The Importance of Monitoring the Postpartum Period in Moderate to Severe Crohn's Disease.

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.

A Single Center Experience With Long-Term Ustekinumab Use and Reinduction in Patients With Refractory Crohn Disease.

BACKGROUND: Ustekinumab was approved for moderate and severe Crohn's disease (CD) in 2016, but little is known about long-term outcomes. METHODS: A retrospective study evaluated all patients with CD treated with ustekinumab, including patients with reinduction. C-reactive protein (CRP), Harvey-Bradshaw Index (HBI), Short Inflammatory Bowel Disease (SIBDQ), and endoscopy outcomes were collected prospectively. RESULTS: Ninety-six patients received ustekinumab, resulting in improvement in CRP, HBI, and SIBDQ scores with 68% endoscopic improvement/remission. Thirty-four patients underwent reinduction, resulting in improved HBI and CRP. CONCLUSIONS: Ustekinumab in refractory CD results in significant clinical and endoscopic improvement and reinduction may be a viable option to recapture response.

Risk Factors for Medication Nonadherence to Self-Injectable Biologic Therapy in Adult Patients With Inflammatory Bowel Disease.

BACKGROUND: In 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. METHODS: This 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. RESULTS: Four 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). CONCLUSIONS: This 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.

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 Crohn's 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 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. 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 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. 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·d 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.

Review article: multiple myeloma and inflammatory bowel disease.

Since 1964 only nine cases of multiple myeloma occurring in the setting of inflammatory bowel disease have been reported. Although this occurrence may be a mere unfortunate coincidence, there are sound pathophysiological reasons for such an event. The possibility that chronic inflammatory conditions, immunomodulator therapy, and infliximab can predispose to multiple myeloma and lymphoma is reviewed. We discuss in detail the only reported case of multiple myeloma arising in the setting of infliximab treatment for Crohn's disease. It is highly probable that infliximab therapy had a causal role in our patient developing multiple myeloma. The pathogenesis of multiple myeloma arising in the setting of infliximab therapy may be related to decreased apoptosis of plasma cell populations. Since it is possible that a causal association exists between infliximab therapy and multiple myeloma, additional screening measures may be required in patients with Crohn's disease on infliximab.