P1593 - A Higher Induction Dosing Regimen of Adalimumab Does Not Enhance Modulation of Downstream Blood Molecular Markers in Patients With Moderately to Severely Active Crohn’s Disease or Ulcerative Colitis
AbbVie Bioresearch Center Worcester, MA, United States
Marc Ferrante, MD1, Valerie Pivorunas, PhD2, James Butler, PhD3, Naim Mahi, PhD3, Nael Mostafa, PhD3, Melanie Ruzek, PhD2, James Fann, PhD2, Feng Hong, PhD2, Xiaohong Cao, PhD4, Nizar Smaoui, PhD3, Justin Wade Davis, PhD3, Jasmina Kalabic, PhD5, Alexandra Song, PhD6, Heath Guay, PhD2, Florian Rieder, MD7, Julian Panés, MD, PhD8, Jean-Frederic Colombel, MD9 1University Hospitals Leuven, Leuven, Luxembourg, Belgium; 2AbbVie Bioresearch Center, Worcester, MA; 3AbbVie Inc., North Chicago, IL; 4AbbVie Cambridge Research Center, Cambridge, MA; 5AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Nordrhein-Westfalen, Germany; 6AbbVie, Inc., North Chicago, IL; 7Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH; 8Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain; 9Icahn School of Medicine at Mount Sinai, New York, NY
Introduction: We report proteomic and transcriptomic analyses for adalimumab (ADA) higher induction dosing regimen (HIR) and standard induction dosing regimen (SIR) in patients (pts) with moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC).
Methods: In SERENE-CD and SERENE-UC, pts were randomized to ADA HIR(160mg, Wks0, 1, 2, and 3) or SIR(160mg, Wk0 and 80mg Wk2) then 40mg EOW from wk4 onwards. In SERENE-CD, co-primary endpoints were proportion of pts achieving clinical remission (CR [Crohn’s Disease Activity Index < 150]) at Wk4, and endoscopic response (decrease in Simplified Endoscopic Score for Crohn’s Disease [SES-CD] >50% from baseline [BL] or, if BL SES-CD=4, ≥2-point reduction from BL) at Wk12. Primary endpoint in SERENE-UC was proportion of pts achieving CR(Full Mayo score≤2 with no subscore >1) at Wk8. ADA trough serum concentrations were measured at Wks2, 4, 8, 12(SERENE-CD) and Wks2, 4,8(SERENE-UC). Biomarker analyses on population subset included monitoring modulation of 184 serum proteins(Olink Inflammation and Immune response panels) and 23 additional plasma proteins that showed changes in other ADA indications. Analyses compared BL to Wk12 (SERENE-CD) or Wk8 (SERENE-UC), including OSM, TREM1, IL-6, TNFa, and IFNg markers. A two-sample t-test compared Wk8 (SERENE-UC) or Wk12 (SERENE-CD) change from BL. Changes in whole blood gene expression were evaluated.
Results: SERENE-CD included 270/514 pts (HIR: 124; SIR: 116). SERENE-UC included 194/851 pts (HIR: 117; SIR: 77). BL demographics were generally well balanced across groups. ADA trough serum concentrations were higher in HIR vs SIR groups throughout induction period in both studies. Changes in serum protein levels from BL to Wk12 (SERENE-CD) or Wk8 (SERENE-UC) across a panel of 207 immunomodulatory proteins of interest were not significantly different between dosing regimens in either study. Changes in circulating TNF levels from BL to Wk12 (SERENE-CD) or Wk8 (SERENE-UC) were not significantly different with HIR in either study. No significantly differentially expressed genes were found in whole blood between dosing regimens in either study, indicating no evidence of enhanced gene modulation with HIR.
Discussion: HIR resulted in increased ADA serum concentration vs SIR in both SERENE-CD and SERENE-UC, but this did not translate into increased efficacy of induction treatment. HIR did not influence peripheral blood molecular markers at the gene/ protein level at clinical and endoscopic endpoints vs SIR.