The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Practice Patterns and Predictors of Stopping Colonoscopy in Older Adults With Colorectal Polyps.

BACKGROUND & AIMS: Older adults with colorectal polyps undergo frequent surveillance colonoscopy. There is no specific guidance regarding when to stop surveillance. We aimed to characterize endoscopist recommendations regarding surveillance colonoscopy in older adults and identify patient, procedure, and endoscopist characteristics associated with recommendations to stop. METHODS: This was a retrospective cohort study at a single academic medical center of adults aged ≥75 years who underwent colonoscopy for polyp surveillance or screening during which polyps were found. The primary outcome was a recommendation to stop surveillance. Predictors examined included patient age, sex, family history of colorectal cancer, polyp findings, and endoscopist sex and years in practice. Associations were evaluated using multilevel logistic regression. RESULTS: Among 1426 colonoscopies performed by 17 endoscopists, 34.6% contained a recommendation to stop and 52.3% to continue. Older patients were more likely to receive a recommendation to stop, including those 80-84 years (odds ratio [OR], 7.7; 95% confidence interval [CI], 4.8-12.3) and ≥85 years (OR, 9.0; 95% CI, 3.3-24.6), compared with those 75-79 years. Family history of colorectal cancer (OR, 0.42; 95% CI, 0.24-0.74) and a history of low-risk (OR, 0.17; 95% CI, 0.11-0.24) or high-risk (OR, 0.02; 95% CI, 0.01-0.04) polyps were inversely associated with recommendations to stop. The likelihood of a recommendation to stop varied significantly across endoscopists. CONCLUSIONS: Only 35% of adults ≥75 years of age are recommended to stop surveillance colonoscopy. The presence of polyps was strongly associated with fewer recommendations to stop. The variation in endoscopist recommendations highlights an opportunity to better standardize recommendations following colonoscopy in older adults.

Hemophagocytic Lymphohistiocytosis Occurring in Inflammatory Bowel Disease: Systematic Review.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive syndrome of excessive cytokine requiring prompt recognition and aggressive therapy. AIMS: We aimed to systematically characterize HLH in moderate-to-severe inflammatory bowel disease (IBD). METHODS: We performed a systematic review of the literature (PubMED; EMBASE) and FDA Adverse Event Reporting System in accordance with the PRISMA statement. Use of biologics was used as a surrogate definition for disease severity (consistent with usual and contemporary clinical management), to enable identification of rare HLH cases with the highest fidelity. RESULTS: 58 cases of HLH occurring in IBD patients are known (mean age: 26.0 years, 70% male, 83% with Crohn's disease, mean disease duration 7.0 years). 34.5% of patients were undergoing induction therapy at HLH diagnosis. All cases occurred on patients exposed to anti-TNF agents, but cases with anti-integrin or anti-IL-12/23 exposure were reported. 2/3 of cases did not report prior AZA/6MP exposure. Underlying opportunistic infection or lymphoma was found in > 80% of cases. Survival was 70% if promptly recognized and treated. Five patients restarted biologics after HLH resolved, and one patient developed recurrent HLH. CONCLUSIONS: HLH is rare among IBD patients exposed to biologic therapy. Most cases had an identifiable infection or malignancy at the time of diagnosis as well as history of immunomodulator use. Risk factors may include younger age, male gender, presence of Crohn's disease, and induction phase of treatment. Our study is not intended to assess risk of HLH with specific IBD therapies.

The management of the hospitalized ulcerative colitis patient: the medical-surgical conundrum.

PURPOSE OF REVIEW: In this review article, we address emerging evidence for the medical and surgical treatment of the hospitalized patient with ulcerative colitis. RECENT FINDINGS: Ulcerative colitis is a chronic inflammatory disease involving the colon and rectum. About one-fifth of patients will be hospitalized from ulcerative colitis, and about 20-30%, experiencing an acute flare will undergo colectomy. Because of the significant clinical consequences, patients hospitalized need prompt evaluation for potential complications, stratification of disease severity, and a multidisciplinary team approach to therapy, which involves both the gastroenterologist and surgeon. Although corticosteroids remain first-line therapy, second-line medical rescue options, primarily infliximab or cyclosporine, are considered within 3-5 days of presentation. In conjunction, an early surgical consultation to present the possibility of a staged proctocolectomy as one of the therapeutic options is equally important. SUMMARY: A coordinated multidisciplinary, individualized approach to treatment, involving the patient preferences throughout the process, is optimal in providing patient-centered effective care.

Testing and Treating Small Intestinal Bacterial Overgrowth Reduces Symptoms in Patients with Inflammatory Bowel Disease.

BACKGROUND: Common mechanisms against small intestinal bacterial overgrowth (SIBO), including an intact ileocecal valve, gastric acid secretion, intestinal motility, and an intact immune system, are compromised in inflammatory bowel disease (IBD), and therefore, a relatively high incidence of SIBO has been reported in this population. AIMS: We aimed to determine whether an improvement in IBD clinical activity scores is seen after testing and treating SIBO. METHODS: A retrospective cohort study of 147 patients with inflammatory bowel disease who were referred for SIBO breath testing from 1/2012 to 5/2016 was performed. Characteristics of SIBO positive and treated patients were compared to SIBO negative patients, including the changes in Partial Mayo Score or Harvey Bradshaw Index (HBI), using Student's t test for continuous variables and Chi-squared or Fisher's exact test for categorical variables. RESULTS: 61.9% were SIBO positive and treated, and 38.1% were SIBO negative. In Crohn's disease, the median HBI decreased from 5 to 3 and 5 to 4, in the SIBO positive and negative groups, respectively (p = 0.005). In ulcerative colitis, the Partial Mayo Score decreased from 2 to 1.5 and 2 to 1, respectively (p = 0.607). CONCLUSIONS: This study examines the clinical effect of testing and treating for SIBO in an IBD population. We see a significant reduction in HBI after testing for and treating SIBO. Future prospective studies are necessary to further investigate the role of SIBO in the evaluation and management of IBD.

Systematic review: hepatosplenic T-cell lymphoma on biologic therapy for inflammatory bowel disease, including data from the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare, poorly treatable malignancy associated with therapy for IBD. Current knowledge of HSTCL risk in IBD comes from an era of step-up therapy, before earlier use of biologics or combination therapy was advocated to achieve deep mucosal healing. HSTCL risk among newer biologic classes has also not been evaluated. AIMS: To systematically characterise the association of HSTCL with biologic therapy for IBD. METHODS: We conducted a literature search and query of the Food and Drug Administration Adverse Event Reporting System to summarise HSTCL cases among IBD patients with prior biologic exposure. Demographics and immunosuppression exposure were extracted. Patients were stratified by current regimen (combination therapy, biologic monotherapy or no biologic), and biologic class (anti-TNF, anti-integrin, anti-interleukin 12/23). RESULTS: Sixty-two cases of HSTCL were identified from 2486 abstracts and 181 FDA Adverse Events Reporting System reports. The median age of affected patients was 28 years (range 12-81), and 83.6% were male, 84.7% had Crohn's disease. Five of 62 patients had no reported azathioprine/mercaptopurine exposure. Three patients within the cohort developed HSTCL after exposure to natalizumab, vedolizumab or ustekinumab; all three also had anti-TNF and azathioprine/mercaptopurine exposure. Forty-three of 49 (87.8%) patients with known outcomes died with a median survival of 5 months. CONCLUSIONS: Consistent with existing data, almost all identified HSTCL cases among IBD patients on biologic therapy had azathioprine/mercaptopurine exposure, and all cases on patients exposed to biologics had anti-TNF exposure. These data suggest initiating a patient-centred discussion before starting anti-TNF therapy or other biologics.

Escalation of Immunosuppressive Therapy for Inflammatory Bowel Disease Is Not Associated With Adverse Outcomes After Infection With Clostridium difficile.

BACKGROUND: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy. METHODS: This multicenter retrospective cohort study included IBD patients with documented CDI at 4 academic medical centers. Data were abstracted from clinical databases at each institution. Outcomes at 30 and 90 days were compared between patients undergoing new or intensified immunosuppressive therapy and those without therapy escalation. Continuous variables were compared using t tests, and proportions using chi-square tests. Multivariable logistic regression was used to determine the association of individual variables with severe outcomes (including death, sepsis, and/or colectomy) within 90 days. Secondary outcomes included CDI recurrence, rehospitalization, worsening of IBD, and severe outcomes within 30 days. RESULTS: A total of 207 adult patients with IBD and CDI were included, of whom 62 underwent escalation to biologic or corticosteroid therapy (median time to escalation, 13 days). Severe outcomes within 90 days occurred in 21 (15.6%) nonescalated and 1 (1.8%) therapy-escalated patients. Serum albumin <2.5 mg/dL, lactate >2.2 mg/dL, intensive care unit admission, hypotension, and comorbid disease were associated with severe outcomes. Likelihood of severe outcomes was decreased in patients undergoing escalation of IBD therapy after CDI (adjusted odds ratio [aOR], 0.12) and increased among patients aged >65 years (aOR, 4.55). CONCLUSIONS: Therapy escalation for IBD within 90 days of CDI was not associated with worse clinical outcomes. Initiation of immunosuppression for active IBD may therefore be appropriate in carefully selected patients after treatment of CDI.

Comprehensive review of the prognostic value of galectin-3 in heart failure.

Heart failure (HF) is a major cause of morbidity and mortality in the United States; however, reliable biomarkers predicting outcomes of patients suffering from HF are still not available. Finding a prognostic indicator in patients with HF could ultimately help improve the quality of goal-directed care for these patients. A number of recent studies suggest that galectin-3, a peptide that has been repeatedly shown to be elevated in the setting of inflammatory processes, may provide information regarding the pathophysiologic process underlying HF. If this is the case, galectin-3 may independently be able to provide more information regarding prognosis in patients with HF than some of the more conventional indicators currently in use today (ie, natriuretic peptide, C-reactive protein). We analyzed the most recent and comprehensive studies that have looked at the utility of galectin-3 as a prognostic marker in patients with HF. After a thorough review, we found that the evidence against the use of galectin-3 as a prognostic biomarker in HF was too strong to support its routine use in current clinical settings. However, many of the studies, both in support of and in opposition to the prognostic potential of galectin-3, were uniformly limited by undersized cohorts, and thus the need for further exploration is clearly warranted.