The following article is a part of conference coverage from the Digestive Disease Week 2021 Annual Meeting , held virtually from May 21 to 23, 2021. The team at Gastroenterology Advisor will be reporting on the latest news and research conducted by leading experts in gastroenterology. Check back for more from DDW 2021.
Among patients with Crohn disease who received 48 weeks of maintenance therapy with ustekinumab, a numerically higher proportion in the treat-to-target (T2T) group achieved a higher endoscopic response compared with those who received standard of care (SoC), according to research presented at Digestive Disease Week 2021.
The phase 3b randomized STARDUST trial compared a T2T maintenance strategy with SoC in patients with Crohn disease treated with ustekinumab. Endoscopy was used at week 16 to guide dose escalation. Researchers reported the endoscopic and clinical results at week 48.
The study included adults with moderate to severely active Crohn disease who failed conventional therapy with at least 1 biologic. Participants received intravenous, weight-based ustekinumab of about 6 mg/kg at baseline, followed by 90 mg of subcutaneous (SC) ustekinumab at week 8.
At week 16, patients whose Crohn Disease Activity Index (CDAI) decreased by ≥70 were randomized 1:1 to the T2T or SoC arm. Participants in the T2T group received SC ustekinumab every 12 weeks or 8 weeks based on 25% improvement in the Simple Endoscopic Score for Crohn Disease (SES-CD) compared with baseline.
From weeks 16 to 48, the ustekinumab dose was increased to every 4 weeks if the following targets were unmet: CDAI <220 and ≥70-point improvement from baseline, and C-reactive protein (CRP) ≤10 mg/L or fecal calprotectin (FCal) ≤250 µg/g. Participants discontinued if they failed the treatment target on ustekinumab every 4 weeks.
Endoscopic response at week 48 (≥50% decrease in SES-CD score compared with baseline on centrally read endoscopies) was the primary endpoint. For missing variables, the study authors used nonresponder imputation (NRI) and last observation carried forward (LOCF).
A total of 441 patients received either T2T (n = 220) or SoC (n = 221); 79.1% and 87.3%, respectively, completed the study to week 48. A numerically higher proportion of patients in the T2T group compared with the SoC arm achieved the primary endpoint: 37.7% vs 29.9%, respectively (P =.0933; NRI). A sensitivity analysis showed that the difference was significant: 40.0% vs 30.8%, respectively (P =.0494; LOCF).
At week 48, high rates of clinical responses were observed in the T2T and SoC groups (NRI/LOCF), respectively: 68.2% vs 77.8% (P =.0212)/89.5% vs 89.6% (nonsignificant [NS]); clinical remission 61.4% vs 69.7%, (NS)/76.8% vs 78.3% (NS); improvement of ≥50% in FCal 39.4% vs 46.5%, (NS)/63.1% vs 60.6% (NS); and CRP levels 41.7% vs 53.3% (P =.032)/53.2% vs 57.2% (NS).
In the T2T and SoC groups, respectively, 59.2% (122/206) and 53.2% (116/218) of participants were started on a regimen of ustekinumab at every 12 weeks. Of these, 59.8% (73/122) and 63.8% (74/116) remained on a dosing schedule of every 12 weeks until week 48.
Of those who were started on a dosing schedule of every 8 weeks, 40.5% (34/84) and 78.4% (80/102) remained on this regimen until week 48 in the T2T and SoC arms, respectively. At week 48, 17% (35/206) of participants were receiving ustekinumab every 4 weeks in the T2T arm. No new safety signals were observed.
“T2T could be an additional tool for physicians to guide ustekinumab dosing decisions in Crohn disease,” stated the study authors. “Overall, high clinical remission and biomarker responses with ustekinumab were achieved in both arms with ustekinumab at week 48.”
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Danese S, Vermeire S, D’Haens GR, et al. Clinical and endoscopic response to treat-to-target versus standard of care in Crohn’s disease patients treated with ustekinumab: week 48 results of the STARDUST trial. Presented at: Digestive Disease Week Annual Meeting; May 21-23, 2021. Abstract 105.