Achievement of Early Deep Remission Is Associated with Lower Rates of Weekly Dosing for Adalimumab-Treated Patients with Crohnʼs Disease: Data from EXTEND

Abstract

Purpose: To explore the relationship between early deep remission and rates of dosage adjustment for patients with Crohn's disease (CD). Methods: EXTEND was a study of the effects of adalimumab on mucosal healing in patients with moderate to severe ileocolonic CD (Crohn's Disease Activity Index [CDAI] 220-450). Patients received open-label adalimumab 160-/80-mg induction therapy at Weeks 0/2 and were randomized at Week 4 to maintenance therapy with adalimumab 40 mg every other week (eow) or placebo through Week 52. From Week 8, patients with flares or nonresponse could receive open-label adalimumab 40 mg eow. The maintenance regimen could be adjusted to weekly open-label adalimumab for continued flares/non-response. Endoscopic assessments of mucosal disease activity were performed at baseline, Week 12 (or unscheduled visits Weeks 8-12 prior to switch to open-label), time of switch to open-label adalimumab (if after Week 12), and Week 52 (or early termination). Early deep remission was defined as mucosal healing (visually determined) plus clinical remission (CDAI <150) at Week 12. Rates of moving to open-label eow and weekly therapy through Week 52 were compared between patients randomized to blinded adalimumab maintenance therapy who achieved Week-12 deep remission and those who did not. Results: Sixty-four patients were randomized to adalimumab maintenance therapy at Week 4. Adalimumab-treated patients who achieved deep remission by Week 12 had significantly lower rates of dosage adjustment compared with patients not achieving early deep remission (table). No patients achieving early deep remission moved to weekly therapy. Conclusion: Deep remission, defined as complete mucosal healing plus clinical remission, may be an important treatment goal in CD. Patients in EXTEND who achieved deep remission by Week 12 were less likely than those who did not achieve deep remission to move to open-label eow dosing and subsequently receive weekly therapy. Disclosure: WJ Sandborn: Consultant and/or Advisory Board: Abbott (fees paid to employer, Mayo Clinic), ActoGeniX, AGI Therapeutics, Alba Therapeutics, Albireo, AM-Pharma, Amgen, Ardea Biosciences, Aspreva, Astellas, Athersys, Atlantic Healthcare, Axcan, BioBalance, Bristol-Myers Squibb, Celegene, Celek, Cellerix, Centocor Ortho Biotech (fees paid to employer, Mayo Clinic), Cerimon, Chemocentryx, CombinatoRx, CoMentis, Cosmo Technologies, Cytokine Pharmasciences, Eagle, Eisai Medical Research, Elan, Enteromedics, Enzo Therapeutics, Ferring, Flexion Therapeutics, Funxional Therapeutics, Genentech, Genzyme, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Hutchison Medipharma, Ironwood, KaloBios, Merck Research Laboratories, MerckSerono, Millennium Pharmaceuticals, Nisshin Kyorin, Novo Nordisk, Ocera Therapeutics, Pfizer, Procter & Gamble (fees paid to employer, Mayo Clinic), Prometheus, Purgenesis Technologies, Salient, Salix, Santarus, Schering-Plough, Shire (fees paid to employer, Mayo Clinic), Sigmoid, Sirtris, SLA (UK), Teva, Tillotts, Tioga, UCB (fees paid to employer, Mayo Clinic), VBL, Ventech, Viamet, Wyeth. Research Support: Abbott, Bristol-Myers Squibb, Celltech, Centocor Ortho Biotech, Genentech, Millennium Pharmaceuticals, Novartis, Otsuka American, PDL Biopharma, Pfizer, Procter & Gamble, Robarts Research Institute, Shire, UCB. J-F Colombel: Advisory Boards and/or Consulting: Abbott, ActoGeniX, 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. PM Mulani: 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. M Yang: Employee/Stock: Abbott. J Chao: Employee/Stock: Abbott.Table: [1208] Rates of adalimumab dosage adjustment with and without early deep remission