included analysis of the frequency of worsening of existing EAM and the occurrence of cases of EAM de novo.

Results and discussion. In both subgroups of patients with and without EAM of axSpA we observed decrease of CRP level with improvement of the disease activity according to the ASDAS index and improvement of functional impairments according to the BASFI index, as well as achievement of ASAS40 and ASAS5/6 responses and a reduction in of the total back pain and night back pain according to the NRS. Statistically significant superiority over placebo was demonstrated in the SENI subgroup without EAM at all efficacy parameters and at several assessment points in the SENI subgroup with EAM already in the first weeks of therapy and up to week 24. Further, the achieved clinical effect was maintained, up to week 48, in all SENI subgroups regardless of the presence of EAM, while in placebo subgroups, an increase in effect was observed due to switching to active drug therapy at week 24. In the SENI subgroup with EAM, a numerically more pronounced clinical effect was noted at the beginning of therapy without statistically significant differences compared to the SENI subgroup without EAM.

In all studied subgroups, a favorable tolerability profile of SENI therapy was demonstrated. No EAM de novo was registered.

Conclusion. SENI demonstrates significant stable clinical efficacy and good tolerability over 48 weeks of active r-axSpA treatment regardless of the presence or absence of EAM, with a trend to faster and more pronounced clinical effect in the first weeks of therapy in patients who had EAM.

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