Crohn's disease shared decision making intervention leads to more patients choosing combination therapy: a cluster randomised controlled trial.

BACKGROUND: Crohn's disease requires effective patient-clinician communication for successful illness and medication management. Shared decision making (SDM) has been suggested to improve communication around early intensive therapy. However, effective evidence-based SDM interventions for Crohn's disease are lacking, and the impact of SDM on Crohn's disease decision making and choice of therapy is unclear. AIM: To test the impact of SDM on choice of therapy, quality of the decision and provider trust compared to standard Crohn's disease care. METHODS: We conducted a multi-site cluster randomised controlled trial in 14 diverse gastroenterology practices in the US. RESULTS: A total of 158 adult patients with Crohn's disease within 15 years of their diagnosis, with no prior Crohn's disease complications, and who were candidates to receive immunomodulators or biologics, participated in the study. Among these, 99 received the intervention and 59 received standard care. Demographics were similar between groups, although there were more women assigned to standard care, and a slightly shorter disease duration among those in the intervention group. Participants in the intervention group more frequently chose combination therapy (25% versus 5% control, p < 0.001), had a significantly lower decisional conflict (p < 0.05) and had greater trust in their provider (p < 0.05). CONCLUSIONS: With rapidly expanding medication choices for Crohn's disease and slow uptake of early intensive therapy, SDM can personalise treatment strategies and has the potential to move the field of Crohn's disease management forward with an ultimate goal of consistently treating this disease early and intensively in appropriate patients. TRIAL REGISTRATION: Evaluating a Shared Decision Making Program for Crohn's Disease, ClinicalTrials.gov Identifier NCT02084290 https://clinicaltrials.gov/ct2/show/NCT02084290.

Perspectives From Patients and Gastroenterologists on De-escalating Therapy for Crohn's Disease.

In Crohn's disease, combination therapy with anti-tumor necrosis factor (anti-TNF) agents and azathioprine/mercaptopurine has been shown to be superior to monotherapy with one of these treatments alone.1 This combination has its best success rate when used early in the course of treatment.2 However, because of the significant cost of these drugs and concerns over long-term side effects,3,4 many patients and providers often ask about stopping one or both of these medications.

Patients' Perceive Biologics to Be Riskier and More Dreadful Than Other IBD Medications.

BACKGROUND: Biologic medications have advanced the management of inflammatory bowel diseases (IBD) but are underutilized in the treatment algorithm. One reason may be related to patients' concerns about adverse events and their perceptions of risk. The aim of this study was to compare patients' perceptions of risk of IBD treatment with their perceived risk of everyday occurrences and other medications and how these perceptions may be influenced by personality traits. METHODS: A cross-sectional study of consecutive IBD patients was conducted at a single tertiary care center. Participants were asked to report about their perception of risk of IBD medications, non-IBD medications, invasive procedures, and everyday life occurrences. Participants responded also to the Multidimensional Health Locus of Control (MHLC) scale to characterize beliefs about control over health outcomes. RESULTS: A total of 130 patients with IBD completed the questionnaires. There was a broad range of disease severity and prior medication use. Biologics elicited the highest dread of all IBD medications, but this was still lower than their fear of surgery. Patients believed that biologics were of higher benefit than immunomodulators and mesalamines, but riskier. Having the personality trait of an internally developed locus of control was associated with the perception that biologics are less dreadful. CONCLUSIONS: Patients with IBD perceive biologics to be of higher benefit but riskier and more dreadful as compared with immunomodulators. Risk perception may be about more than their knowledge base but also about how much control patients typically believe they have over their daily lives.

Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis patients hospitalized for moderate-severe flares: a phase 2A pilot multi-center, randomized, double-blind, sham-controlled trial.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen delivery. Case series suggest it may have a potential therapeutic benefit in ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an adjunct to steroids for UC flares requiring hospitalization. METHODS: The study was terminated early due to poor recruitment with 18 of the planned 70 patients enrolled. UC patients hospitalized for moderate-severe flares (Mayo score ≥6, endoscopic sub-score ≥2) were block randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study assignment, and assessments were performed by a blinded gastroenterologist. Primary outcome was the clinical remission rate at study day 5 (partial Mayo score ≤2 with no sub-score >1). Key secondary outcomes were: clinical response (reduction in partial Mayo score ≥2, rectal bleeding sub-score of 0-1) and progression to second-line therapy (colectomy or biologic therapy) during the hospitalization. RESULTS: A significantly higher proportion of HBOT-treated patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04). HBOT-treated patients less often required progression to second-line therapy during the hospitalization (10 vs. 63%, p = 0.04). The proportion requiring in-hospital colectomy specifically as second-line therapy for medically refractory UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07). There were no serious adverse events. CONCLUSION: In this small, proof-of-concept, phase 2A trial, the use of HBOT as an adjunctive therapy to steroids for UC patients hospitalized for moderate-severe flares resulted in higher rates of clinical remission, and a reduction in rates of progression to second-line therapy during the hospitalization. Larger well-powered trials are needed, however, to provided definitive evidence of therapeutic benefit.

Delivering High Value Inflammatory Bowel Disease Care Through Telemedicine Visits.

BACKGROUND: Patients with inflammatory bowel disease (IBD) require regular follow-up to manage their care, which requires significant amount of time and out-of-pocket costs. Telemedicine in the form of video virtual visits could serve as an alternative to in-office visits. The aim of this project was to understand if telemedicine can provide high value care (defined as quality/cost) to outpatients with IBD. METHODS: Patients who participated in the IBD telemedicine clinic in the second half of 2015 were included. Patient-reported survey data before and after the virtual visit were collected. A retrospective review was performed on the study cohort for quality outcome measures a year before and after starting the telemedicine clinic. Outcomes were analyzed using simple descriptive statistics. Differences in quality outcomes were compared using odds ratios. RESULTS: Forty-eight patients were included in the analysis. Most patients travel more than 25 miles each way, take half a day off, and on average incur an additional out-of-pocket cost of $62 for an in-office visit. Most patients (98%) agreed that there was enough time spent with their physician, 91% agreed that they felt like the physician understood their disease state, and 78% reported that they clearly understood the follow-up plan after the visit. Analysis of quality outcome measures did not show any drop in the overall quality of care, after initiating the telemedicine program. CONCLUSIONS: Telemedicine offers a low cost and convenient alternative for patients with IBD without compromising quality of care.

Patients with Ulcerative Colitis Are More Concerned About Complications of Their Disease than Side Effects of Medications.

BACKGROUND: Patients with ulcerative colitis (UC) are often fearful about medication side effects and how the disease will affect their future. Our aim was to better understand what aspects of UC, and UC management, are most concerning to patients, and how they would like to be informed about treatment options. METHODS: A Web-based survey was sent to UC patients throughout the United States and Australia. In addition to standard closed-response questions, audio clips were embedded in the survey and respondents showed their strength of agreement or disagreement using moment-to-moment affect-trace methodology. Standard quantitative analysis was used for the survey results, and cluster analysis was performed on the affect-trace responses. RESULTS: A total of 460 patients with UC (370 patients from the United States and 90 patients from Australia) responded to the survey. Of them, 53% of the respondents were women, with a mean age of 49 (range 19-81) years. Most patients (87%) wanted to share treatment decision making with their doctors. The majority, 98%, wanted more than just a basic understanding of their disease. Patients were most concerned about the risk of colorectal cancer (37%), and the possible need for an ileostomy (29%). Only 14% of patients indicated that side effects from medications were their biggest concern. On affect-trace analysis, the most divergence in opinion centered on the appropriate timing for colectomy. CONCLUSIONS: To facilitate informed treatment decisions for UC patients, in addition to reviewing the benefits and risks of medications, it is also important to discuss the best strategies for decreasing the risk of colectomy and colorectal cancer.

Pathogenesis of experimental salmonid alphavirus infection in vivo: an ultrastructural insight.

Salmonid alphavirus (SAV) is an enveloped, single-stranded, positive sense RNA virus belonging to the family Togaviridae. It causes economically devastating disease in cultured salmonids. The characteristic features of SAV infection include severe histopathological changes in the heart, pancreas and skeletal muscles of diseased fish. Although the presence of virus has been reported in a wider range of tissues, the mechanisms responsible for viral tissue tropism and for lesion development during the disease are not clearly described or understood. Previously, we have described membrane-dependent morphogenesis of SAV and associated apoptosis-mediated cell death in vitro. The aims of the present study were to explore ultrastructural changes associated with SAV infection in vivo. Cytolytic changes were observed in heart, but not in gill and head-kidney of virus-infected fish, although they still exhibited signs of SAV morphogenesis. Ultrastructural changes associated with virus replication were also noted in leukocytes in the head kidney of virus-infected fish. These results further describe the presence of degenerative lesions in the heart as expected, but not in the gills and in the kidney.

Using Therapeutic Drug Monitoring to Identify Variable Infliximab Metabolism in an Individual Patient With Ulcerative Colitis.

Biological drugs have significantly improved the quality of life of patients with inflammatory bowel disease. However, after 15 years of using these drugs in practice, we just now are beginning to better understand how to use them most effectively. It has become evident that antitumor necrosis factor agents, such as infliximab, have variable drug clearance across individuals, mostly related to the disease burden at the time of an infusion. In this case report, we demonstrate how therapeutic drug monitoring can be used to personalize a dosing regimen to ensure appropriate induction, and to safely deescalate therapy after remission is achieved. By identifying a change in drug clearance in an individual patient over time, we were able to attain significant cost savings despite the high price of serially measured drug and antibody concentrations.

Risks of serious infection or lymphoma with anti-tumor necrosis factor therapy for pediatric inflammatory bowel disease: a systematic review.

BACKGROUND & AIMS: Many physicians hesitate to recommend anti-tumor necrosis factor (TNF) therapy for pediatric patients with inflammatory bowel disease (IBD) because of concerns about risk of infection and cancer. We performed a systematic review to quantify the incidence of serious infection, lymphoma, and death among pediatric patients with IBD who received anti-TNF therapy. These values were compared with those expected from other treatments, from adults with IBD, and from the general pediatric population. METHODS: We searched MEDLINE, EMBASE, the Cochrane Collaboration, and Web of Knowledge for studies of infliximab therapy for children with ulcerative colitis or Crohn's disease, or adalimumab therapy for children with Crohn's disease. Standardized incidence ratios (SIRs) were calculated, comparing rates of infection and cancer among pediatric patients exposed to anti-TNF agents vs expected rates from pediatric patients not exposed to anti-TNF therapies or adult patients exposed to anti-TNF agents. Our analysis included 5528 patients with 9516 patient-years of follow-up evaluation (PYF). RESULTS: The rate of serious infections among pediatric patients treated with anti-TNF agents (352/10,000 PYF) was similar to that of pediatric patients who received immunomodulator monotherapy (333/10,000 PYF; SIR, 1.06; 95% confidence interval [CI], 0.83-1.36), but significantly lower than the expected rate for pediatric patients treated with steroids (730/10,000 PYF; SIR, 0.48; 95% CI, 0.40-0.58) or adults treated with anti-TNF agents (654/10,000 PYF; SIR, 0.54; 95% CI, 0.43-0.67). Five treatment-related deaths occurred (4 from sepsis and 1 from arrhythmia). Two patients developed lymphoma (2.1/10,000 PYF). This value was similar to the expected rate of lymphoid neoplasia in the entire pediatric population (5.8/100,000 PYF; SIR, 3.5; 95% CI, 0.35-19.6), and lower than the population of pediatric patients receiving thiopurine monotherapy (4.5/10,000 PYF; SIR, 0.47; 95% CI, 0.03-6.44), and among adults treated with anti-TNF agents (6.1/10,000 PYF; SIR, 0.34; 95% CI, 0.04-1.51). CONCLUSIONS: Based on a systematic review, the risk of lymphoma was no greater among children with IBD who received anti-TNF therapy than those treated with other IBD therapies or adults treated with anti-TNF agents. The rate of serious infection was significantly lower among pediatric patients with IBD treated with anti-TNF agents than those treated with steroids, or adults with IBD who received anti-TNF therapy.