Time-In-Remission Analysis of Adalimumab vs. Placebo for the Treatment of Ulcerative Colitis

Abstract

Purpose: Previous research has reported clinical remission and response rates for the ULTRA 2 trial, showing the benefits of adalimumab (ADA) therapy in patients with moderate to severe ulcerative colitis (UC). However, the length of clinical remission and response, which is directly related to patients' daily quality of life, has not been reported. Using data from the ULTRA 2 trial, we compared the number of days in clinical remission, clinical response, Inflammatory Bowel Disease Questionnaire (IBDQ) remission, and serious adverse event (SAE)-adjusted days in clinical remission in ADA- and placebo (PBO)-treated patients in a post-hoc analysis. Methods: The study population included 494 who had previously failed or were currently failing steroids and/or immunosuppressants (including 40% of patients who had prior anti-tumor necrosis factor experience): 248 in the ADA group (160 mg/80 mg at Weeks 0/2 as induction followed by 40 mg every other week) and 246 in the PBO group. Clinical remission was defined by a Mayo (or partial Mayo) score ≤2 and no individual subscore >1. Clinical response was defined by a decrease in Mayo score ≥3 points (or partial Mayo score ≥2 points) and ≥30% from baseline, plus a decrease in rectal bleeding score ≥1 from baseline or an absolute rectal bleeding score ≤1. IBDQ remission was defined as an IBDQ score ≥170. Statistical significance between treatment groups was assessed by Student t-test for clinical remission, clinical response, and IBDQ remission. The number of SAE-adjusted days in clinical remission was calculated as the number of days in clinical remission minus the number of days with SAEs. A Wald test was used to compare SAE-adjusted days in clinical remission between the treatment groups. Results: During the double-blind period, ADA-treated patients spent significantly more days in clinical remission (61% more days), clinical response (42% more days), and IBDQ remission (32% more days) as well as significantly more SAE-adjusted days in clinical remission (68% more days) than did PBO-treated patients (Table).Table: Time in clinical remission, clinical response, and IBDQ remissionaConclusion: ADA therapy exhibited a benefit/risk profile superior to placebo for use in the treatment of moderate to severe UC. Disclosure: Gert Van Assche: Consultancy: PDL Biopharma, Sanofi-aventis, UCB. Financial support for research: Abbott, Ferring. Lecture fee(s): Janssen-Cilag, Schering-Plough. Andreas Lazar: Employee & Stockholder: Abbott Roopal B Thakkar: Employee & Stockholder: Abbott Mei Yang: Employee & Stockholder: Abbott Martha Skup: Employee & Stockholder: Abbott Parvez M Mulani: Employee & Stockholder: Abbott Jingdong Chao: Employee & Stockholder: Abbott William J Sandborn: Financial Support for Research: Abbott, Bristol-Myers Squibb, Centocor Ortho Biotech, Genentech, Millennium, Novartis, Pfizer, Shire, UCB, Warner Chilcott. Consultancy: ActoGeniX, Abbott, AGI Therapeutics, Albireo, Alfa Wassermann, AM-Pharma, Amgen, Anaphore, Astellas, Athersys, Atlantic Healthcare, Axcan, BioBalance, Celgene, Bristol-Myers Squibb, Celek, Cellerix, Centocor Ortho Biotech, ChemoCentryx, CoMentis, Cosmo Technologies, Cytokine PharmaSciences, Eagle, Eisai Medical Research, Elan, Eli Lilly, EnteroMedics, Ferring, Flexion, Funxional Therapeutics, Genentech, Given Imaging, GlaxoSmithKline, KaloBios, Merck Research Labs, Merck Serono, Novo Nordisk, Pfizer, Procter & Gamble, PurGenesis Technologies, Regeneron, Salient, Salix, Santarus, Schering-Plough, Shire, Sigmoid, Sirtris, SLA, Takeda, Tillotts, UCB, Vascular Biogenics, Viamet, Wyeth.