An Accelerated Infliximab Induction Regimen Reduces the Need for Early Colectomy in Patients With Acute Severe Ulcerative Colitis

被引:215
作者
Gibson, David J. [1 ]
Heetun, Zaid S.
Redmond, Ciaran E.
Nanda, Kavin S.
Keegan, Denise
Byrne, Kathryn
Mulcahy, Hugh E.
Cullen, Garret
Doherty, Glen A.
机构
[1] St Vincents Univ Hosp, Ctr Colorectal Dis, Dublin 4, Ireland
关键词
Ulcerative Colitis; Infliximab; Accelerated Induction; INFLAMMATORY-BOWEL-DISEASE; C-REACTIVE PROTEIN; CROHNS-DISEASE; MONOCLONAL-ANTIBODIES; CLINICAL-RESPONSE; RESCUE THERAPY; PHARMACOKINETICS; CYCLOSPORINE; CLEARANCE; REMISSION;
D O I
10.1016/j.cgh.2014.07.041
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
BACKGROUND & AIMS: Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect. METHODS: We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods. RESULTS: There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03). CONCLUSIONS: In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.
引用
收藏
页码:330 / U170
页数:7
相关论文
共 22 条
[1]
Brandse JF, 2013, FECAL LOSS INFLIXIMA
[2]
Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 1: Definitions and diagnosis [J].
Dignass, Axel ;
Eliakim, Rami ;
Magro, Fernando ;
Maaser, Christian ;
Chowers, Yehuda ;
Geboes, Karel ;
Mantzaris, Gerassimos ;
Reinisch, Walter ;
Colombel, Jean-Frederic ;
Vermeire, Severine ;
Travis, Simon ;
Lindsay, James O. ;
Van Assche, Gert .
JOURNAL OF CROHNS & COLITIS, 2012, 6 (10) :965-990
[3]
Fasanmade AA, 2010, INT J CLIN PHARM TH, V48, P297
[4]
SIGNIFICANCE OF SYSTEMIC ENDOTOXEMIA IN INFLAMMATORY BOWEL-DISEASE [J].
GARDINER, KR ;
HALLIDAY, MI ;
BARCLAY, GR ;
MILNE, L ;
BROWN, D ;
STEPHENS, S ;
MAXWELL, RJ ;
ROWLANDS, BJ .
GUT, 1995, 36 (06) :897-901
[5]
Infliximab for the treatment of ulcerative colitis: outcomes in Oxford from 2000 to 2006 [J].
Jakobovits, S. L. ;
Jewell, D. P. ;
Travis, S. P. L. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2007, 25 (09) :1055-1060
[6]
Infliximab as rescue therapy in severe to moderately severe ulcerative colitis:: A randomized, placebo-controlled study [J].
Järnerot, G ;
Hertervig, E ;
Friis-Liby, I ;
Blomquist, L ;
Karlé, P ;
Grännö, C ;
Vilien, M ;
Ström, M ;
Danielsson, Å ;
Verbaan, H ;
Hellström, PM ;
Magnuson, A ;
Curman, B .
GASTROENTEROLOGY, 2005, 128 (07) :1805-1811
[7]
KAPEL N, 1992, EUR J CLIN CHEM CLIN, V30, P197
[8]
Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response [J].
Katz, Lior ;
Gisbert, Javier P. ;
Manoogian, Beth ;
Lin, Kirk ;
Steenholdt, Casper ;
Mantzaris, Gerassimos J. ;
Atreja, Ashish ;
Ron, Yulia ;
Swaminath, Arun ;
Shah, Somal ;
Hart, Ailsa ;
Lakatos, Peter Laszlo ;
Ellul, Pierre ;
Israeli, Eran ;
Svendsen, Mads Naundrup ;
van der Woude, C. Janneke ;
Katsanos, Konstantinos H. ;
Yun, Laura ;
Tsianos, Epameinondas V. ;
Nathan, Torben ;
Abreu, Maria ;
Dotan, Iris ;
Lashner, Bret ;
Brynskov', Jorn ;
Terdiman, Jonathan P. ;
Higgins, Peter D. R. ;
Chaparro, Maria ;
Ben-Horin, Shomron .
INFLAMMATORY BOWEL DISEASES, 2012, 18 (11) :2026-2033
[9]
Kevans D, 2012, GASTROENTEROLOGY, V142, pS384
[10]
Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial [J].
Laharie, David ;
Bourreille, Arnaud ;
Branche, Julien ;
Allez, Matthieu ;
Bouhnik, Yoram ;
Filippi, Jerome ;
Zerbib, Frank ;
Savoye, Guillaume ;
Nachury, Maria ;
Moreau, Jacques ;
Delchier, Jean-Charles ;
Cosnes, Jacques ;
Ricart, Elena ;
Dewit, Olivier ;
Lopez-Sanroman, Antonio ;
Dupas, Jean-Louis ;
Carbonnel, Franck ;
Bommelaer, Gilles ;
Coffin, Benoit ;
Roblin, Xavier ;
Van Assche, Gert ;
Esteve, Maria ;
Farkkila, Martti ;
Gisbert, Javier P. ;
Marteau, Philippe ;
Nahon, Stephane ;
de Vos, Martine ;
Franchimont, Denis ;
Mary, Jean-Yves ;
Colombel, Jean-Frederic ;
Lemann, Marc .
LANCET, 2012, 380 (9857) :1909-1915