title: Dosage adjustment during long-term adalimumab treatment for Crohn's disease: clinical efficacy and pharmacoeconomics.
abstract: BACKGROUND
  Data from CHARM, a 56-week, randomized controlled trial of adalimumab for patients with moderately to severely active Crohn's disease (CD), were used to evaluate outcomes of adalimumab dosage adjustment.
  
  
  METHODS
  Patients randomized to blinded adalimumab 40 mg every other week (EOW) in CHARM were the focus of the analysis. At ≥12 weeks, patients with flares or lack of response versus baseline (including patients who responded and then lost response) could move sequentially to open-label (OL) adalimumab EOW and then to OL adalimumab weekly.
  
  
  RESULTS
  Of 260 patients randomized to adalimumab EOW, 140 (54%) continued blinded EOW therapy and 120 (46%) moved to OL therapy. Of patients on OL therapy, 49 (19%) continued EOW therapy and 71 (27%) moved to weekly therapy; 36 (14%) completed the trial on weekly therapy. Of 71 patients on weekly therapy, 37% achieved clinical remission (Crohn's Disease Activity Index [CDAI] <150), 58% achieved CR-100 (CDAI decreased ≥100 points), and 63% achieved CR-70 (CDAI decreased ≥70 points). Of the 49 patients who remained on OL EOW therapy, 39% achieved clinical remission, 59% achieved CR-100, and 63% achieved CR-70. In a logistic regression, greater baseline CDAI predicted changing to weekly therapy. A model of dosage-adjustment cost indicated a modest per-patient drug-acquisition cost increase ($574 over yearly EOW dosing cost [$22,518]).
  
  
  CONCLUSIONS
  Of patients randomized to blinded EOW therapy, 19% moved to OL EOW therapy and 27% moved to OL weekly therapy for flares or lack of response versus baseline. Weekly therapy was associated with clear clinical benefits and a small cost increase.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. sandborn.william@mayo.edu
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Scott E
authors.initials: SE
authors.lastname: Plevy
authors.forename: Paul F
authors.initials: PF
authors.lastname: Pollack
authors.forename: Anne M
authors.initials: AM
authors.lastname: Robinson
authors.forename: Jingdong
authors.initials: J
authors.lastname: Chao
authors.forename: Parvez
authors.initials: P
authors.lastname: Mulani
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000191:economics; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000191:economics*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy* / Q000191:economics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017850:Economics, Pharmaceutical; D005260:Female; D006801:Humans; D008134:Long-Term Care; D008297:Male; D010919:Placebos; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab