C-Reactive Protein Levels in Moderate to Severe Crohnʼs Disease Patients Decreased Rapidly and Significantly During Adalimumab Therapy

Abstract

Purpose: C-reactive protein (CRP) is a plasma protein involved in the acute phase of inflammatory response. In patients with Crohn's disease (CD), CRP level provides a useful biologic marker for monitoring disease progression and treatment efficacy. Methods: We examined the effect of adalimumab induction therapy on rapid reduction in CRP levels among patients with moderate to severe CD (Crohn's Disease Activity Index [CDAI] 220-450), as well as moderate CD (baseline CDAI <300) only. The study used data from CHARM, a Phase III trial in which all patients received adalimumab 80 mg at baseline (Week 0) and 40 mg at Week 2 before being randomized to placebo or continuing adalimumab treatment at Week 4. Within the intent-to-treat sample (N=778), analyses included patients who had a CRP value recorded at both baseline and Week 2; patients without a CRP measurement at Week 4 had their Week-2 value carried forward. Mean changes in CRP from baseline to Weeks 2 and 4 were evaluated for statistical significance using paired Student t-tests. McNemar's tests were used to assess changes in the proportion of patients with elevated CRP (>1 mg/dL) from baseline to Weeks 2 and 4. As a subgroup analysis, CRP outcomes were also evaluated among patients with moderate CD. Results: At baseline, CRP levels (mean±standard deviation) were 2.15±3.28 mg/dL among patients with moderate to severe CD (N=767) and 1.63±2.22 among patients with moderate CD (N=367). After adalimumab induction therapy, mean changes from baseline in CRP were statistically significant by Week 2 (-1.26±2.96) and Week 4 (-0.97±3.14) in the overall sample (both p<0.001). The proportion of patients with CRP >1 mg/dL decreased from 46.4% at baseline to 21.3% at Week 2 and 24.1% at Week 4 (both p<0.001 vs. baseline). In the subset of patients with moderate CD, CRP decreased by an average of -0.93±1.84 and -0.60±2.09 from baseline to Weeks 2 and 4, respectively (both p<0.001). Significantly fewer patients with moderate CD showed elevated CRP at Weeks 2 and 4 compared to baseline (15.5% and 20.7% vs. 41.4%; both p<0.001). Among patients with elevated CRP at baseline but not Week 4 (N=189), remission rate at Week 52 was 35.8% for the adalimumab arm eow+weekly vs. 9.1% for the placebo arm (p<0.001). Conclusion: Adalimumab was associated with rapid and statistically significant reductions in CRP within 4 weeks among patients with moderate to severe CD. Similar decreases in CRP were observed among patients with moderate CD. Disclosure: Dr. S Ghosh - Advisory Board: Abbott, Centocor, Merck, Pfizer, Shire; Honoraria for Lecturing in Educational Events: Abbott, Merck, Shire; Research Support: Abbott, Merck. Drs. EQ Wu & AG Bensimon - Employee: Analysis Group, under contract with Abbott. Drs. PM Mulani, M Yang, & J Chao - Employee and Stockholder: Abbott.