OP35 Effect of maintenance ustekinumab on corticosteroid-free endoscopic and clinical outcomes in patients with Crohn's Disease - Week 48 analysis of the STARDUST trial

Danese, S.(1);Vermeire, S.(2);D’Haens, G.(3);Panés, J.(4);Dignass, A.(5);Magro, F.(6,7);Nazar, M.(8);Le Bars, M.(9);Lahaye, M.(10);Ni, L.(11);Bravatà, I.(12);Gaya, D.R.(13);Peyrin-Biroulet, L.(14)

(1)Humanitas University, IBD Center, Milan, Italy;(2)University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium;(3)University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands;(4)Hospital Clinic of Barcelona- IDIBAPS- CIBERehd, Department of Gastroenterology, Barcelona, Spain;(5)Agaplesion Markus Hospital, Department of Medicine I, Frankfurt/Main, Germany;(6)Institute for Molecular and Cell Biology- Faculty of Medicine University of Porto, Department of Pharmacology & Therapeutics, Porto, Portugal;(7)Hospital de São João, Department of Gastroenterology, Porto, Portugal;(8)Janssen-Cilag Polska Sp. z .o.o., Medical Affairs, Warsaw, Poland;(9)Janssen-Cilag, Medical Affairs, Issy-les-Moulineaux, France;(10)Janssen-Cilag BV, Medical Affairs, Breda, The Netherlands;(11)Janssen Cilag Russia, Medical Affairs, Moscow, Russian Federation;(12)Janssen-Cilag, Medical Affairs, Milan, Italy;(13)Glasgow Royal Infirmary, Department of Gastroenterology, Glasgow, United Kingdom;(14)University Hospital of Nancy- University of Lorraine, INSERM Unité 954 and Department of Hepato-Gastroenterology, Houdemont, France

Background

The STARDUST study demonstrated that ustekinumab (UST), using either a treat-to-target (T2T) or standard of care (SoC) strategy, may induce and maintain endoscopic and clinical response and remission in Crohn’s disease (CD). Primary endpoint, safety, and efficacy have been reported previously.1 Because corticosteroid (CS) sparing is an important aim of CD management, we compared the efficacy of UST T2T vs SoC in achieving CS-free clinical remission and endoscopic response.

Methods

Adult patients (pts) with moderate–severely active CD who were CDAI 70 responders after 16 weeks (W) of induction, comprising a single dose of UST 6 mg/kg iv followed by UST 90 mg SC at W8, were randomized to either T2T or SoC arms. In the T2T arm, choice of UST maintenance dosage (q12w or q8w) was based on endoscopic improvement at W16, followed by clinical and biomarker-directed dose escalation up to q4w; in the SoC arm, UST q12w or q8w dosage was based on EU SmPC. Primary endpoint was endoscopic response (Simple Endoscopic Score in CD [SES-CD] decrease from baseline [BL] ≥50%) at W48. For pts on CS at W16, CS tapering was mandatory. At W48, CS-free clinical remission (CDAI <150 and no CS for ≥30 days) and CS-free endoscopic response (reduction from BL in SES-CD ≥50% and no CS for ≥30 days) were evaluated.

Results

Of 500 pts enrolled, 441 achieved a CDAI 70 response at W16 and were randomized to T2T (n=220) or SoC (n=221); 79.1% and 87.3%, respectively, completed W48. Among clinical remitters and responders at W16 (start of CS tapering), in both T2T and SoC arms more than 70% were still in remission or response at W48 (Figure 1). CS use throughout 48 weeks of treatment is summarized in Table 1. At W48, in T2T and SoC arms similar rates were noted for CS-free endoscopic response (33.6% and 28.5%, respectively) and CS-free clinical remission (56.4% and 63.3%, respectively). Notably, in T2T and SoC arms the CS-free clinical remission rate among pts on CS at BL was 44.1% and 45.1%, respectively (Figure 2). Among W48 endoscopic responders (T2T, n=83; SoC, n=66), CS-free endoscopic response rate was 89.2% and 95.5%, respectively; among W48 clinical remitters (T2T, n=135; SoC, n=154), CS-free clinical remission rate was 91.9% and 90.9%, in T2T and SoC arms, respectively.


Conclusion

Pts treated with UST under T2T or SoC strategies achieved similar rates of CS-free clinical remission and endoscopic response over 48 weeks. Overall for pts on CS at BL, UST reduced the need for CS while achieving response/remission. Most (>89%) pts with endoscopic response/clinical remission at W48 were also CS-free responders/remitters.  

1. Danese S, et al. United European Gastroenterol J. 2020;8:1264–1265 (Abstract LB11).