BACKGROUND: Anti-TNF agents are often reserved for patients with severe Crohn's disease (CD). AIMS: 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.
RCT Entities:
BACKGROUND: Anti-TNF agents are often reserved for patients with severe Crohn's disease (CD). AIMS: 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 CDpatients 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-CRPpatients 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 CDpatients. CONCLUSIONS: This analysis suggests that moderate CDpatients can be treated effectively with adalimumab, and supports using CRP to identify moderate CDpatients at greatest risk of disease progression.
Authors: E G Quetglas; A Armuzzi; S Wigge; G Fiorino; L Barnscheid; M Froelich; Silvio Danese Journal: Eur J Clin Pharmacol Date: 2015-05-27 Impact factor: 2.953
Authors: G Monteleone; A Di Sabatino; S Ardizzone; F Pallone; K Usiskin; X Zhan; G Rossiter; M F Neurath Journal: Aliment Pharmacol Ther Date: 2016-01-13 Impact factor: 8.171