title: Prediction of Short- and Medium-term Efficacy of Biosimilar Infliximab Therapy. Do Trough Levels and Antidrug Antibody Levels or Clinical And Biochemical Markers Play the More Important Role?
abstract: OBJECTIVE
  Biosimilar infliximab CT-P13 received European Medicines Agency [EMA] approval in June 2013 for all indications of the originator product. In the present study, we aimed to evaluate the predictors of short- and medium-term clinical outcome in patients treated with the biosimilar infliximab at the participating inflammatory bowel disease [IBD] centres in Hungary.
  
  
  METHODS
  Demographic data were collected and a harmonised monitoring strategy was applied. Clinical and biochemical activities were evaluated at Weeks 14, 30, and 54. Trough level [TL] and anti-drug antibody [ADA] concentrations were measured by enzyme-linked immunosorbent assay [ELISA] [LT-005, Theradiag, France] at baseline at 14, 30 and 54 weeks and in two centres at Weeks 2 and 6.
  
  
  RESULTS
  A total of 291 consecutive IBD patients (184 Crohn's disease [CD] and 107 ulcerative colitis [UC]) were included. In UC, TLs at Week 2 predicted both clinical response and remission at Weeks 14 and 30 (clinical response/remission at Week 14: area under the curve [AUC] = 0.81, p < 0.001, cut-off: 11.5 μg/ml/AUC = 0.79, p < 0.001, cut-off: 15.3μg/ml; clinical response/remission at Week 30: AUC = 0.79, p = 0.002, cut-off: 11.5 μg/ml/AUC = 0.74, p = 0.006, cut-off: 14.5 μg/ml), whereas ADA positivity at Week 14 was inversely associated with clinical response at Week 30 [58.3% vs 84.8% ,p = 0.04]. Previous anti-tumour necrosis factor [TNF] exposure was inversely associated with short-term clinical remission [Week 2: 18.8% vs 47.8%, p = 0.03, at Week 6: 38.9% vs 69.7%, p = 0.013, at Week 14: 37.5% vs 2.5%, p = 0.06]. In CD, TLs at Week 2 predicted short-term [Week 14 response/remission, AUCTLweek2 = 0.715-0.721, p = 0.05/0.005] but not medium-term clinical efficacy. In addition, early ADA status by Week 14 [p = 0.04-0.05 for Weeks 14 and 30], early clinical response [p < 0.001 for Weeks 30/54] and normal C-reactive protein [CRP] at Week 14 [p = 0.005-0.0001] and previous anti-TNF exposure [p = 0.03-0.0001 for Weeks 14, 30, and 54] were associated with short-and medium-term clinical response and remission.
  
  
  CONCLUSIONS
  In UC, early TLs were predictive for short- and medium-term clinical efficacy, whereas in CD, Week 2 TLs were associated only with short-term clinical outcomes.
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Lorant
authors.initials: L
authors.lastname: Gonczi
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Vegh
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Petra Anna
authors.initials: PA
authors.lastname: Golovics
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Mariann
authors.initials: M
authors.lastname: Rutka
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Krisztina Barbara
authors.initials: KB
authors.lastname: Gecse
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Renata
authors.initials: R
authors.lastname: Bor
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Farkas
authors.affiliation: Military Hospital - State Health Centre, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Szamosi
authors.affiliation: First Department of Medicine, Peterfy Hospital, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Bene
authors.affiliation: Second Department of Medicine, Zala County Hospital, Zalaegerszeg, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Gasztonyi
authors.affiliation: Second Department of Medicine, B-A-Z County and University Teaching Hospital, Miskolc, Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Kristóf
authors.affiliation: Department of Internal Medicine, Csolnoky Ferenc Regional Hospital, Veszprém, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Lakatos
authors.affiliation: Second Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Miheller
authors.affiliation: Institute of Medicine, Department of Gastroenterology, University of Debrecen, Clinical Center, Debrecen, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Palatka
authors.affiliation: Institute of Medicine, Department of Gastroenterology, University of Debrecen, Clinical Center, Debrecen, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Papp
authors.affiliation: Department of Medicine and Gastroenterology, Markusovszky Hospital, Szombathely, Hungary.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Patai
authors.affiliation: Department of Gastroenterology, Tolna County Teaching Hospital, Szekszárd, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Salamon
authors.affiliation: Department of Gastroenterology, Janos Hospital, Budapest, Hungary.
authors.forename: Gábor Tamás
authors.initials: GT
authors.lastname: Tóth
authors.affiliation: First Department of Medicine, University of Pécs, Pécs, Hungary.
authors.forename: Áron
authors.initials: Á
authors.lastname: Vincze
authors.affiliation: Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Edina
authors.initials: E
authors.lastname: Biro
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Barbara Dorottya
authors.initials: BD
authors.lastname: Lovasz
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kurti
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szepes
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Molnár
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Péter L
authors.initials: PL
authors.lastname: Lakatos
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D015415:Biomarkers; D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D008297:Male; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D059451:Biosimilar Pharmaceuticals; C000591237:CT-P13; D005765:Gastrointestinal Agents; D002097:C-Reactive Protein; D000069285:Infliximab
keywords: Biosimilar infliximab; inflammatory bowel diseases