Caroline Duley

Patients with Refractory Crohn's Disease Successfully Treated with Ustekinumab.

Background:Ustekinumab is a new biologic therapy targeting interleukin-12 and interleukin -23. It is currently approved for the treatment of psoriasis, but clinical trials have shown that it can induce and maintain remission in Crohns disease (CD). We aim to evaluate effectiveness of ustekinumab in the treatment of CD. Methods:A retrospective chart review was performed including patients (pts) from 2 academic medical centers with complicated, refractory CD started on ustekinumab between June 2011 and June 2014. Pts were treated based on a novel subcutaneous dosing schedule designed to simulate the intravenous load used in clinical trials. Results:Forty-five pts were treated with ustekinumab during this study period. Of the pts who had clinical parameters available before and after medication start, 46% achieved clinical response (Harvey–Bradshaw index decrease ≥3) and 35% achieved clinical remission (Harvey–Bradshaw index ⩽3). Short inflammatory bowel disease questionnaire scores increased significantly (46 [20, 68] to 55 [32, 70], P < 0.05). Erythrocyte sedimentation rate decreased significantly (20 [3, 54] to 12 [0, 42] mm/h, P < 0.05). C-reactive protein decreased significantly (4.9 [0.3, 111] to 3.3 [0.2, 226] mg/L, P < 0.05). Seventy-six percent of patients demonstrated an endoscopic response and 24% achieved complete endoscopic remission. Twelve patients (26%) were hospitalized for IBD-related issues. Four pts had infection-related complications. Six pts (13%) underwent surgery for IBD-related issues. Three pts stopped ustekinumab, 1 for pt preference and 2 for the lack of response. Conclusions:Using a novel subcutaneous dosing schedule, ustekinumab was successful in improving clinical, laboratory, and endoscopic markers of disease activity in patients with severe, refractory CD.

Use of Endoscopic Ultrasound to Guide Adalimumab Treatment in Perianal Crohn's Disease Results in Faster Fistula Healing

Background:Perianal disease is a manifestation of Crohns disease (CD) that has poor long-term treatment outcomes. The aim was to determine if rectal endoscopic ultrasound (EUS)–guided therapy with adalimumab (ADA) can improve outcomes for patients with perianal fistulizing CD. Methods:This is a randomized prospective study comparing serial EUS guidance of fistula treatment versus standard of care in fistulizing perianal CD. At enrollment, all patients underwent a rectal EUS and an EUA with seton placement and/or I&D. Treatment was maximized with immunomodulators, antibiotics, and ADA induction. Surgical interventions were determined by the surgeons discretion in the control group and assisted by every 12th week EUS in the intervention group. Primary and secondary endpoints where complete drainage cessation at week 48 was fistula status per EUS, respectively. Results:Twenty patients were enrolled: 11 control and 9 EUS guidance. At 24 weeks, 7/9 (78%) in EUS group and 3/11 (27%) in control group had drainage cessation (P = 0.04). This significant difference was lost at week 48 (P = 0.44). Three patients in the EUS and 1 in the control group had additional surgical intervention. Those in the EUS group had more rapid escalation of ADA dosing (P = 0.003). There was no difference in the change in PDAI at week 48 versus baseline (P = 0.81). Conclusions:Rectal EUS-guided ADA therapy for CD perianal fistulas showed an initial benefit at 24 weeks, which was lost at week 48. This is likely due to small sample size and higher fistula closure in the controls. However, the faster rate of fistula resolution is a clinically significant finding.

Use of Intravenous Immunoglobulin for Patients with Inflammatory Bowel Disease with Contraindications or Who Are Unresponsive to Conventional Treatments.

Background:Managing patients with IBD who are refractory or have contraindications to standard therapies is challenging. Many will lose response, become intolerant to treatment, or develop infections with contraindication for immunosuppression. Therefore, alternative therapies, such as the use of intravenous immunoglobulin (IVIg), could be used to manage patients in these difficult cases. Methods:Data were extracted retrospectively from the electronic medical records at Vanderbilt University on patients with IBD who received IVIg (February 2011–June 2013). Patients were treated with IVIg 0.4 g·kg−1·d−1 for 3 consecutive days and then 0.4 g/kg once monthly. The dose was increased to 0.4 g/kg biweekly for loss of response or partial response. Clinical response was defined as decreasing the Harvey–Bradshaw Index ≥3 points or improvement in C-reactive protein >25%. Clinical remission was defined as Harvey–Bradshaw Index score <5, no hospitalizations or surgeries after IVIg, or symptom resolution. Statistical analysis was performed using Wilcoxon signed-rank test. Results:Twenty-four patients with IBD received IVIg. Seventeen patients received IVIg for failure of standard treatment. Six patients received IVIg during active infection. Two patients had histoplasmosis, 1 patient had tuberculosis, and 2 patients had pulmonary fungal infections. One patient with ulcerative colitis was given IVIg for recurrent Clostridium difficile. Nine patients required dose escalation after median 153 days (30–360). Ninteen patients (79%) had a response or remission. Sixteen (67%) had a response and 3 (12.5%) obtained remission with IVIg. C-reactive protein decreased significantly after treatment (19 mg/dL [0.1–77] to 7.5 [0.2–20]), P < 0.05. Harvey–Bradshaw Index scores improved (8 [0–19] to 6 [0–17]), P = not significant. Of note, 62.5% had endoscopic improvement after treatment. Conclusions:IVIg is safe and effective in the short-term management of patients with IBD when standard therapies are contraindicated.

Mo1376 Depression and the Cost of Outpatient Treatment of Crohn's Disease in an US Academic Medical Center

Background: There are over 700,000 Americans affected by Crohns disease (CD). A number of previous studies have looked at the cost of treating CD but they have focused primarily on inpatient costs. This study examines the cost of CD treatment in an outpatient setting and the economic burden of the comorbidity of depression among CD patients at a US academic medical center. Method: This is a retrospective study examining hospital cost data of all new patients with CD based on ICD-9 coding seen in an academic medical centers Inflammatory Bowel Disease Center from November 2010-November 2011. Chart review confirmed that billing was only for CDrelated issues. Cost data represent the actual cost to the institution of providing the service and was obtained from the institutions cost accounting database. The presence of depression was measured with the Patient Health Questionnaire-9 (PHQ-9), a self-report instrument used as part of the regular clinical practice in the Inflammatory Bowel Disease (IBD) Center. Multiple regression analysis was used to examine the relationship between patients PHQ-9 score and cost, adjusting for age, race, and gender, as well as an interaction between gender and severity of depression. Results: 650 patients (377 female [58%]) were included in the study. The average age of the patients is 39.7 years [(malesM.39.4 (SD. 15.85) femalesM39.9,( SD. 15.85)]. The average PHQ9 score is 6.80. Females had a higher average PHQ-9 score of 7.80 (SD. 6.40 ) vs. males-

Depression and Inflammatory Bowel Disease Patients: A Tertiary Care Center Experience

G A A b st ra ct s clinical depression was not significant. Using corticosteroids was associated with less fatigue (OR 0.12; 95% CI 0.03-0.52). The different hospitals settings (academic vs general), age and other medication use were not associated with higher fatigue scores. In group B, 545 pts were included (64% female, 77.4% CD, 22.6% UC, mean age 42 (SD 14)) and this group verified the results of group A. However, overall only 60% experienced fatigue and mean CIS score was lower (mean 37 (range 8-56) compared with group A. Furthermore, the use of anti-TNF and male gender were associated with lower percentage of fatigue in CD pts. Conclusion: A high percentage of IBD pts experience severe fatigue. Depression and disease activity were associated with fatigue in these patients. The use of anti-TNF and male gender in CD pts showed the opposite effect and were associated with less fatigue. In UC pts the use of corticosteroids showed less fatigue.

W1310 Split Dosing of Certolizumab Pegol for Crohn's Disease: A Tertiary Care Center Experience

G A A b st ra ct s prevent colectomy. At present it is not known if infliximab, FDA approved for outpatient use, is being employed as an in-hospital “rescue” agent for patients requiring hospitalization. We performed a retrospective analysis of IBD hospitalization records to determine patterns of infliximab use at a tertiary referral institution. Methods: De-identified data from a comprehensive electronic medical record from a single tertiary referral center was reviewed from the years 2002 2008. Patients with IBD were identified with ICD9 codes and indexed terms and these records were reviewed. Demographic and clinical data, history of infections (Clostridium difficile and Cytomegalovirus (CMV)), and treatment records, including use of biologic therapy and colectomy, were recorded. Results: Annual admissions and rates of colectomy were analyzed for the years 2002 2008. Among 216 IBD patients admitted for severe colitis (92% UC, 3% CD, 5% indeterminate colitis) there were 85 colectomies (overall rate 39%; range 28-46% per year). The majority of hospitalized IBD patients did not receive biologic therapy during hospitalization. Rates of biologic therapy during hospitalization rose from 6% in 2002 to 13% in 2008 (peak ultilization 25% in 2003). Overall rates of colectomy among hospitalized IBD patients were similar between patients who received biologic therapy during admission and those who did not. Infectious complications related to IBD were low. Clostridium difficile was identified in 17 patients, 2 of whom required colectomy (6 received infliximab with no colectomies). CMV was identified in 3 patients, all of whom received infliximab and 1 underwent colectomy. Conclusions: Despite the fact that colectomy rates remain unchanged, infliximab is used infrequently in hospitalized IBD colitics. Infectious complications were low in the biologic treated patients and these individuals had low rates of colectomy. Defining algorithms for the optimal use of biologic therapy in hospitalized IBD patients are warranted.