title: Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial.
abstract: OBJECTIVE
  Although the reasons for secondary loss of response to infliximab (IFX) maintenance therapy in Crohn's disease vary, dose intensification is usually recommended. This study investigated the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons for therapeutic failure.
  
  
  METHODS
  Randomised, controlled, single-blind, multicentre study. 69 patients with secondary IFX failure were randomised to IFX dose intensification (5 mg/kg every 4 weeks) (n=36) or interventions based on serum IFX and IFX antibody levels using the proposed algorithm (n=33). Predefined co-primary end points at week 12 were proportion of patients responding (Crohn's Disease Activity Index (CDAI) decrease ≥ 70, or ≥ 50% reduction in active fistulas) and accumulated costs related to treatment of Crohn's disease, expressed as mean cost per patient, based on the Danish National Patient Registry for all hospitalisation and outpatient costs in the Danish healthcare sector.
  
  
  RESULTS
  Costs for intention-to-treat patients were substantially lower (34%) for those treated in accordance with the algorithm than by IFX dose intensification: € 6038 vs € 9178, p<0.001. However, disease control, as judged by response rates, was similar: 58% and 53%, respectively, p=0.81; difference 5% (-19% to 28%). For per-protocol patients, treatment costs were even lower (56%) in the algorithm-treated group (€ 4062 vs € 9178, p<0.001) and with similar response rates (47% vs 53%, p=0.78; difference -5% (-33% to 22%)).
  
  
  CONCLUSIONS
  Treatment of secondary IFX failure using an algorithm based on combined IFX and IFX antibody measurements significantly reduces average treatment costs per patient compared with routine IFX dose escalation and without any apparent negative effect on clinical efficacy.
  
  
  BACKGROUND
  NCT00851565.
authors.affiliation: Department of Gastroenterology, Herlev Hospital, , Herlev, Denmark.
authors.forename: Casper
authors.initials: C
authors.lastname: Steenholdt
authors.forename: Jørn
authors.initials: J
authors.lastname: Brynskov
authors.forename: Ole Østergaard
authors.initials: OØ
authors.lastname: Thomsen
authors.forename: Lars Kristian
authors.initials: LK
authors.lastname: Munck
authors.forename: Jan
authors.initials: J
authors.lastname: Fallingborg
authors.forename: Lisbet Ambrosius
authors.initials: LA
authors.lastname: Christensen
authors.forename: Gitte
authors.initials: G
authors.lastname: Pedersen
authors.forename: Jens
authors.initials: J
authors.lastname: Kjeldsen
authors.forename: Bent Ascanius
authors.initials: BA
authors.lastname: Jacobsen
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Oxholm
authors.forename: Jakob
authors.initials: J
authors.lastname: Kjellberg
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Mark Andrew
authors.initials: MA
authors.lastname: Ainsworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D003362:Cost-Benefit Analysis; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000191:economics; D003718:Denmark; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D000069285:Infliximab; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine / Q000191:economics*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: COST-EFFECTIVENESS; CROHN'S DISEASE; IBD CLINICAL; INFLIXIMAB; TNF