关键词： biologic   inflammatory bowel disease   psoriasis   therapy   ustekinumab  

摘要： Ustekinumab (STELARA), a human monoclonal antibody directed against IL-12 and IL-23, is FDA-approved to treat psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. Increasing recognition of paradoxical skin reactions induced by older biologic therapies used for inflammatory bowel diseases (IBD), such as, adalimumab and infliximab, has led to the investigation of ustekinumab for the treatment of the cutaneous and gastrointestinal manifestations of IBD. In addition, ustekinumab may show efficacy in treating paradoxical cutaneous reactions to tumor necrosis factor-alpha (TNF-alpha) inhibitors. A search of the Medline/PubMed database, with additional citations obtained from the references section of relevant articles, yielded 22 articles that were included in this review. Ustekinumab is a safe and effective option for treating the cutaneous manifestations of IBD, such as, metastatic Crohn's disease and pyoderma gangrenosum. It is also an effective treatment for TNF-alpha inhibitor-induced paradoxical skin reactions, such as, psoriasis that do not remit spontaneously or with conventional treatment. Additional studies should focus on the optimal dosing of ustekinumab for dermatologic conditions beyond psoriasis.

关键词： infliximab   therapeutic drug monitoring   cost   inflammatory bowel disease  

摘要： Background Therapeutic drug monitoring (TDM) of infliximab (IFX) levels in inflammatory bowel disease (IBD) patients can help to guide dose adjustments or changes to therapy for selected patients in remission or with secondary loss of response (LOR). Aims To determine how IFX TDM is utilised in a real-life clinical setting and to quantify the potential for TDM to reduce the unnecessary use of IFX. Methods Data from all public IBD IFX level testing performed across Australia were prospectively collected from June 2016 to July 2017 to assess physician-reported for testing indications (induction, in remission or LOR) and associated results. The hypothetical influence of IFX TDM was based on an optimal therapeutic range of 6-10 mg/L for mucosal healing. Results Secondary LOR (reactive TDM) was the most common indication for TDM. These patients have consistently lower median IFX levels: 3.02 mg/L (IQR 1.14-6.67 mg/L) versus 5.22 mg/L (IQR 2.70-8.12 mg/L), P = 0.0001 compared with patients in remission (proactive TDM). TDM helped to identify unnecessary use of IFX in 30.6% of the TDM tests performed in luminal Crohn disease and ulcerative colitis patients, with an associated drug cost saving of $531.38 per IFX TDM test episode. Unnecessary IFX use was identified in 38.9% (96/247) of reactive IFX TDM tests performed and in 19.3% (35/181) of proactive testing. Conclusion Use of both reactive and proactive IFX TDM is cost-effective for IBD management as it informs the clinician where unnecessary use of IFX can be stopped.

摘要： Introduction Inflammatory bowel disease (IBD) frequently requires chronic immunosuppressive treatment and active involvement from patients during treatment decision making. Information about the risk of developing adverse drug reactions (ADRs) to IBD therapies is required in this process. Objective The aim of this study was to describe the ADRs reported in IBD patients from real-world data, using the Dutch nationwide IBDREAM registry, and compare the occurrence and cumulative incidences with the Summary of Product Characteristics (SmPC) of the associated drugs. Methods In this retrospective multicentre study, ADRs related to IBD medication were assessed. Only reports associated with the use of drugs used for the maintenance treatment of IBD were included. All ADRs were verified by healthcare professionals and coded by trained pharmacovigilance assessors. Results In total, 3080 ADRs were reported in 1179 patients. Twenty-three new drug-ADR associations related to the use of azathioprine, mercaptopurine, infliximab, oral mesalamine and thioguanine were reported in the IBDREAM registry that were not mentioned in the corresponding SmPCs. The most frequently reported new association was pyrexia for azathioprine (3.1%) and mercaptopurine (4.9%). In addition, there were seven ADRs with a higher cumulative incidence in IBDREAM compared with the SmPC, and included, among others, arthralgia during mercaptopurine use (2.5%), and diarrhoea (1.4%), alopecia (1.2%) and infections (1.6%) during azathioprine use. Conclusions Based on real-world data, ADR reporting demonstrated new ADRs and higher incidences of ADRs to IBD therapies. This information will contribute to drug safety by updating the SmPCs, allowing better risk assessment and communication towards patients.

关键词： clostridioides difficile   infection   inflammatory bowel disease   ulcerative colitis   crohn's disease   autoimmune disease  

摘要： Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.

关键词： Thiopurine monotherapy   Relapse rates   Inflammatory bowel disease   Side effects  

摘要： Background Immunomodulator monotherapy is an important component in the treatment of inflammatory bowel disease (IBD). However, there is conflicting literature about thiopurines maintaining long-term remission in patients with active IBD. Aim To determine the durable clinical remission rate in adults with Crohn's disease (CD) or ulcerative colitis (UC) on thiopurine monotherapy over 5 years. Methods We performed a retrospective analysis of adult patients identified at McGill University Health Centre from 2009 to 2012. We included IBD patients who initiated thiopurine monotherapy and were in remission for at least 3 months (Harvey-Bradshaw Index (HBI) < 5 points for CD and partial Mayo Score (pMS) < 2 points in UC). The primary endpoint was sustained clinical remission on thiopurines during a 5-year follow-up. This included patients who had not relapsed or discontinued the drug due to side effects. The secondary endpoint was clinical relapse over the follow-up period, which was defined as HBI > 5 in CD and pMS > 2 in UC. Results There were 148 patients included in the study (100 CD;48 UC). At 5 years, 23% (34/148) patients remained in clinical remission on thiopurine monotherapy (25 CD and 9 UC patients). Thirty-three percent (33/100) of CD and 46% (22/48) of UC patients relapsed while on thiopurines. There was no difference in relapse rates between CD and UC patients. Eighty-four percent (42/50) of patients with CD with side effects and all UC (17/17) patients who experienced side effects discontinued the drug. Conclusion This analysis demonstrates that there is poor sustainability of clinical remission in IBD patients on thiopurine monotherapy given that a high proportion of patients discontinue thiopurines due to either relapse or side effects.

关键词： gastrointestinal and hepatic   gastrointestinal disorders   pregnancy loss (abortion   ectopic pregnancy)  

摘要： Aim Inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease (CeD) more commonly affect women of reproductive age. The aim of our study is to evaluate the association between ectopic pregnancy (EP) in women with IBD, IBS, and CeD. Methods We searched MEDLINE, Web of Science, and CINAHL from the database inception date through December 31, 2020. Peer-reviewed publications and abstracts written in English, regarding the association between EP and IBD, IBS, and CeD with controls were included. Quality assessment was conducted based on GRADE criteria. Analyses included odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity between studies was presented with I-2. Results We included five population-based cohort studies. The odds of EP significantly increased in Crohn's disease (CD), but not ulcerative colitis (UC) as compared to IBD-free controls. The odds of EP significantly increased in IBS as compared to women without IBS. No significant difference was observed for odds of EP in women with and without CeD. Conclusions Possible evidence of associations between EP and CD as well as IBS were observed;however, not with UC and CeD. Pregnant women with chronic inflammatory bowel pathologies may warrant cautious monitoring.

关键词： costs   inflammatory bowel disease   outcomes   venous thrombosis  

摘要： Venous thromboembolism (VTE) is a known complication in children with inflammatory bowel disease (IBD). Despite awareness of the increased thrombosis risk in this population, prophylaxis is not standardly used and there is limited published guidance for thrombosis prevention. To better appreciate the impact of thrombosis in this population, we compared children with IBD who did or did not have a VTE, using the Pediatric Health Information System inpatient database from 2009 to 2017. In hospitalized children with IBD, VTE was associated with longer median hospital stays (11 vs 5 days), need for intensive care unit admission (30.2% vs 4.8%), higher median adjusted costs ($32.8k vs $12.3k) and hospital charges ($96.6k vs $36k), and in-hospital death (1.5% vs 0.2%) (P < 0.001 in all comparisons). These findings highlight the need to determine and implement appropriate strategies to reduce VTE rates in children with IBD, given its association with high morbidity, mortality, and cost.

关键词： Chitosan nanoparticle   Melatonin   Inflammatory bowel disease   Ulcerative colitis  

摘要： Inflammatory Bowel Disease (IBD) is a complex inflammatory condition arising due to interactions of environmental and genetic factors that lead to dysregulated immune response and inflammation in intestine. Complementary and alternative medicine approaches have been utilized to treat IBD. However, chronic inflammatory diseases are not medically curable. Hence, potent anti-inflammatory therapeutic agents are urgently warranted. Melatonin has emerged as a potent anti-inflammatory and neuroprotective candidate. Although, it?s therapeutic efficacy is compromised due to less solubility and rapid clearance. Hence, we have synthesized melatonin loaded chitosan nanoparticle (Mel-CSNPs) to improve drug release profile and evaluate its in-vitro and in-vivo therapeutic efficacy. Mel-CSNPs exhibited better anti-inflammatory response in an in-vitro and in-vivo IBD model. Significant anti-inflammatory activity of Mel-CSNPs is attributed to nitric oxide (NO) reduction, inhibited nuclear translocation of NF-kB p65 and reduced IL-1 beta and IL-6 expression. In-vivo biodistribution study has shown a good distribution profile. Effective in-vivo therapeutic efficiency of Mel-CSNPs has been confirmed with reduced disease activity index parameters and inhibited neutrophilic infiltration. Histological evaluation has further proved the protective effect of Mel-CSNPs by preventing crypt damage and immune cells infiltration against Dextran Sodium Sulphate induced insults. Immuno-histochemical analysis has confirmed anti-inflammatory action of Mel-CSNPs with reduction of inflammatory markers, Nitric Oxide Synthase-2 (NOS2) and Nitrotyrosine. Indeed, this study divulges anti-inflammatory activity of Mel-CSNPs by improving the therapeutic potential of melatonin.