Clinical Benefit of Adalimumab Dose Adjustment for Patients With Moderately to Severely Active Crohn’s Disease in EXTEND (2014)

Introduction: Weekly dosing was shown to have a clinical benefit for adalimumab (ADA)-treated patients with Crohn’s disease enrolled in the clinical trial CHARM, who had flares or lost response to every other week ADA dosing. The clinical outcomes of dose escalation in patients enrolled in the EXTEND trial are evaluated. Methods: EXTEND was a 52-week double-blind (DB) trial in which patients received open-label (OL) ADA 160/80 mg at weeks 0/2. At week 4, patients were randomized to placebo or ADA 40 mg every other week. Patients with flares/non-response could move to OL ADA 40 mg every other week beginning at week 8, followed by escalation to 40 mg weekly for continued flare/non-response. Week 52 clinical remission (CDAI<150), clinical response (decrease in CDAI≥70 from baseline), and mucosal healing (absence of mucosal ulceration) were assessed in patients who moved to and remained on OL ADA every other week and in those who moved to OL ADA every week. Endpoints are reported using nonresponder imputation (NRI) for patients with missing data and as observed for patients remaining in the study at week 52. Logistic regression analysis was used to determine predictors of moving to OL every week ADA. Results: In EXTEND, 42.2% (27/64) of patients randomized to DB ADA moved to OL ADA, and 23.4% (15/64) escalated to every week dosing. The only significant predictor of dose escalation was week 4 nonresponse (odds ratio 24.2; 95% CI 1.6, 365.2; p=0.021). Week 52 outcomes for patients who completed the study on OL ADA (every other week or every week) are shown in the table. Increased adverse event rates were not observed with OL every week dosing. Conclusion: Escalation to weekly ADA dosing demonstrated clinical benefit in patients who met protocol criteria for dose escalation. No new safety risks were observed with every week ADA dosing. Disclosure - J-F Colombel reports having served as consultant, advisory board member or speaker for AbbVie, Bristol Meyers Squibb, Ferring, Genentech, Giuliani SPA, Given Imaging, Merck & Co., Millenium Pharmaceuticals Inc., Pfizer Inc. Prometheus Laboratories, Sanofi, Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma (previously named Celltech Therapeutics, Ltd). P Rutgeerts has received consultancy fees from AbbVie, Bristol-Myers Squibb, Centocor, Merck, Millennium Pharmaceuticals Inc. (now Takeda) and UCB Pharma, and speaker fees and research support from AbbVie, Centocor, Merck and UCB Pharma. WJ Sandborn reports having received consulting fees from AbbVie, ActoGeniX NV, AGI Therapeutics, Inc., Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Inc., Atlantic Healthcare Limited, Aptalis, BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, Chemo-Centryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research Inc, Elan Pharmaceuticals, EnGene, Inc., Eli Lilly, Enteromedics, Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion Therapeutics, Inc., Funxional Therapeutics Limited, Genzyme Corporation, Genentech, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, Janssen, KaloBios Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals, Merck Research Laboratories, MerckSerono, Merck & Co., Millennium, Nisshin Kyorin Pharmaceuticals Co., Ltd., Novo Nordisk A/S, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, Inc., PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis Technologies, Inc., Receptos, Relypsa, Inc., Salient Pharmaceuticals, Salix Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, Sigmoid Pharma Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S.L.A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Limited (VBL), Warner Chilcott UK Limited. He has received lecture fees from AbbVie, Bristol-Myers Squibb, and Janssen. He has received research support from AbbVie, Bristol-Myers Squibb, Genentech, GlaxoSmith-Kline, Janssen, Millennium, Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals, and UCB Pharma. D Wolf reports having received consulting fees from AbbVie, Elan Pharmaceuticals, Genentech, Given Imaging, Janssen, Prometheus Laboratories, Salix Pharmaceuticals, UCB Pharma, and Warner Chilcott. He has received lectures fees from AbbVie, Janssen, Prometheus Laboratories, Santarus, Salix Pharmaceutical, Shire Pharmaceutical, and UCB Pharma. He has received research support from AbbVie, Elan Pharmaceuticals, Given Imaging, GlaxoSmithKline, Genentech, Janssen, Millennium Pharmaceutical, Pfizer, Prometheus Laboratories, Receptos, Shire Pharmaceutical, Tsumura, and UCB Pharma. W Reinisch reports having served as a speaker, a consultant and/or an advisory board member for AbbVie, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan, Ferring, Genentech, Grünenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, Austria and 4SC. G Van Assche reports having served as consultant for AbbVie, Biogen, BMS, MSD, Janssen Biologicals, Novartis; received speakers fees from AbbVie, Ferring, MSD, Janssen, UCB Pharma, Shire and financial support for research from AbbVie, Janssen Biologicals, MSD, Pfizer. S Eichner, Q Zhou, J Petersson, AM Robinson, RB Thakkar: AbbVie employees, may own AbbVie stock and/or options. This research was supported by an industry grant from AbbVie Inc.Table 1: Week 52 Efficacy in Patients Randomized to ADA Who Completed the Study on OL EOW or EW ADA Dosing