Risks and benefits of combining immunosuppressives and biological agents in inflammatory bowel disease: is the synergy worth the risk?
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ABSTRACT:
SUBMITTER: Hanauer SB
PROVIDER: S-EPMC1954967 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Inflammatory Bowel Disease (IBD) comprises a group of disorders, in particular Crohn's disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation affecting the gastrointestinal tract. The treatment of these conditions is primarily based on anti-inflammatory drugs, although the use of biological drugs with lower side effects quickly increased in the last decade. However, the presence of certain polymorphisms in the population may determine a different outcome in response to therapy, reflecting the heterogeneity of the efficacy in patients. Considering that several studies showed important correlations between genetic polymorphisms and response to biological treatments in IBD patients, this systematic review aims to summarize the pharmacogenetics of biologicals approved for IBD, thus highlighting a possible association between some polymorphisms and drug response. With this purpose, we reviewed PubMed papers published over the past 21 years (2000-2021), using as the search term "drug name and IBD or CD or UC and polymorphisms" to underline the role of pharmacogenetic tests in approaching the disease with a targeted therapy.
| S-EPMC8699014 | biostudies-literature
Project description:Psoriasis and the spectrum of inflammatory bowel diseases (IBD) are chronic, inflammatory, organotropic conditions. The epidemiologic coexistence of these diseases is corroborated by findings at the level of disease, biogeography, and intrafamilial and intrapatient coincidence. The identification of shared susceptibility loci and DNA polymorphisms has confirmed this correlation at a genetic level. The pathogenesis of both diseases implicates the innate and adaptive segments of the immune system. Increased permeability of the epidermal barrier in skin and intestine underlies the augmented interaction of allergens and pathogens with inflammatory receptors of immune cells. The immune response between psoriasis and IBD is similar and comprises phagocytic, dendritic, and natural killer cell, along with a milieu of cytokines and antimicrobial peptides that stimulate T-cells. The interplay between dendritic cells and Th17 cells appears to be the core dysregulated immune pathway in all these conditions. The distinct similarities in the pathogenesis are also reflected in the wide overlapping of their therapeutic approaches. Small-molecule pharmacologic immunomodulators have been applied, and more recently, biologic treatments that target proinflammatory interleukins have been introduced or are currently being evaluated. However, the fact that some treatments are quite selective for either skin or gut conditions also highlights their crucial pathophysiologic differences. In the present review, a comprehensive comparison of risk factors, pathogenesis links, and therapeutic strategies for psoriasis and IBD is presented. Specific emphasis is placed on the role of the immune cell species and inflammatory mediators participating in the pathogenesis of these diseases.
| S-EPMC5683131 | biostudies-literature
Project description:The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. To evaluate the impact of biologics on the risk of PC. A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.
| S-EPMC8509475 | biostudies-literature
Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs) are often coadministered with proton-pump inhibitors (PPIs) to reduce NSAID-induced gastrointestinal (GI) adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs.
| S-EPMC5817415 | biostudies-other
Project description:BACKGROUND:Treatment with biological agents such as anti-tumor necrosis factors (TNFs) has become standard of care in moderate to severe pediatric inflammatory bowel disease (IBD). However, a significant proportion of patients experience loss of response to anti-TNFs, need treatment escalation, or develop side effects. There is no data in the literature regarding combination of biological agents in pediatric IBD. METHODS:At our hospital, which is a tertiary referral center, we have combined the anti-TNF infliximab with either vedolizumab or ustekinumab in patients with severe pediatric IBD. The indications for dual biological therapy were insufficient efficacy of infliximab or vedolizumab monotherapy, or side effects such as psoriasis due to anti-TNFs. RESULTS:Eight patients (four boys) aged 14-17.5 years received a combination of infliximab and vedolizumab due to only a partial response to infliximab, four with Crohn's disease (CD) and four with ulcerative colitis (UC). Clinical remission was achieved in four patients (3 UC) and four had a colectomy (3 CD, 1 UC). Five CD patients (3 girls) aged 11-17 years, on maintenance therapy with infliximab, developed psoriasis resistant to topical treatment. A combination of infliximab and ustekinumab resulted in clinical remission of CD without skin symptoms. No serious adverse events occurred in any of the patients on combination therapy. Thirteen publications report on combining biologicals, all in adult IBD. CONCLUSION:In pediatric IBD, combining biological agents seems to be safe and beneficial in selected patients. The safety should be addressed in long-term follow-up studies.
| S-EPMC7383034 | biostudies-literature
Project description:The cumulative impact of chronic inflammation in patients with inflammatory bowel diseases predisposes to the development of inflammatory bowel disease-associated colorectal cancer [IBD-CRC]. Inflammation can induce mutagenesis, and the relapsing-remitting nature of this inflammation, together with epithelial regeneration, may exert selective pressure accelerating carcinogenesis. The molecular pathogenesis of IBD-CRC, termed the 'inflammation-dysplasia-carcinoma' sequence, is well described. However, the immunopathogenesis of IBD-CRC is less well understood. The impact of novel immunosuppressive therapies, which aim to achieve deep remission, is mostly unknown. Therefore, this timely review summarizes the clinical context of IBD-CRC, outlines the molecular and immunological basis of disease pathogenesis, and considers the impact of novel biological therapies.
| S-EPMC8684457 | biostudies-literature
Project description:BACKGROUND:Malnutrition is common in inflammatory bowel disease (IBD), requiring timely and sufficient nutritional supplementation. In patients hospitalized for active disease, symptoms and/or altered intestinal function hinder enteral nutrition feasibility. In this scenario, parenteral nutrition (PN) is used. We aimed (1) to assess the frequency of PN use between 1997 and 2012 among hospitalized pediatric patients with IBD, (2) to determine the risk of in-hospital thrombus and infection associated with PN, and (3) to identify predictors of thrombus and infection in pediatric IBD hospitalizations utilizing PN. METHODS:We performed a cross-sectional analysis of pediatric patients hospitalized between 1997 and 2012. We used the Kids' Inpatient Database (KID) to identify pediatric patients (?18 years of age) with Crohn's disease (CD) or ulcerative colitis (UC), PN exposure, and primary outcomes including thrombus and infection. We used multivariable regression to identify risk factors for outcomes of interest. RESULTS:Parenteral nutrition was utilized in 3732 (12%) of 30,914 IBD hospitalizations. Three percent of PN patients experienced a thrombotic complication, and 5.5% experienced an infectious complication. Multivariate analysis showed PN as an independent risk factor for thrombus (odds ratio [OR], 4.3; 95% confidence interval [CI], 3.2-5.6) and infection (OR, 3.8; 95% CI, 3.1-4.6). Surgery was an independent risk factor for thrombus (OR, 2.0; 95% CI, 1.4-2.7) and infection (OR, 2.5; 95% CI, 2.0-3.1) in hospitalizations exposed to PN. CONCLUSIONS:Hospitalized pediatric IBD patients, particularly surgical, receiving PN are at increased risk for thrombosis and infection. Clinicians must balance these risks with the benefits of PN.
| S-EPMC6383858 | biostudies-literature
Project description:Patients with inflammatory bowel disease are commonly treated with immunomodulators and biologic therapy. These treatments can be very effective, but are associated with risks of adverse events that need to be discussed with patients. Effectively communicating risks of therapy can be challenging based on time constraints, misinformation available on the Internet and from others, and the lack of tools to efficiently share accurate data with patients and their families. Providers need to acknowledge the emotional aspect involved in the perception of risk, and be aware of mistakes that can easily be made in communicating with patients. Tools are available to make medical data easier to understand, and these techniques have been adapted for patients with inflammatory bowel disease. By more clearly communicating with patients, we can ensure that they are making informed medical decisions that fit with their personal preferences for treatment.
| S-EPMC3037287 | biostudies-literature
Project description:IntroductionFecal lactoferrin (FL) is a timely and accurate marker of inflammation in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to verify whether FL can predict primary nonresponse (PNR) to biologic agents during induction.MethodsRetrospective outcome review in 27 patients (13 with CD and 14 with UC) tested for baseline FL and retested within a week after the first and second induction doses. Clinical/biochemical outcomes were evaluated at end of induction and at follow-up (3-24 months).ResultsCompared to baseline, changes of the Harvey-Bradshaw (CD) and Partial Mayo Scoring (UC) indices at end of induction separated responders (18/27 or 67%) from nonresponders (9/17 or 33%). In all patients, the initial FL value at induction decreased compared to baseline, continuing to decrease after the following dose in clinical responders while bouncing back in the others. Models targeting the 2 consecutively decreased FL values or the second FL value compared to baseline or the second FL value compared to the first were able to accurately predict response at end of induction. Follow-up assessment confirmed clinical remission in initial responders (with FL values reduced on the average by 94 ± 10% compared to baseline).ConclusionsIn CD and UC patients during induction with biologic agents, early FL measurements accurately separate clinical responders from those experiencing PNR. The method described here offers several potential advantages over other strategies to assess and manage these patients.
| S-EPMC8686729 | biostudies-literature
Project description:OBJECTIVES:To explore the trends and the predictors of incident malignant cancer among patients with inflammatory bowel disease [IBD]. METHODS:We identified a cohort of all patients with incident IBD in Quebec, Canada, from 1998 to 2015, using provincial administrative health-care databases [RAMQ and Med-Echo]. Annual incidence rates [IRs] of cancer were calculated using Poisson regression and were compared with those of the Quebec population using standardized incidence ratios [SIRs ]. Temporal trends in these rates were evaluated by fitting generalized linear models. Conditional logistic regression was used to estimate odds ratios [ORs] for predictors associated with cancer development. RESULTS:The cohort included 35?985 patients with IBD, of which 2275 developed cancers over a mean follow-up of 8 years (IR 785.6 per 100?000 persons per year; 95% confidence interval [CI] 754.0-818.5). The rate of colorectal cancer decreased significantly from 1998 to 2015 [p < 0.05 for linear trend], but the incidence remained higher than expected, compared with the Quebec population [SIR 1.39; 95% CI 1.19-1.60]. Rates of extraintestinal cancers increased non-significantly over time [p = 0.11 for linear trend]. In the IBD cohort, chronic kidney disease [OR 1.29; 95% CI 1.17-1.43], respiratory diseases [OR 1.07; 95% CI 1.02-1.12], and diabetes mellitus [OR 1.06; 95% CI 1.01-1.11] were associated with an increase in the incidence of cancer. CONCLUSIONS:The decreasing rates of colorectal cancer suggest improved management and care in IBD. Further studies are needed to explore the impact of comorbid conditions on the risk of cancer in IBD.
| S-EPMC6764102 | biostudies-literature