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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 Crohn's disease (CD). We aim to evaluate effectiveness of ustekinumab in the treatment of CD.MethodsA 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.ResultsForty-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.ConclusionsUsing a novel subcutaneous dosing schedule, ustekinumab was successful in improving clinical, laboratory, and endoscopic markers of disease activity in patients with severe, refractory CD.

Abstract Background Prior research demonstrates Crohn’s disease patients often do well in pregnancy; however, less is known about the risk of flare in the postpartum period. Methods A retrospective chart review was conducted at a tertiary care inflammatory bowel disease center. All pregnant women with Crohn’s disease who were followed in the postpartum period, defined as 6 months after delivery, were included. Statistical analysis included χ 2 analysis, Wilcoxon rank sum test, and logistic regression analysis. The primary outcome of interest was rate of flare in the postpartum period. Results There were 105 patients included in the study, with a majority (68%) on biologic medication during pregnancy. Thirty-one patients (30%) had a postpartum flare at a median of 9 weeks (range 2–24 weeks). Twenty-five patients (81%) had their postpartum flare managed in the outpatient setting with medications (only 4 of these patients required prednisone). 6 of 31 patients (19%) were hospitalized at a median of 4 weeks (range 2–26 weeks) after delivery, requiring intravenous corticosteroids or surgery. In multivariable regression, there was no significant increase in risk of postpartum flare with increasing maternal age, flare during pregnancy, or steroid or biologic use during pregnancy. Smoking during pregnancy increased risk of postpartum flare (odds ratio, 16.2 [1.72–152.94], P < 0.05). Conclusion In a cohort of Crohn’s disease patients, 30% experienced a postpartum flare despite being on medical therapy, but most were able to be managed in the outpatient setting.

This study evaluated adherence to self-injectable biologic medications in patients with inflammatory bowel disease and found several factors that increase risk of nonadherence. In Crohn’s disease, these risk factors were additive, meaning as the number of risk factors increased, the likelihood of adherence decreased significantly.AbstractBackgroundIn inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), nonadherence to biologic therapy increases risk of disease flare. The aim of this study was to identify risk factors for nonadherence.MethodsThis was a single-center retrospective study evaluating patients with IBD treated at a tertiary care center and prescribed self-injectable biologic therapy using the center’s specialty pharmacy. Adherence was defined using medication possession ratio (MPR). Nonadherence was defined as MPR <0.86.ResultsFour hundred sixty patients (n = 393 with CD and n = 67 with UC) were evaluated with mean MPR (interquartile range) equaling 0.89 (0.48–1). Overall, 69% of patients were adherent (defined as MPR ≥0.86), 66% of patients with CD and 87% of patients with UC. In univariate analysis, several factors increased risk of nonadherence: CD diagnosis, insurance type, psychiatric history, smoking, prior biologic use, and narcotic use (P < 0.05). In multivariable analysis, Medicaid insurance (odds ratio [OR], 5.5; 95% confidence interval [CI], 1.85–15.6) and CD diagnosis (OR, 2.8; 95% CI, 1.3–6.0) increased risk of nonadherence. In CD, as the number of risk factors increased (narcotic use, psychiatric history, prior biologic use, and smoking), the probability of nonadherence increased. Adherence was 72% in patients with 0–1 risk factors, decreasing to 62%, 61%, and 42% in patients with 2, 3, and 4 risk factors, respectively (P < 0.05).ConclusionsThis study identified risk factors for nonadherence to biologic therapy. In patients with CD, the probability of nonadherence increased as the number of risk factors increased.Video Abstract 10.1093/ibd/izz253_video1Video Abstractizz253media16099897022001

Background Noncompliance in use of anti-tumor necrosis factor (anti-TNF) therapy in patients with moderate-to-severe inflammatory bowel disease (IBD) can be a factor in medication failure. Few studies have evaluated the contribution of depressive symptoms to medication noncompliance in anti-TNF therapies. Methods A retrospective chart review was performed in a single-center tertiary care IBD center for patients with Crohn’s disease and ulcerative colitis starting anti-TNF therapy over a 2-year period. Medication noncompliance was defined as interruption of medication (not filling anti-TNF prescription if injectable or not getting infliximab infusion for 30 days beyond needed date for continuation) due to patient-driven circumstances. Depressive symptoms were evaluated at baseline using the well-validated Patient Health Questionnaire-9 (PHQ-9), with PHQ-9 ≥ 10 indicative of at least moderate depressive symptoms. Statistical analysis was performed using Cox proportional hazards regression controlling for age, sex, psychiatric history, and disease. Results A total of 246 patients (75 with ulcerative colitis, 171 with Crohn’s disease) were started on anti-TNF therapy. Seventy-nine patients (32%) had a prior psychiatric diagnosis reported in the medical record. Thirty-three patients (13%) were noncompliant in follow-up. Sixty patients (24%) had at least moderate depressive symptoms at baseline (PHQ ≥ 10). Depressive symptoms at baseline were significantly associated with noncompliance in follow-up (hazards ratio 2.28, CI 1.1–4.6, p  < 0.05). Conclusion Depressive symptoms at baseline were associated with medication noncompliance of anti-TNF therapies at follow-up when controlling for age, sex, disease type, and history of psychiatric disease.

Introduction Recent research suggests a relationship of inflammatory bowel disease (IBD) and depression. Our objective was to evaluate for improvement of depressive symptoms with treatment of IBD using immunosuppressive medications. Methods A retrospective study of consecutive patients with IBD started on immunosuppressive agents [anti-tumor necrosis factor (anti-TNF) or immunomodulator therapy] was conducted. Patients were evaluated if disease activity indices using Harvey Bradshaw Index for Crohn’s disease (CD) and Simple Clinical Colitis Disease Activity Index for ulcerative colitis (UC) and depressive indices using Patient Health Questionnaire-9 (PHQ-9) scores were obtained before and at least 30 days after initiation of therapy. Results Sixteen patients with UC and 53 patients with CD (all with active disease symptoms) were evaluated over a 60 day median follow-up evaluation (range 30, 140 days). Twenty-two patients started on immunomodulator therapy, and 47 patients started on anti-TNF therapy. Crohn’s disease patients had significantly decreased PHQ-9 scores at follow-up [median 9 (range 3, 14) to 4 (1, 8)], with significant decreases only in those started on anti-TNF therapy. Changes in PHQ-9 and CRP were correlated ( ρ  = 0.38, p  < 0.05). In patients with UC, PHQ-9 scores [5 (3, 9) to 2 (0, 5)] were significantly decreased. Percentage at risk of moderate to severe depression (PHQ-9 scores ≥10) was lower after treatment [Crohn’s disease 51–18 % ( p  < 0.05), ulcerative colitis 18–0 %]. Conclusion Depressive scores decreased significantly in patients with IBD treated with immunosuppressive therapy and the number at risk for moderate to severe depression improved significantly.

Perianal disease is a manifestation of Crohn's 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.MethodsThis 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 surgeon's 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.ResultsTwenty 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).ConclusionsRectal 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.

INTRODUCTION:Iron deficiency anemia (IDA) is a common extra-intestinal complication of inflammatory bowel disease (IBD) which includes both Crohn's disease (CD) and Ulcerative Colitis (UC). The objective of this study was to evaluate the effects of gastroenterologist-led management of IDA in the IBD population.METHODS:A retrospective chart review was conducted at a single tertiary care inflammatory bowel disease center. All patients with proven IBD (CD or UC) and anemia (defined as hemoglobin (Hgb) < 12 for women and <13 for men) treated through the IBD center with standard regimens of intravenous iron (iron sucrose 200 × 5 doses, ferric carboxymaltose 750 mg × 2 doses, ferumoxytol 510 mg × 2 doses) were included. Statistical analysis was performed using paired t test, pearson chi-squared test, and Wilcoxon rank sum test.RESULTS:351 pts (249 pts with CD, 102 pts with UC) were evaluated. Median age was 33 (IQR 25, 46) and 62% were female. The majority of pts (79%, n = 251) had active endoscopic disease prior to treatment for IDA. 60% of pts were on biologic therapy and 27% were on corticosteroids. Hgb and iron increased significantly after iron treatment in both CD and UC as seen in Table 1. SIBDQ improved significantly in both CD and UC as seen in Figure 1. After iron treatment, 41.2% of pts had resolution of IDA. Male pts were more likely to remain anemic than female pts (P = 0.016 using pearson chi-squared test); age and IBD type (CD vs. UC) did not affect anemia persistence. 53% of pts were re-treated with iron infusions. 3% of pts required blood transfusions for IDA. Only 8% of pts required hematology referral.CONCLUSION:In a large cohort of pts with IBD, IDA improves after gastroenterologist-led treatment but persists in the majority of pts, especially male pts. Treatment of IDA improves pts quality of life. Over half of pts required re-treatment. Only a minority of pts required hematology referral for management of IDA.Table 1.Change in Hemoglobin and Iron with IV Iron treatment

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.MethodsData 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.ResultsTwenty-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.ConclusionsIVIg is safe and effective in the short-term management of patients with IBD when standard therapies are contraindicated.

Introduction: Ustekinumab (UST) has been shown to be an effective treatment for maintenance and remission in patients (pts) with moderate to severe Crohn's disease (CD). We aim to evaluate our single center experience with re-induction using subcutaneous (SQ) or intravenous (IV) UST to recapture response and maintain treatment in a subset of pts with refractory CD who had failed prior anti-TNF therapy. Methods: Most pts started UST prior to FDA approval and received induction of UST SQ using novel dosing with UST 90mg SQ at weeks 0, 4, and 12. A majority of pts also received a 270 mg dose at wk 8 of induction (insurance approval dependent). Standard maintenance therapy was 90mg SQ every 8 weeks. If pts had re-induction with UST prior to FDA approval of UST for CD they had a modified re-induction (270mg SQ). After FDA approval, pts received IV doses for re-induction. Statistical analysis was performed using Wilcoxon rank sum testing. Results: 34 pts with CD underwent re-induction with UST. Table 1 summarizes pt characteristics. All pts had been on prior anti-TNF. Total follow up available was 850 days (d) (range 359, 2309 d). Only 2 pts had started UST after FDA approval for use in CD and had IV induction. Reasons for re-induction are summarized in Table 2. 21 pts had a modified re-induction with 270mg SQ dose and 13 pts had IV re-induction. Pts were followed for a median 440 d (range 64, 2196 d) after re-induction. For those with IV re-induction (n=13), follow up was median 282 d (64, 605 d). Only 4 pts discontinued UST after SQ re-induction, at a median of 152 d (118, 210 d) after re-induction. No pts who had IV re-induction had stopped UST by the end of study. 13 pts went to every 4-6 week dosing (4 of those pts with IV re-induction). HBI, CRP decreased in all pts. In 11 pts with IV re-induction, HBI decreased significantly (p <0.05). (Table 3) Ustekinumab levels prior to IV re-induction (n=5) were 1.6ug/mL (0.4, 4.9). 2 pts had levels drawn after re-induction (0.7ug/mL and 3.6ug/mL). 5 pts who had endoscopic inflammation on prior endoscopy were found to be in endoscopic remission, 2 pts had improvement, and 7 pts had no change endoscopically. Conclusion: In summary, re-induction with UST in pts with moderate to severe CD with anti-TNF failure may be an option to recapture response if stopped for loss of response or another reason, such as surgery.