Volume 18, Issue 11 pp. 2026-2033
Original Article

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

Lior Katz MD

Lior Katz MD

Gastroenterology Department, Sheba Medical Center, Tel Hashomer, Tel-Aviv University, Israel

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Javier P. Gisbert MD, PhD

Javier P. Gisbert MD, PhD

Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

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Beth Manoogian MD

Beth Manoogian MD

University of Michigan Medical Center, Ann Arbor, USA

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Kirk Lin MD

Kirk Lin MD

Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, USA

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Casper Steenholdt MD

Casper Steenholdt MD

Department of Medical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark

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Gerassimos J. Mantzaris MD, PhD

Gerassimos J. Mantzaris MD, PhD

1st Department of Gastroenterology, Evangelismos Hospital, Athens, Greece

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Ashish Atreja MD, MPH

Ashish Atreja MD, MPH

Center for Inflammatory Bowel Disease at Cleveland Clinic, Digestive Diseases Institute in Cleveland, Ohio, USA

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Yulia Ron MD

Yulia Ron MD

Division of Gastroenterology, Tel-Aviv Medical Center, Israel

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Arun Swaminath MD

Arun Swaminath MD

Division of Gastroenterology, Columbia university Presbyterian hospital, New-York, New-York, USA

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Somal Shah MD

Somal Shah MD

University of Miami Miller School of Medicine, Miami, Florida, USA

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Ailsa Hart PhD, MRCP

Ailsa Hart PhD, MRCP

St. Marks Hospital, London, United Kingdom

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Peter Laszlo Lakatos MD, PhD

Peter Laszlo Lakatos MD, PhD

1st Department of Medicine, Semmelweis University, Budapest, Hungary

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Pierre Ellul MD

Pierre Ellul MD

Gastroenterology Department, Mater Dei Hospital, Msida, Malta

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Eran Israeli MD

Eran Israeli MD

Gastroenterology Department, Hadassah Medical Center, Jerusalem, Israel

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Mads Naundrup Svendsen MD

Mads Naundrup Svendsen MD

Medicinsk afdeling Vejle, Sygehus Hospital, Denmark

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C. Janneke van der Woude MD, PhD

C. Janneke van der Woude MD, PhD

Erasmus Medical Center, Rotterdam The Netherlands

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Konstantinos H. Katsanos MD, PhD

Konstantinos H. Katsanos MD, PhD

Hepato-Gastroenterology Unit, 1st Department of Internal Medicine, Medical School of Ioannina, Ionnina, Greece

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Laura Yun MD

Laura Yun MD

Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Epameinondas V. Tsianos MD, PhD

Epameinondas V. Tsianos MD, PhD

Hepato-Gastroenterology Unit, 1st Department of Internal Medicine, Medical School of Ioannina, Ionnina, Greece

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Torben Nathan MD

Torben Nathan MD

Medicinsk afdeling Vejle, Sygehus Hospital, Denmark

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Maria Abreu MD

Maria Abreu MD

University of Miami Miller School of Medicine, Miami, Florida, USA

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Iris Dotan MD

Iris Dotan MD

Division of Gastroenterology, Tel-Aviv Medical Center, Israel

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Bret Lashner MD, MPH

Bret Lashner MD, MPH

Center for Inflammatory Bowel Disease at Cleveland Clinic, Digestive Diseases Institute in Cleveland, Ohio, USA

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Jorn Brynskov′ MD

Jorn Brynskov′ MD

Department of Medical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark

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Jonathan P. Terdiman MD

Jonathan P. Terdiman MD

Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, USA

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Peter D.R Higgins MD, PhD

Peter D.R Higgins MD, PhD

University of Michigan Medical Center, Ann Arbor, USA

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Maria Chaparro MD, PhD

Maria Chaparro MD, PhD

Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

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Shomron Ben-Horin MD

Corresponding Author

Shomron Ben-Horin MD

Gastroenterology Department, Sheba Medical Center, Tel Hashomer, Tel-Aviv University, Israel

Gastroenterology Department, Sheba Medical Center, Tel Hashomer 52621, IsraelSearch for more papers by this author
First published: 31 January 2012
Citations: 16

Supported in part by the ‘Talpiot’ Medical Leadership program of Sheba Medical Center (to S.B.H.).

Spanish data were provided by the Spanish collaborative group ENICMAD

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;)

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