Disease Location as a Risk Determinant for Maintenance of Remission in Crohn’s Disease Patients Treated With Certolizumab Pegol: Results of Analyses From the PRECiSE 3 Study (2014)

Introduction: Disease location affects the response of patients with Crohn’s disease (CD) to treatment. Multivariate analyses of data from the PRECiSE 3 (P3) study identified disease location as a risk determinant for maintenance of remission in patients treated with certolizumab pegol (CZP) over 7 years. These univariate analyses investigated the impact of disease location on the duration of remission. Methods: In P3, patients received CZP 400 mg every 4 weeks for up to 7 years. For this analysis, patients were stratified by disease location at baseline of P1 or P2 (terminal ileum/ileocolon vs. colon only) as reported by the investigators. Log-rank tests were used to examine the differences in Kaplan-Meier estimates for duration of remission (defined as Harvey Bradshaw index ≤4) between the 2 groups. Results: Of the 571 patients (52% female), 417 (73%) had disease in the terminal ileum/ileocolon with these patients having a longer duration of CD vs. patients with colon only disease (mean [SD] 7.9 [7.5] years vs. 5.8 [6.6] years), and a higher percentage of previous resections (39.6% vs. 5.2%). A more rapid loss of remission was observed in patients whose disease was located in the terminal ileum/ileocolon vs. colon only disease, with a mean (SE) time to loss of remission of 2.01 (0.14) years vs. 2.19 (0.19) years (p=0.01) (Figure 1).Figure 1: Time to loss of remission by disease location at baseline of the qualifying studies PRECiSE 1 and PRECiSE 2.Conclusion: Disease location may be an important predictor of a more durable maintenance of remission with CZP in CD patients. The patients with terminal ileum/ileocolonic location had a more rapid loss of remission over a 7-year period than those with isolated colonic disease. This relationship needs to be confirmed through secondary analysis of other anti-TNF maintenance cohorts. Clinicaltrials.gov identifier: NCT00160524. Disclosure - Stefan Schreiber - Consulting Fee/Advisory Board: Abbvie, MSD, Jansen, Takeda, Hospira, UCB, Federal Funding: German Government, EU Funding, NIH. Charles Randall - grant support, consulting fees, and am a member of the speakers bureaus of UCB, Janssen, Takeda, Forest, Furiex, Ironwood, BMS, Amgen, Salix, Prometheus, Luitpold, Cottonwood, and Menarini. Marla Dubinsky: Consultant: Jannsen, Bristol Myers Squibb, UCB, Abbott, Shire, Prometheus, Takeda. Gordana Kosutic, Bosny Pierre-Louis, and Marshall Spearman are employees of UCB Pharma and have stocks and stock options. William Sandborn - Consulting fees: 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, 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 (now Roche), Gilead Sciences, Given Imaging, Glaxo Smith KlineGlaxo-SmithKline, 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.