Guselkumab is a selective IL-23 antagonist that binds to p19.1 The double-blind phase 2 GALAXI 1 study evaluated 3 doses of guselkumab vs ustekinumab or placebo in patients with moderately to severely active CD.2,3 During the 12-week induction period, patients randomized to the guselkumab arm received 200, 600, or 1200 mg of guselkumab at weeks 0, 4, and 8. For the maintenance and long-term extension (LTE) studies, 100 or 200 mg of guselkumab was administered every 4 or 8 weeks. At week 12 of induction, 34% of the patients treated with guselkumab (63/185) and approximately 33% of those treated with ustekinumab (21/63) had failed to achieve a CDAI response. Compared with the 185 patients who received guselkumab at any dose, those who failed to achieve a response to induction therapy with guselkumab tended to have a longer duration of CD (11.1 vs 9.3 years), and a greater proportion of them had failed treatment with a biologic therapy (60.3% vs 54.6%). By week 48 of maintenance in the subgroup of induction nonresponders, 58.7% of the patients receiving guselkumab and 47.6% of those receiving ustekinumab had achieved a clinical response (Figure 5), and the rate of clinical remission was 41.3% with guselkumab vs 33.3% with ustekinumab. Among the induction nonresponders in the combined guselkumab subgroups vs the ustekinumab subgroup, the rates of remission based on patient-reported outcomes (PROs) were 42.9% vs 23.8%, and the rates of endoscopic response were 31.7% vs 23.8%.
Figure 5.
Clinical responsea among induction nonresponders at week 12 from a post hoc analysis of the GALAXI 1 study.
aClinical response: ≥100-point reduction from BL in CDAI or CDAI <150.
BL, baseline; CDAI, Crohn’s Disease Activity Index; GUS, guselkumab; UST, ustekinumab.
Adapted from Panaccione et al. Abstract 69. Presented at: ACG 2023; October 20-25, 2023; Vancouver, British Columbia, Canada.2
The GALAXI 1 trial included an LTE study to assess clinical, endoscopic, and safety outcomes.4 The LTE study included 151 patients treated with guselkumab and 48 treated with ustekinumab. Nonresponder imputation was used to account for missing patient data. At week 144, the rate of clinical remission with guselkumab was 95.4% among patients in the LTE observed population and 54.1% in the overall study population; the rate of clinical remission with ustekinumab was 83.8% among patients in the LTE study and 46.0% among all randomized patients. At week 144, rates of endoscopic response were generally maintained with guselkumab (73.5% among observed LTE patients, 34.7% among all randomized patients) and with ustekinumab (41.4% among observed LTE patients, 19.4% among all randomized patients). Rates of endoscopic remission at week 144 with guselkumab were 49.4% in the observed LTE population and 23.3% among all randomized patients; with ustekinumab, the rates were 27.6% in the observed LTE population and 12.9% among all randomized patients. Rates of PRO-2 remission were 89.8% in the observed LTE population and 51.4% among all randomized patients with guselkumab and were 75.7% in the observed LTE population and 39.7% among all randomized patients with ustekinumab. No new safety signals arose. Most infections were not serious; rates of discontinuation, serious AEs, and serious infections were generally low throughout the LTE.
ABSTRACT SUMMARY Comparative Efficacy and Safety of Adalimumab vs Vedolizumab in Managing Moderate-to-Severe Crohn’s Disease: A Systematic Review and Meta-analysis
A systematic review and meta-analysis compared safety and efficacy outcomes in patients with CD (Abstract P0764). For the ability to achieve remissions during induction, the analysis showed a significant benefit with adalimumab (odds ratio [OR], 3.037; P=.000) or vedolizumab (OR, 2.444; P=.000). Similarly, for the induction of response, placebo was inferior to adalimumab (OR, 2.601; P=.000) or vedolizumab (OR, 2.254; P=.000). In addition, the rate of remissions was lower with placebo maintenance than with adalimumab (OR, 4.808; P=.000) or vedolizumab (OR, 2.014; P=.000). The rate of serious AEs was significantly higher with adalimumab than with placebo (OR, 0.514; P=.000), but the difference in the proportions of serious AEs was not significant in a comparison of vedolizumab vs placebo (OR, 1.284; P=.076).
References
- Verstockt B, Salas A, Sands BE et al. Alimentiv Translational Research Consortium (ATRC). IL-12 and IL-23 pathway inhibition in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2023;20(7):433–446. doi: 10.1038/s41575-023-00768-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Panaccione R, Afzali A, D’Haens GR Efficacy of guselkumab in patients with moderately to severely active Crohn’s disease not in clinical response at week 12: results from the GALAXI 1 study. Abstract 69. 2023. Presented at: ACG 2023 Annual Scientific Meeting; October 20-25. Vancouver, Canada.
- Sandborn WJ, D’Haens GR, Reinisch W et al. Guselkumab for the treatment of Crohn’s disease: induction results from the phase 2 GALAXI-1 study. Gastroenterol. 2022;162(6):1650–1664.e1658. doi: 10.1053/j.gastro.2022.01.047. [DOI] [PubMed] [Google Scholar]
- Afzali A, Danese S, Panaccione R Efficacy and safety of guselkumab for Crohn’s disease through 3 years: GALAXI-1 long-term extension. Abstract P0674. 2023. Presented at: ACG 2023 Annual Scientific Meeting; October 20-25. Vancouver, Canada.