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 . 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 .
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.
- 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.
- 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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Table of Contents: UEGW 2022
Letter from the Editor
UEGW 2022 Highlights Podcast
IBD in 2022
Fast recapture of response with ozanimod after withdrawal in UC
Ozanimod treatment prompted substantial response after failure of response to induction
Etrasimod shows advantage over placebo in UC
Etrasimod reduces adaptive immune cells in the periphery in UC
Favourable maintenance rates for risankizumab also in delayed responders with CD
IL-23 inhibition reduces inflammatory biomarkers in pre-treated UC
Maintained symptom control with mirikizumab in UC
Mirikizumab successfully resolves active histologic inflammation in UC
Upadacitinib for CD: remarkable efficacy in induction therapy
Sustained maintenance results with upadacitinib in UC
Start low with brepocitinib and ritlecitinib in UC
Another chance for TYK2 inhibition in UC
Small molecule obefazimod shows promise in UC
Pivotal results of etrolizumab for CD partly disappointing
Better results for vedolizumab in early CD
Some patients with limited CD may benefit from an early surgical intervention
Dose-interval of adalimumab might be prolonged in CD patients in stable remission
What Is Hot in Upper GI Disorders?
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