Achievement of Early Deep Remission Predicts Better Long-Term Outcomes for Adalimumab-Treated Patients with Crohnʼs Disease: Data from EXTEND (2010)

Purpose: To explore the impact of early deep remission on long-term outcomes in the 52-week EXTEND trial. Methods: Patients in EXTEND, a study of mucosal healing in patients with moderate to severe ileocolonic CD (CDAI 220-450), received open-label adalimumab 160-/80-mg induction therapy at Weeks 0/2 and were randomized at Week 4 to maintenance therapy with adalimumab (ADA) 40 mg every other week (eow) or placebo through Week 52. From Week 8, patients with flares/nonresponse could receive open-label (OL) ADA 40 mg eow (weekly if flares/nonresponse continued). Endoscopic assessment was performed at baseline, Week 12 (or unscheduled visits at Weeks 8-12 prior to switch to OL or dropout), time of switch to OL (if after Week 12), and Week 52 (or early termination). Early deep remission was defined as observed mucosal healing+clinical remission (CDAI <150) at Week 12. Relationships of early deep remission with Inflammatory Bowel Disease Questionnaire (IBDQ) remission status (IBDQ ≥170), Short-Form 36 Health Survey (SF-36) normal status (Physical Component Summary [PCS]/Mental Component Summary [MCS] ≥50), and Work Productivity and Activity Impairment Questionnaire (WPAI) improvements at Week 52 and hospitalization from Week 12 through Week 52 were assessed. Data were analyzed using multiple linear regressions and logistic regressions, with control for baseline QOL/WPAI scores. Results: ADA-treated patients achieving early deep remission tended to have fewer hospitalizations, better Week-52 QOL, and less productivity impairment compared with patients not achieving deep remission (table). Patients with early deep remission were ˜5 times more likely to achieve both IBDQ remission and a normal SF-36 PCS score (both p<0.05) at Week 52. No patients achieving early deep remission were hospitalized. There were 3 CD-related surgeries in the non-deep remission group and 0 in the deep remission group. Conclusion: Achievement of early deep remission predicted better long-term outcomes in ADA-treated patients with moderate to severe ileocolonic CD. Disclosure: J-F Colombel: Advisory Boards and/or Consulting: Abbott, Acto-GeniX, Albireo Pharma, Astra Zeneca, Bayer Schering Pharma, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix SL, Centocor, Chemocentryx Inc, Cosmo Technologies Ltd, Danone France, Elan Pharmaceuticals Inc, Genentech, Giuliani SPA, Given Imaging, GlaxoSmithKline, Merck and Co Inc, Millenium Pharmaceuticals Inc, NeoVacs SA, Ocerra Therapeutics Inc (previously named Renovia Inc), Otsuka American Pharmaceuticals Inc, PDL Biopharma (previously named Protein Design Labs), Pfizer Inc, Ribo Vacs Biotech, Schering-Plough Corporation, Shire Pharmaceuticals, Synta Pharmaceutical Corporation, Teva Pharmaceuticals and Petah Tikva, Therakos, UCB Pharma (previously named Celltech Therapeutics Ltd) and Wyeth Pharmaceuticals. Grant Support: Astra-Zeneca, Danisco, Danone, Dysphar, Ferring, Giuliani SPA, Lesaffre, Mapi Naxis, Ocerra Therapeutics Inc (previously named Renovia Inc), Roquette, Schering-Plough Corporation, UCB Pharma. Lecture Fees from speaking at continuing medical education events indirectly sponsored by a commercial sponsor: Abbott, Astra Zeneca, Centocor, Elan Pharmaceuticals Inc, Falk Pharma, Ferring, Given Imaging, Otsuka American Pharmaceuticals Inc, PDL Biopharma, Schering-Plough Corporation, Shire Pharmaceuticals, UCB Pharma. Stock: Intestinal Biotech Development. P Rutgeerts: Advisor: Elan Pharmaceuticals; Ferring Pharmaceuticals; Procter and Gamble; Schering-Plough; UCB. Consultant: Abbott; Astra Zeneca; Bristol-Myers Squibb; Centocor; Elan Pharmaceuticals; Ferring Pharmaceuticals; GlaxoSmithKline; Procter and Gamble; Schering-Plough; Shire; UCB. Grant/Research Support: Abbott; Bristol-Myers Squibb; Centocor; Elan Pharmaceuticals; Ferring Pharmaceuticals; Millenium Pharmaceuticals; Procter and Gamble; Schering-Plough. Speaker's Fees: Abbott; Astra Zeneca; Axcan Pharma; Byk Solvay; Centocor; Elan Pharmaceuticals; Jansen; Procter and Gamble; Prometheus; Schering-Plough; Shire. WJ Sandborn: Financial Support for Research: Abbott Laboratories, Bristol Meyers Squibb, CentocorOrthoBiotech, Genentech, Millennium Pharmaceuticals, Novartis, Pfizer, Shire Pharmaceuticals, UCB Pharma, Warner Chilcott (previously Procter & Gamble). Lecture Fees: None. Consultancy: ActoGenix, Abbott Laboratories (fees paid to Mayo), AGI Therapeutics, Albireo, Alfa Wassermann, AM-Pharma, Amgen, Anaphore, Astellas Pharma, Athersys, Atlantic Healthcare Limited, Axcan Pharma, BioBalance Corporation, Celegene, Bristol Meyers Squibb (fees paid to Mayo), Celek Pharmaceuticals, Cellerix, CentocorOrthoBiotech (fees paid to Mayo), Chemocentryix, CoMentis, Cosmo Technologies, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research, Elan Pharmaceuticals (fees paid to Mayo), Eli Lilly, Enteromedics, Ferring Pharmaceuticals, Flexion Therapeutics, Funxional Therapeutics Limited, Genentech (fees paid to Mayo), Given Imaging, GlaxoSmithKline, KaloBios Pharmaceuticals, Merck Research Laboratories, Merck Serono, Novo Nordisk, Pfizer (fees paid to Mayo), Procter & Gamble (fees paid to Mayo), Purgenesis Technologies, Regeneron Pharmaceuticals, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering Plough Corporation, Shire Pharmaceuticals (fees paid to Mayo), Sigmoid Pharma, Sitrtis Pharmaceuticals, SLA Pharma, Takeda (fees paid to Mayo), Tillotts Pharma, UCB Pharma (fees paid to Mayo), Vascular Biogenics, Viamet Pharmaceuticals, Wyeth. Shareholder: None. Directorships: None. Other: None. M Yang: Employee/Stock: Abbott. KG Lomax: Employee/Stock: Abbott. PF Pollack: Employee/Stock: Abbott. R Thakkar: Employee/Stock: Abbott. A Camez: Employee/Stock: Abbott. N Chen: Employee/Stock: Abbott. J Chao: Employee/Stock: Abbott. PM Mulani: Employee/Stock: Abbott.Table: [1190]