P772 Comprehensive disease control in patients with Ulcerative Colitis: refinement of a multi-component endpoint using data from the filgotinib SELECTION trial

Journal of Crohn s and Colitis, vol. 18, pp. i1430–i1432

Abstract

Abstract Background Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement. We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522). Methods CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP <150 µg/g, CDC4-150; CDC4 with FCP <250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP <150 µg/g, CDC5-150; and CDC5 with FCP<250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was visualized in UpSet plots. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components). Results At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve pMCS remission compared with 5.0%, 10.1% and 6.0% who did not achieve IBDQ remission, biomarker remission and endoscopic improvement, respectively (Figure). Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions. Conclusion CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.

Authors 8

1. Stefan Schreiber

   Christian-Albrechts-Universität zu Kiel · University Hospital Schleswig-Holstein

   Affiliation as printed

   Kiel University- University Hospital Schleswig-Holstein, Department of Internal Medicine I , Kiel,

   Kiel University- University Hospital Schleswig-Holstein, Department of Internal Medicine I, Kiel, Germany

2. Brian G. Feagan

   Western University · London Health Sciences Centre · Alimentiv Inc. (Canada)

   Affiliation as printed

   Alimentiv Inc., Senior Scientific Director , London ON,

   Western University, Division of Gastroenterology- London Health Sciences Centre , London ON,

   Alimentiv Inc., Senior Scientific Director, London ON, Canada

   Western University, Division of Gastroenterology- London Health Sciences Centre, London ON, Canada

3. Severine A.R.A. Vermeire

   Universitair Ziekenhuis Leuven

   Affiliation as printed

   UZ Leuven, Department of Gastroenterology and Hepatology , Leuven,

   UZ Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium

4. Silvio Danese

   Vita-Salute San Raffaele University · IRCCS Ospedale San Raffaele

   Affiliation as printed

   IRCCS Hospital San Raffaele, Department of Gastroenterology and Digestive Endoscopy , Milan,

   Vita-Salute San Raffaele University, Department of Gastroenterology , Milan,

   IRCCS Hospital San Raffaele, Department of Gastroenterology and Digestive Endoscopy, Milan, Italy

   Vita-Salute San Raffaele University, Department of Gastroenterology, Milan, Italy

5. Veerle Vyncke

   Galapagos (Belgium)

   Affiliation as printed

   Galapagos NV, Medical Affairs , Mechelen,

   Galapagos NV, Medical Affairs, Mechelen, Belgium

6. Margaux Faes

   Galapagos (Belgium)

   Affiliation as printed

   Galapagos NV, Biostatistics , Mechelen,

   Galapagos NV, Biostatistics, Mechelen, Belgium

7. Alessandra Faria Oortwijn Aachen Galapagos B.V

   Galapagos (Netherlands)

   Affiliation as printed

   Galapagos B.V., Medical Affairs , Leiden,

   Galapagos B.V., Medical Affairs, Leiden, The Netherlands

8. Laurent Peyrin‐Biroulet

   Inserm · McGill University Health Centre · Centre Hospitalier Régional et Universitaire de Nancy · Nutrition-Génétique et Exposition aux Risques Environnementaux · Université de Lorraine

   Affiliation as printed

   McGill University Health Centre, Division of Gastroenterology and Hepatology , Montreal QC,

   Nancy University Hospital, Department of Gastroenterology , Vandœuvre-lès-Nancy,

   Nancy University Hospital, FHU Curing and Preventing IMID CURE , Vandœuvre-lès-Nancy,

   Nancy University Hospital, INFINY Institute , Vandœuvre-lès-Nancy,

   Paris IBD Center, Ambroise Paré – Hartmann Private Hospital Group , Neuilly-sur-Seine,

   University of Lorraine, Inserm- NGERE , Nancy,

   McGill University Health Centre, Division of Gastroenterology and Hepatology, Montreal QC, Canada