Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response

Lior Katz, Javier P. Gisbert, Beth Manoogian, Kirk Lin, Casper Steenholdt, Gerassimos J. Mantzaris, Ashish Atreja, Yulia Ron, Arun Swaminath, Somal Shah, Ailsa Hart, Peter Laszlo Lakatos, Pierre Ellul, Eran Israeli, Mads Naundrup Svendsen, C. Janneke Van Der Woude, Konstantinos H. Katsanos, Laura Hekyung Yun, Epameinondas V. Tsianos, Torben Nathan & 8 others Maria Abreu, Iris Dotan, Bret Lashner, Jorn Brynskov', Jonathan P. Terdiman, Peter D.R. Higgins, Maria Chaparro, Shomron Ben-Horin

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Background: Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling. Methods: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks). Results: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose-escalation was experienced by 86/112 (77%) patients in the dose-doubling group compared with 37/56 patients (66%) in the interval-halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose-doubling group compared with 39% in the interval-halving group (OR 1.5, 95% CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP). Conclusions: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy. (Inflamm Bowel Dis 2012;)

Original languageEnglish (US)
Pages (from-to)2026-2033
Number of pages8
JournalInflammatory bowel diseases
Volume18
Issue number11
DOIs
StatePublished - Nov 1 2012

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Crohn Disease
Odds Ratio
Infliximab
Confidence Intervals
Israel
C-Reactive Protein
Multicenter Studies
Multivariate Analysis
Retrospective Studies
Costs and Cost Analysis

Keywords

  • Crohn's disease
  • inflammatory bowel disease
  • infliximab

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Katz, L., Gisbert, J. P., Manoogian, B., Lin, K., Steenholdt, C., Mantzaris, G. J., ... Ben-Horin, S. (2012). Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response. Inflammatory bowel diseases, 18(11), 2026-2033. https://doi.org/10.1002/ibd.22902
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 Hekyung ; 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. / Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response. In: Inflammatory bowel diseases. 2012 ; Vol. 18, No. 11. pp. 2026-2033.
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abstract = "Background: Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling. Methods: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks). Results: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose-escalation was experienced by 86/112 (77{\%}) patients in the dose-doubling group compared with 37/56 patients (66{\%}) in the interval-halving group (odds ratio [OR] 1.7, 95{\%} confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50{\%} of patients in the dose-doubling group compared with 39{\%} in the interval-halving group (OR 1.5, 95{\%} CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP). Conclusions: Dose intensification leads to a sustained regained response in 47{\%} of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy. (Inflamm Bowel Dis 2012;)",
keywords = "Crohn's disease, inflammatory bowel disease, infliximab",
author = "Lior Katz and Gisbert, {Javier P.} and Beth Manoogian and Kirk Lin and Casper Steenholdt and Mantzaris, {Gerassimos J.} and Ashish Atreja and Yulia Ron and Arun Swaminath and Somal Shah and Ailsa Hart and Lakatos, {Peter Laszlo} and Pierre Ellul and Eran Israeli and Svendsen, {Mads Naundrup} and {Van Der Woude}, {C. Janneke} and Katsanos, {Konstantinos H.} and Yun, {Laura Hekyung} and Tsianos, {Epameinondas V.} and Torben Nathan and Maria Abreu and Iris Dotan and Bret Lashner and Jorn Brynskov' and Terdiman, {Jonathan P.} and Higgins, {Peter D.R.} and Maria Chaparro and Shomron Ben-Horin",
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Katz, L, Gisbert, JP, Manoogian, B, Lin, K, Steenholdt, C, Mantzaris, GJ, Atreja, A, Ron, Y, Swaminath, A, Shah, S, Hart, A, Lakatos, PL, Ellul, P, Israeli, E, Svendsen, MN, Van Der Woude, CJ, Katsanos, KH, Yun, LH, Tsianos, EV, Nathan, T, Abreu, M, Dotan, I, Lashner, B, Brynskov', J, Terdiman, JP, Higgins, PDR, Chaparro, M & Ben-Horin, S 2012, 'Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response' Inflammatory bowel diseases, vol. 18, no. 11, pp. 2026-2033. https://doi.org/10.1002/ibd.22902

Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response. / 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 Hekyung; 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.

In: Inflammatory bowel diseases, Vol. 18, No. 11, 01.11.2012, p. 2026-2033.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response

AU - Katz, Lior

AU - Gisbert, Javier P.

AU - Manoogian, Beth

AU - Lin, Kirk

AU - Steenholdt, Casper

AU - Mantzaris, Gerassimos J.

AU - Atreja, Ashish

AU - Ron, Yulia

AU - Swaminath, Arun

AU - Shah, Somal

AU - Hart, Ailsa

AU - Lakatos, Peter Laszlo

AU - Ellul, Pierre

AU - Israeli, Eran

AU - Svendsen, Mads Naundrup

AU - Van Der Woude, C. Janneke

AU - Katsanos, Konstantinos H.

AU - Yun, Laura Hekyung

AU - Tsianos, Epameinondas V.

AU - Nathan, Torben

AU - Abreu, Maria

AU - Dotan, Iris

AU - Lashner, Bret

AU - Brynskov', Jorn

AU - Terdiman, Jonathan P.

AU - Higgins, Peter D.R.

AU - Chaparro, Maria

AU - Ben-Horin, Shomron

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Background: Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling. Methods: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks). Results: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose-escalation was experienced by 86/112 (77%) patients in the dose-doubling group compared with 37/56 patients (66%) in the interval-halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose-doubling group compared with 39% in the interval-halving group (OR 1.5, 95% CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP). Conclusions: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy. (Inflamm Bowel Dis 2012;)

AB - Background: Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling. Methods: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks). Results: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose-escalation was experienced by 86/112 (77%) patients in the dose-doubling group compared with 37/56 patients (66%) in the interval-halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose-doubling group compared with 39% in the interval-halving group (OR 1.5, 95% CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP). Conclusions: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy. (Inflamm Bowel Dis 2012;)

KW - Crohn's disease

KW - inflammatory bowel disease

KW - infliximab

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DO - 10.1002/ibd.22902

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