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

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, MD^9
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, Wks 0, 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.


Disclosures:
Marc Ferrante: AbbVie, Janssen, Pfizer, Takeda – Consultant, Grant/Research Support, Speaker's Bureau. Amgen, Biogen, – Grant/Research Support, Speaker's Bureau. Boehringer Ingelheim, MSD – Consultant, Speaker's Bureau. Celltrion – Consultant. Falk, Ferring – Speaker's Bureau. Lamepro, Mylan, Truvion Healthcare – Speaker's Bureau. Lilly, Medtronic, Thermo Fisher – Consultant. Sandoz – Consultant, Speaker's Bureau.
Valerie Pivorunas: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
James Butler: AbbVie – Stockholder/Ownership Interest (excluding diversified mutual funds), Other Financial or Material Support, Retired employee.
Naim Mahi: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Nael Mostafa: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Melanie Ruzek: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
James Fann: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Feng Hong: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Xiaohong Cao: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Nizar Smaoui: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Justin Wade Davis: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Jasmina Kalabic: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Alexandra Song: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Heath Guay: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Florian Rieder: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Helmsley Charitable Trust, Pliant, Pfizer, UCB – Advisory Committee/Board Member, Consultant, Grant/Research Support. Agomab, Allergan, CDISC, Cowen – Advisory Committee/Board Member, Consultant. Crohn’s and Colitis Foundation, Helmsley Charitable Trust, Kenneth Rainin Foundation – Employee, Grant/Research Support. Crohn’s and Colitis Foundation, Helmsley Charitable Trust, Kenneth Rainin Foundation – Grant/Research Support. Galmed, Genentech, Gilead, Gossamer, Guidepoint – Advisory Committee/Board Member, Consultant. Index Pharma, Jannsen, Koutif, Mestag, Metacrine, Morphic – Advisory Committee/Board Member, Consultant. Organovo, Origo, Prometheus Biosciences, Receptos, RedX, Roche – Advisory Committee/Board Member, Consultant. Samsung, Surmodics, Surrozen – Advisory Committee/Board Member, Consultant. Takeda, Techlab, Theravance, Thetis, UCB, Ysios, 89Bio – Advisory Committee/Board Member, Consultant.
Julian Panés: Abbott, AbbVie, Pfizer – Consultant, Grant/Research Support, Speaker's Bureau. Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltrion – Consultant, Speaker's Bureau. Celgene, Celltrion, Genentech-Roche, GSK – Consultant, Speaker's Bureau. Janssen, Nestle, Orifo, Pandion, Pfizer, Progenity – Consultant, Speaker's Bureau. Takeda, Theravance, Wasserman – Consultant, Speaker's Bureau.
Jean-Frederic Colombel: AbbVie, Takeda – Consultant, Grant/Research Support, Speaker's Bureau. Amgen, Ferring – Consultant, Speaker's Bureau. Arena, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene – Consultant. Galmed Research, Genentech, GSK, Imedex, Immunic, Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support. Janssen, Kaleido Biosciences, Lilly, Merck, Microba – Consultant. Novartis, PBM Capital, Pfizer – Consultant. Sanofi, Takeda, TiGenix and Vifor – Stockholder/Ownership Interest (excluding diversified mutual funds). Sanofi, Takeda, TiGenix, Vifor – Consultant. Shire – Speaker's Bureau.


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. 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, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.