title: Exploring the use of adalimumab for patients with moderate Crohn's disease: subanalyses from induction and maintenance trials.
abstract: BACKGROUND
  Anti-TNF agents are often reserved for patients with severe Crohn's disease (CD).
  
  
  OBJECTIVE
  We explored the predictive value of baseline disease activity and C-reactive protein (CRP) for disease course, adalimumab efficacy for remission (induction and maintenance) in patients with moderate and severe CD, and adalimumab efficacy in moderate CD by CRP category.
  
  
  METHODS
  Post hoc analyses of remission data were performed for all randomized patients from induction (CLASSIC I) and maintenance (CHARM, EXTEND) adalimumab trials in patients with moderate (CDAI≤300) or severe (CDAI>300) CD, and in high (≥10 mg/L) or low (<10 mg/L) CRP moderate CD subgroups. Placebo-treated CHARM patients were evaluated for disease activity over time and time to CD-related hospitalization, by baseline disease severity and CRP.
  
  
  RESULTS
  Moderate CD patients had the highest clinical remission rate and largest treatment effect size compared with placebo at week 4 after 160/80 mg induction (46.3% adalimumab, 17.4% placebo; versus 22.9%, 3.6% for severe patients). Moderate-CD/high-CRP patients had the most pronounced efficacy (57.1% adalimumab, 6.7% placebo; versus 40.7%, 20.0% for lower CRP group). Adalimumab maintenance treatment (40 mg every-other-week) achieved superior remission versus placebo at one year in moderate (32.9% versus 13.7%) and severe (27.2% versus 7.5%) cohorts. Among moderate patients, efficacy was similar by CRP category. Moderate-CD/high-CRP placebo-treated patients experienced disease activity and hospitalization rates at week 56 of CHARM approaching those of severe CD patients.
  
  
  CONCLUSIONS
  This analysis suggests that moderate CD patients can be treated effectively with adalimumab, and supports using CRP to identify moderate CD patients at greatest risk of disease progression.
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. Electronic address: wsandborn@ucsd.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.forename: Julian
authors.initials: J
authors.lastname: Panés
authors.forename: Majin
authors.initials: M
authors.lastname: Castillo
authors.forename: Anne M
authors.initials: AM
authors.lastname: Robinson
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Roopal
authors.initials: R
authors.lastname: Thakkar
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism*; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012074:Remission Induction; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D002097:C-Reactive Protein; D000068879:Adalimumab
keywords: Adalimumab;; Anti-tumor necrosis factor therapy;; C-reactive protein;; Crohn's disease;; Inflammatory bowel disease