Serum Albumin as a Predictor of Long-Term Response and Remission With Certolizumab Pegol for Crohn’s Disease: Results From 7-Year Data From the PRECiSE 3 Study (2014)

Introduction: Exploratory analyses suggest that low serum albumin concentration (SAC) may be associated with more rapid clearance of anti-tumor necrosis factor (anti-TNF) agents and poorer outcomes. The current analyses explore associations between SAC at screening in double-blind controlled studies for Crohn’s disease (CD) treatment with certolizumab pegol (CZP), and long-term efficacy in an extension study, PRECiSE 3 (P3). Methods: P3 was a phase 3, open-label study of CZP 400 mg every 4 weeks up to 7 years in patients with moderate-to-severe CD who completed the initial studies. The patient data were grouped by low SAC (<35 g/L) or normal SAC (≥35 g/L) at screening. Loss of response/remission (Harvey-Bradshaw index [HBI] was defined: response = change ≥3, remission = ≤4). Univariate analysis was based on Kaplan-Meier curves; log-rank p value was used to compare survival distribution. Results: Of the 594 patients evaluated, 42 (7%) had low SAC. Mean (SD) age was 38 (14) years (low SAC) and 38 (12) years (normal SAC). Disease duration and location of CD were similar between groups. Higher percentages of patients with low SAC had stricturing/penetrating disease (21%/24%) vs. normal SAC (12%/19%). Mean (standard error) time to loss of response was 1.71 (0.40) years (low SAC) vs. 3.18 (0.14) years (normal SAC, p=0.0017, Figure 1); time to loss of remission was 0.83 (0.19) years vs. 2.26 (0.13) years, respectively (p=0.0073).Figure 1: PRECiSE 3 - Time to loss of response (change HBI (3 from baseline) starting from PRECiSE 1 and PRECiSE 2. Analysis set: intention to treat.Conclusion: Low SAC may reflect more severe CD and measuring it may be clinically useful for predicting response to therapy and the possible need for advanced treatments. Clinicaltrials.gov identifier: NCT00160524. Disclosure - William Sandborn: Abbott Laboratories, ActoGeniX NV, AGI Therapeutics, Inc., Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas Pharma, Athersys, Inc., Atlantic Healthcare Limited, Axcan Pharma (now Aptalis), BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol Meyers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, 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 (now Roche), Gilead Sciences, Given Imaging, Glaxo Smith KlineGlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals (previously Microbia Inc.), Janssen (previously Centocor), KaloBios Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals (previously Alaven Pharmaceuticals), Merck Research Laboratories, MerckSeronoMerck Serono, Millennium Pharmaceuticals (subsequently merged with Takeda), 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, Schering Plough Corporation (acquired by Merck), Shire Pharmaceuticals, Sigmoid Pharma Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S.L.A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG (acquired by Zeria Pharmaceutical Co., Ltd), TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics LimitedLtd. (VBL), Warner Chilcott UK Limited, and Wyeth (now Pfizer). Speakers fees: Abbott Laboratories, Bristol Meyers Squibb, and Janssen (previously Centocor). Financial support for research: Abbott Laboratories, Bristol Meyers Squibb, Genentech, Glaxo Smith Kline (now Roche), GlaxoSmithKline, Janssen (previously Centocor), Millennium Pharmaceuticals (now Takeda), Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals, and UCB Pharma. CR: Ironwood Pharmaceuticals, Forest Labs, Santarus Pharmaceuticals, Salix Pharmaceuticals, Boston Scientific, Takeda, Prometheus, UCB, Janssen, and Santarus. Finlay A. Macrae - Advisory Committees or Review Panels: Janssen-Cilag, Janssen-Cilag, CSIRO, SLA Pharma; Consulting: Australian Commonwealth Scientific Industrial Rese; Grant/Research Support: Abbott, UCB, Inc., Centocor, Inc., Millenium, Given Imaging, Olympus America, Inc., Optiscan, Schering Plough, Hicks Foundation, Cancer Australia, Aust National Health and Medical Research Council, Victorian Government, Glutagen Pty Ltd, Coeliac Research Fund, Australian Wine Research Institute, Bristol Myer Squibb. Ian C. Lawrance - Advisory Committees or Review Panels: Abbott Australasia, GlaxoSmithKline, Merck & Co, Shire, Pharmatel Fresenius Kabi, Takeda Pharmaceuticals International Co. David Sen and Sarah Abbas: employees of UCB Pharma and have stocks and stock options. Kevin Douglas: employee of UCB Pharma at the time of the study.Gary Lichtenstein: Consultant: Abbott Corporation / Abbvie, Alaven, Elan, Hospira, Millenium Pharmaceuticals, Ono Pharmaceuticals, Pfizer Pharmaceuticals, Takeda, Consultant, Research: Prometheus Laboratories, Inc., Salix Pharmaceuticals, Santarus, Shire Pharmaceuticals, UCB, Janssen Orthobiotech, Ferring, Research: Bristol-Myers Squibb, Honorarium (CME Program): Ironwood, Consulting, Honorarium (CME Program): Luitpold / American Regent, Consultant, Research, Grant: Warner Chilcotte.