IL-23 inhibition reduces inflammatory biomarkers in pre-treated UC

Therapy with guselkumab led to an early and consistent reduction of inflammatory biomarkers starting from week 4 through week 12 in patients with ulcerative colitis (UC). A higher percentage of patients treated with guselkumab achieved normalisation of biomarkers at week 12.

The QUASAR induction study 1 (NCT04033445) is a phase 2b study of the IL-23 inhibitor guselkumab (in 2 doses) as induction therapy in patients with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy (e.g. thiopurines or corticosteroids) or advanced therapy (e.g. TNF blockers, vedolizumab, or tofacitinib). Results from the induction phase at week 12 demonstrated that treatment with guselkumab resulted in greater improvements across key clinical and endoscopic/histologic outcome measures compared with placebo [1]. C-reactive protein (CRP) and faecal calprotectin (FCP) are both non-invasive, inflammatory biomarkers indicating disease activity in patients with IBD. Therefore, the influence of guselkumab treatment on these biomarkers was also assessed in the QUASAR study [2].

A total of 313 participants were included in the analysis, 83% had severe disease and 52% had inadequate response to previous therapy. Half of the study population had already failed 1 advanced therapy, mostly TNF blockers, 33.3% had failed 2 advanced therapies.

Median concentrations of both biomarkers were similar across groups (guselkumab 200 mg, guselkumab 400 mg, and placebo) at baseline. Starting from week 4 throughout week 12, greater median reductions in both CRP and FCP concentrations were seen in participants treated with guselkumab compared with placebo: median changes from baseline to week 12 in CRP were -1.86 mg/L for the combined guselkumab group compared with 0.06 mg/L for placebo only (nominal P<0.001). Similarly, FCP concentrations dropped by -684.00 mg/kg at week 12 in the combined guselkumab group compared with 0.00 mg/kg in the placebo group (nominal P<0.001). Consequently, 44% of participants treated with guselkumab achieved normal CRP concentrations (≤3 mg/L) compared with 18.8% in the placebo group (nominal P<0.001). At baseline, median CRP concentrations in the total study population were 5.1 mg/L. The corresponding values for FCP (≤250 mg/kg) were 33.0% versus 9.9% (nominal P<0.001). A dose-dependent effect between the low and high guselkumab dose could not be detected.

1. Panés J, et al. The effect of guselkumab induction therapy in patients with moderately to severely active Ulcerative Colitis: QUASAR phase 2b induction results at week 12 by prior inadequate response or intolerance to advanced therapy. OP109, UEG Week 2022, 8–11 October, Vienna, Austria.
2. Peyrin-Biroulet L, et al. The effect of guselkumab induction therapy on inflammatory biomarkers in patients with moderately to severely active Ulcerative Colitis: QUASAR phase 2b induction results through week 12. MP249, UEG Week 2022, 8-11 October, Vienna, Austria.

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Posted on 1 December 20228 April 2024