Early remission status predicts long-term outcomes in patients with Crohn’s disease treated with certolizumab pegol

Abstract

Background: In Crohn’s disease (CD), rapid response to anti–tumor necrosis factor therapy improves short- and medium-term outcomes, but the relationship between early remission (ER) and long-term remission is unclear.

Aims: This exploratory analysis of PRECiSE 3 (NCT00160524) assessed whether ER after initiation of certolizumab pegol predicted long-term remission.

Methods: Patients enrolled in PRECiSE 3 had completed PRECiSE 1 or 2, two randomized placebo-controlled studies for moderate to severe CD, and received open-label certolizumab pegol 400 mg every 4 weeks for a total treatment duration of ≤7.5 years. Time to loss of remission between patients with and without ER (Harvey–Bradshaw Index ≤4 at or before Week 6 of PRECiSE 1 or 2) was compared by log-rank test of Kaplan–Meier estimates.

Results: At baseline, patients with (n = 242) and without (n = 148) ER had mean (standard deviation [SD]) durations of CD of 6.8 (6.6) and 7.4 (7.8) years, mean (SD) CD Activity Index scores of 280.3 (53.4) and 311.1 (55.5), with 45.5% and 41.9% of patients having ileocolonic CD, and median C-reactive protein concentrations of 8.0 and 5.0 mg/L, respectively. Median certolizumab pegol plasma concentrations during the first 6 weeks of therapy were similar in both groups. Mean time to loss of remission was significantly longer in patients with versus without ER (2.77 vs. 1.14 years, p < 0.0001).

Conclusions: In certolizumab pegol–treated patients with CD, ER appears to be an important predictor of long-term clinical remission. Prospective trials are needed to determine whether ER improves other long-term outcomes.

Keywords:

• Anti-TNFα therapy
• Certolizumab pegol
• Crohn’s disease
• Early remission
• PRECiSE 3

Transparency

Declaration of funding

Writing and editorial assistance for the studies and analyses presented herein were funded by UCB Pharma.

Declaration of financial/other relationships

G.Y.M. has disclosed that he has served as a speaker, consultant, or advisory board member for AbbVie, Genentech, Given Imaging, Janssen Orthobiotech, Luitpold/American Regent, Takeda, and UCB Pharma, and has received research funding from Pfizer and Prometheus Labs. D.McG. has disclosed that he has served as a consultant or advisory board member for Ferring, Genentech, Janssen, Merck, Novo Nordisk, and UCB Pharma. S.S. has disclosed that he has served on advisory boards for AbbVie, MSD, Pfizer, and UCB Pharma, and has received lecture fees for AbbVie and MSD. G.K., M.S., and J.C. have disclosed that they are employees of UCB Pharma. W.J.S. has disclosed that he has served as a speaker, consultant, or advisory board member for Abbott, ActoGeniX NV, AGI, Alba, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Atlantic Healthcare, Axcan (now Aptalis), BioBalance, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celek, Cellerix SL, Cerimon, ChemoCentryx, CoMentis, Cosmo, Coronado Biosciences, Cytokine PharmaSciences, Eagle Pharmaceuticals, Eisai, Elan, enGene, Eli Lilly, EnteroMedics, Exagen Diagnostics, Ferring, Flexion, Funxional Therapeutics, Genzyme, Genentech (Roche), Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, Janssen, KaloBios, Lexicon Pharmaceuticals, Lycera, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millennium (Takeda), Nisshin Kyorin, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen, PDL BioPharma, Pfizer, Procter & Gamble, Prometheus, ProtAb, PurGenesis, Receptos, Relypsa, Salient, Salix, Santarus, Schering-Plough, Shire, Sigmoid Pharma, Sirtris, S.L.A. Pharma, Targacept, Teva, Therakos, Tillotts Pharma, TxCell SA, UCB Pharma, Viamet, Vascular Biogenics, Warner Chilcott, and Wyeth (Pfizer); he received speakers’ fees from Abbott, Bristol-Myers Squibb, and Janssen; and research support from Abbott, Bristol-Myers Squibb, Genentech (Roche), GlaxoSmithKline, Janssen, Millennium (Takeda), Novartis, Pfizer, Procter & Gamble, Shire, and UCB Pharma.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

Writing assistance was provided by Roland Tacke PhD and Patricia McChesney PhD CMPP of Evidence Scientific Solutions and was funded by UCB Pharma.

We thank the investigators as well as the patients and their caregivers who participated in the PRECiSE 1, 2, and 3 studies.

Previous presentation: Data from this post-hoc analysis of data from previously published studies (ClinicalTrials.gov NCT00152490, NCT00152425, NCT00552058) was presented at Digestive Disease Week, 16–19 May 2015, Washington, DC, USA.