Disease Activity as a Predictor of Long-Term Outcomes of Treatment With Certolizumab Pegol for Active Crohn’s Disease: An Analysis of the PRECiSE 3 Study (2014)

Introduction: The aim of this analysis was to explore the impact of baseline disease activity on long-term outcomes in patients with moderate-severe Crohn’s disease (CD) who were treated with certolizumab pegol (CZP) over 7 years in the PRECiSE 3 (P3) study, an open-label extension in patients who had completed a 26 week blinded study of CZP (PRECiSE 1 or 2). A multivariate analysis has identified the Harvey-Bradshaw index (HBI) as an important factor associated with maintenance of remission. We report the univariate results of this factor. Methods: In P3, patients received CZP 400 mg every 4 weeks from week 2 to week 364. For this exploratory analysis, patients were categorized by their disease activity at baseline (week 0) of the qualifying study, as measured by the HBI (HBI <8 vs. ≥8). Remission was defined as HBI ≤4. Results: Of the 592 patients who were evaluated, 447 (75.5%) had a baseline HBI ≥8. At screening, the mean (SD) age was 38.6 (11.8) years for patients with HBI ≥8 vs. 36.4 (12.0) years for patients with HBI <8; the percentage of women was 53.0% vs. 47.6%, and the mean (SD) body mass index was 24.5 (5.6) vs. 23.2 (5.1) kg/m2. Patients with HBI ≥8 had a longer disease duration at baseline (mean [SD] 7.5 [7.2] vs. 6.6 [7.5] years) and a higher percentage of ileocolonic disease than patients with HBI <8 (48.1% vs. 40.0). A significantly higher percentage with HBI ≥8 had a history of resections (33.8% vs. 20.7%; p=0.0030). Differences in other demographic variables were not clinically meaningful. Patients with HBI ≥8 had a more rapid loss of remission than patients with HBI <8 (Figure 1). The mean (SE) duration of time to loss of remission for patients with HBI ≥8 was 2.06 (0.14) vs. 2.45 (0.22) years for patients with HBI <8 (p=0.0208).Figure 1: Time to loss of remission by baseline Harvey-Bradshaw Index categories starting from qualifying studies PRECiSE 1 and PRECiSE 2.Conclusion: Baseline HBI was an important, independent univariate component affecting long-term outcomes in patients with CD who were treated with CZP over 7 years. Clinicaltrials.gov identifier: NCT00160524. Censored patients are those who discontinued from the study for reasons other than loss of remission or lack of efficacy. Disclosure - Jennifer M Choi - Speakers Bureau Member: AbbVie, Janssen, UCB and Consulting Fee/Advisory Board: AbbVie, Genentech, Janssen, UCB. Bincy Abraham - Speakers Bureau Member: Janssen, Takeda, Abbvie, UCB, Salix, Prometheus, Consulting Fee/Advisory Board: UCB, Janssen, Abbvie, Prometheus. Douglas C. Wolf - Advisory Committees or Review Panels: Salix Pharmaceuticals; Consulting: AbbVie, UCB Pharma; Grant/Research Support: AbbVie, Janssen Biotech Inc, Janssen Biotech Inc, UCB Pharma, Shire, Prometheus Laboratories, Prometheus Laboratories, Warner Chilcott, Millennium Research Group, GIVEN Imaging, GIVEN Imaging, Elan; Speaking and Teaching: AbbVie, Janssen Biotech Inc, UCB Pharma, Santarus, Prometheus Laboratories. Remo Panaccione - Advisory Committees or Review Panels: Abbott, Axcan Pharma Inc., Centocor, Inc., Chemocentryx, PDL BioPharma, Inc., Novartis Pharmaceuticals, Genentech Inc., Elan Pharmaceuticals, Inc.; Consulting: Abbott, Biogen/IDEC, Axcan Pharma Inc., Bristol-Myers Squibb, Chemocentryx, Ferring Pharmaceuticals Inc, Genentech Inc., Elan Pharmaceuticals, Inc., UCB, Inc.; Grant/Research Support: Abbott, Osiris Therapeutics, Inc., UCB, Inc.; Independent Contractor: Lippincott Williams & Wilkins; Speaking and Teaching: Abbott, Centocor, Inc., Medscape, Elan Pharmaceuticals, Inc. Jean-Frederic Colombel - Consulting Fee/Advisory Board: Abbvie, ABScience, Amgen, Bristol Meyers Squibb, Celltrion, Danone, Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen, Immune Pharmaceuticals, Merck & Co., Millenium Pharmaceuticals Inc., Nutrition Science Partners Ltd., Pfizer Inc. Prometheus Laboratories, Protagonsit, Receptos, Sanofi, Schering Plough Corporation, Second Genome, Takeda, Teva Pharmaceuticals, UCB Pharma, Vertex, Dr. August Wolff GmbH & Co. Company Ownership (incl stock options, excluding mutual funds): Intestinal Biotech Development. Gordana Kosutic, Marshall Spearman, and Jason Coarse 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, 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 KlineGlaxoSmith-Kline, 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.