title: Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response.
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.
authors.affiliation: Gastroenterology Department, Sheba Medical Center, Tel Hashomer, Tel-Aviv University, Israel.
authors.forename: Lior
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authors.initials: JP
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authors.lastname: Lin
authors.forename: Casper
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authors.forename: Gerassimos J
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authors.forename: Yulia
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authors.lastname: Ron
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authors.forename: Somal
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authors.lastname: Shah
authors.forename: Ailsa
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authors.initials: PL
authors.lastname: Lakatos
authors.forename: Pierre
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authors.lastname: Ellul
authors.forename: Eran
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authors.lastname: Israeli
authors.forename: Mads Naundrup
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authors.lastname: Svendsen
authors.forename: C Janneke
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authors.lastname: van der Woude
authors.forename: Konstantinos H
authors.initials: KH
authors.lastname: Katsanos
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authors.lastname: Yun
authors.forename: Epameinondas V
authors.initials: EV
authors.lastname: Tsianos
authors.forename: Torben
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authors.lastname: Nathan
authors.forename: Maria
authors.initials: M
authors.lastname: Abreu
authors.forename: Iris
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authors.lastname: Dotan
authors.forename: Bret
authors.initials: B
authors.lastname: Lashner
authors.forename: Jorn
authors.initials: J
authors.lastname: Brynskov
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Terdiman
authors.forename: Peter D R
authors.initials: PD
authors.lastname: Higgins
authors.forename: Maria
authors.initials: M
authors.lastname: Chaparro
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab