Clinical Response to Ustekinumab in Crohnʼs Disease: Results from an Academic Inflammatory Bowel Disease Center

Abstract

Purpose: Ustekinumab is a novel fully humanized IgG1 antibody that is able to disrupt IL-12/23 signaling by blocking the activity of the common p40 subunit. It has recently been found to decrease Crohn's disease (CD) activity in patients who have failed anti-TNF therapy. The goal of this study was to assess the role of open label ustekinumab in the clinical treatment of CD patients. Methods: We conducted a retrospective review of all available (n=48) CD patients receiving ustekinumab at our IBD Center. Demographics, disease characteristics (Montreal classification), previous and concurrent therapies, a prospectively calculated Harvey Bradshaw Index (HBI), and serum levels of C-reactive protein (CRP) were obtained from an electronic record review. Those patients who had been on ustekinumab for at least 6 months were included in our analysis. A two-tailed paired t-test or a Wilcoxon signed rank test was used depending on results of D'Agostino-Pearson normality test. Results: Of 40 patients included, 67.5% were female. The median age at first dose of ustekinumab was 32 years (range 19-73). 57.5% had L1 ileal disease and 90% had L2 or L3 colonic disease. 100% of the study cohort had failed at least one previous anti-TNF therapy (82.5% infliximab, 61.5% adalimumab, and 66.7% certolizumab). At 3 months after initiation of therapy, there was a statistically significant decrease in median HBI (p=0.004 and p<0.0001) from 9 (6.75 to 13.00) at baseline to 4 (2.00 to 5.00) and 4 (3.00 to 7.00) at 3 and 6 months, respectively. There was also a significant decrease (p=0.02) in CRP from a median (interquartile range) of 1.6 (0.80 to 5.8) to 0.85 (0.58 to 1.55) (See Figure). Subgroup comparisons based on site of CD activity, concurrent antibiotic, steroid, and salicylate use showed a statistically significant decrease in CRP at 3 months in those with only L2 colonic disease. In all subgroups there was a statistically significant decrease in HBI at 3 and 6 months. Adverse events were seen in 19 patients, including arthralgias (4), worsening strictures (3), and gastrointestinal bleeding (2).FigureConclusion: Ustekinumab can successfully induce remission in patients who have previously failed anti-TNF therapy. There is a decrease in both CRP and HBI at 3 and 6 months. Our small sample size precludes the ability to determine factors which might predict response. The role of this drug in clinical practice continues to need further investigation.