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Intestinal ultrasound response and transmural healing after ustekinumab induction in Crohn’s disease: Week 16 interim analysis of the STARDUST trial substudy
Background/Aims Intestinal ultrasound (IUS) is a non-invasive tool for evaluating transmural disease activity in Crohn’s disease (CD). The STARDUST trial (NCT03107793) IUS substudy assessed changes in IUS parameters. We report interim results (week-16) from including transmural response to ustekinumab (UST) induction therapy.
Methods Adults with moderate to severe active CD (CD activity index [CDAI]: 220–450), simple endoscopic index [SES-CD] ≥ 3) who failed conventional therapy ± 1 biologic, received approximately 6mg/kg UST intravenously at week-0 and 90mg subcutaneously at week-8. At week-16, patients (CDAI reduction≥ 70) were randomized (1:1) to treat-2-target or standard-of-care. Key IUS endpoints assessed at week-4, week-8, and week-16 (central reading) included: IUS response (IUSR;≥ 25 % bowel wall thickness [BWT] reduction from baseline); BWT change from baseline (mm); IUS remission (IUSREM; transmural healing)‒BWT normalization, color Doppler signal≤1, normal echo stratification, and absence inflammatory fat. Correlations/percent agreement between IUSR/IUSREM and clinical response/remission (CDAI70), biomarker (CRP/FCal levels) and endoscopy outcomes (SES-CD scores) were assessed.
Results The IUS substudy enrolled 82/94 patients; n = 76 had baseline and ≥ 1 post baseline IUS assessments. IUSR and IUSREM (transmural healing) rates at week-16 were 33.8 % and 11.3 %, respectively. Most affected segments were ileum (63.5 %) and colon (33.0 %), with better outcomes in colon. BWT and Doppler signal began normalizing at week-8; inflammatory fat and echo stratification at week-16. Mean BWT improvement from baseline was significant at week-4 (p≤0.0002). Moderate agreement was observed between IUS parameters and biomarkers/endoscopic improvement.
Conclusion STARDUST was the first study to use IUS in CD. IUS response to UST was detected as early as week-4, and a clinically meaningful percentage of patients achieved transmural healing, primarily in colon, at week-16, indicating IUS could be a valuable tool to detect early-treatment response. Future studies can confirm whether early IUS response is predictive of long-term outcomes for CD patients.
Article published online:
26 May 2020
© Georg Thieme Verlag KG
Stuttgart · New York