P243. Subgroup analysis of the placebo-controlled CHARM trial: Increased remission rates for adalimumab-treated patients with early Crohn's disease
S. Schreiber1, W. Reinisch2, J.‑F. Colombel3, W. Sandborn4, A. Robinson5, B. Huang5, K. Lomax5, P. Pollack5
1University Hospital of Schleswig-Holstein, Department of General Internal Medicine, Kiel, Germany; 2AKH Wien, Department of Internal Medicine IV, Vienna, Austria; 3Centre Hospitalier Universitaire de Lille, Hôpital Claude Huriez, Lille, France; 4University of California, San Diego, La Jolla, United States; 5Abbott Laboratories, Illinois, United States
Background: We examined the impact of disease duration on clinical outcomes and safety in patients treated with adalimumab for moderate to severe CD.
Methods: The effect of potential predictive factors on remission in adalimumab-treated patients at week 56 was assessed using logistic regression. Continuous variables included were: age; baseline C‑reactive protein (CRP); baseline CDAI; and disease duration. Categorical variables included were: tobacco use (former smoker, never smoked, current smoker); baseline fistula; baseline use of immunosuppressants, steroids, or aminosalicylates; and previous use of anti‑TNF therapy, immunosuppressants, or steroids. For this post hoc analysis, all randomized patients in the CHARM trial were divided into 3 disease duration categories: <2 (n = 93), 2 to <5 (n = 148), and ≥ 5 years (n = 536). Clinical remission rates at week 56 were also compared between adalimumab and placebo in each disease duration subgroup. Incidence of adverse events (AEs) in adalimumab-treated patients was evaluated.
Results: Logistic regression confirmed shorter disease duration as a significant predictor for higher remission rate at week 56 in adalimumab-treated patients (odds ratio [OR]/year of disease = 0.974, 95% CI =0.950, 1.000; P = 0.046). Baseline CRP, baseline CDAI, baseline aminosalicylate use, and previous anti‑TNF use were also significant predictive factors in the final regression model at week 56 in adalimumab-treated patients. At week 56, clinical remission rates were significantly greater for adalimumab-treated vs. placebo-treated patients in all subgroups (43% vs. 19% for <2 years, P < 0.024; 30% vs. 13% for 2 to <5 years, P = 0.028; 28% vs. 8% for ≥5 years, P < 0.001). The safety profile was generally similar across the duration categories; the incidence of serious AEs (including serious infections) was greatest in patients with disease duration ≥5 years.
Conclusions: In the CHARM trial in patients with moderate to severe CD, adalimumab treatment led to statistically significantly greater rates of clinical remission after 1 year of treatment than placebo, regardless of disease duration. Clinical remission rates were higher in the shortest disease duration subgroup, and disease duration was a significant predictor for achievement of clinical remission. However, as disease duration is related to other clinical confounders, prospective studies are needed to confirm the positive benefit-risk profile of anti‑TNF therapy in early CD that is suggested by this analysis.