Inflammatory Bowel Disease Therapy Research Articles

Eosinophilic Esophagitis and Inflammatory Bowel Disease: What Are the Differences?

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are chronic inflammatory disorders of the gastrointestinal tract, with EoE predominantly provoked by food and aeroallergens, whereas IBD is driven by a broader spectrum of immunopathological and environmental triggers. This review presents a comprehensive comparison of the pathophysiological and therapeutic strategies for EoE and IBD. We examine the current understanding of their underlying mechanisms, particularly the interplay between environmental factors and genetic susceptibility. A crucial element in both diseases is the integrity of the epithelial barrier, whose disruption plays a central role in their pathogenesis. The involvement of eosinophils, mast cells, B cells, T cells, dendritic cells, macrophages, and their associated cytokines is examined, highlighting the importance of targeting cytokine signaling pathways to modulate immune-epithelial interactions. We propose that advances in computation tools will uncover the significance of G-protein coupled receptors (GPCRs) in connecting immune and epithelial cells, leading to novel therapies for EoE and IBD.

Risks and benefits of anti-TNF therapy for ulcerative colitis in a patient with autoimmune hepatitis-related cirrhosis: Case report.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by continuous inflammation of the colonic mucosa. Autoimmune hepatitis (AIH) is a chronic liver disease characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis, and favorable response to immunosuppression. An association between IBD and AIH is uncommon, and experts have suggested that in patients with overlapping IBD and AIH, the anti-tumor necrosis factor agents can be used. Therefore, this study reports a rare case of a patient with liver cirrhosis due to AIH and UC refractory to conventional treatment and discusses the risks and benefits of using anti-tumor necrosis factor in both conditions. A 28-year-old female presented with symptoms of diarrhea, abdominal pain, asthenia, and inappetence, accompanied by abdominal collateral circulation, anemia, alteration of liver enzymes, and elevation of C-reactive protein levels. The patient underwent a liver biopsy, which was consistent with liver cirrhosis due to AIH. Colonoscopy showed an inflammatory process throughout the colon, compatible with moderately active UC. The patient received mesalazine, azathioprine, and corticotherapy, with no control of the inflammatory process. Faced with refractoriness to drug treatment and side effects of corticosteroids with an increased risk of severe infection due to cirrhosis, we opted to use infliximab for the treatment of UC. The patient presented with a clinical response and infliximab therapy was maintained. Eight months after starting infliximab therapy, the patient developed pneumonia with complications from disseminated intravascular coagulation and died. AIH is a rare cause of elevated transaminase levels in patients with UC. The best treatment to control the 2 conditions should be evaluated with vigilance for the side effects of medications, mainly infections, especially in patients with cirrhosis.

Factors Associated with Delays in Initiating Biologic Therapy in Patients with Inflammatory Bowel Disease.

Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables. To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay. This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication. In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12-37] days (infliximab, 19 [13-33] days; adalimumab, 10 [5-26] days; vedolizumab, 21 [14-42] days; and ustekinumab, 21 [14-42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval. There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval.

De-escalating therapy in inflammatory bowel disease: Results from an observational study in clinical practice

Background and objectivesCombination therapy with an immunomodulator (IMM) and an anti-TNF is commonly recommended in Crohn's disease (CD) and ulcerative colitis (UC) patients. However, little is known about relapse rates after therapeutic de-escalation. This study aimed to evaluate the risk of relapse in a cohort of UC and CD patients with long-standing clinical remission after discontinuation of IMM or anti-TNF and to identify predictive factors for relapse. MethodsThis retrospective study included patients with UC or CD on combination therapy and clinical remission for at least 6 months. IMM or anti-TNF was stopped upon physician decision. Primary objective was to evaluate the relapse rates after discontinuation of IMM or anti-TNF and to analyze predictors of relapse. ResultsThe study included 88 patients, 48 patients (54.5%) discontinued IMM and 40 (45.5%) anti-TNF. During follow-up, relapse rates were 16.7% and 52.5% in the IMM discontinuation group and anti-TNF discontinuation group, respectively (p<0.001). Multivariate analysis showed that anti-TNF discontinuation (HR=3.01; 95% CI=1.22–7.43) and ileal CD location (HR=2.36; 95% CI=1.02–5.47) were predictive factors for relapse while inflammatory CD phenotype was a protective factor (HR=0.32; 95% CI=0.11–0.90). Reintroduction of anti-TNF upon relapse was effective and safe. ConclusionAnti-TNF discontinuation led to significantly higher relapse rates compared to IMM discontinuation in UC and CD patients on combination therapy. Anti-TNF discontinuation and ileal CD location were identified as predictive factors for relapse while inflammatory CD phenotype was a protective factor. Retreatment after anti-TNF discontinuation was effective and safe.

Recent advances in measuring the effects of diet on gastrointestinal physiology: Sniffing luminal gases and fecal volatile organic compounds.

Despite the huge pool of ideas on how diet can be manipulated to ameliorate or prevent illnesses, our understanding of how specific changes in diet influence the gastrointestinal tract is limited. This review aims to describe two innovative investigative techniques that are helping lift the veil of mystery about the workings of the gut. First, the gas-sensing capsule is a telemetric swallowable device that provides unique information on gastric physiology, small intestinal microbial activity, and fermentative patterns in the colon. Its ability to accurately measure regional and whole-gut transit times in ambulant humans has been confirmed. Luminal concentrations of hydrogen and carbon dioxide are measured by sampling through the gastrointestinal tract, and such application has enabled mapping of the relative amounts of fermentation of carbohydrates in proximal-versus-distal colon after manipulation of the types and amounts of dietary fiber. Second, changes in the smell of feces, via analysis of volatile organic compounds, occur in response to the diet, and by the presence and therapy of irritable bowel syndrome and inflammatory bowel disease. Such information is likely to aid our understanding of what dietary change can do to the colonic luminal microenvironment, and may value-add to diagnosis and therapeutic design. In conclusion, such methodologies enable a more complete physiological profile of the gastrointestinal tract to be created. Systematic description in various cohorts and effects of dietary interventions, particularly when co-ordinated with the analysis of microbiome, are needed.

Korean Red Ginseng alleviates dextran sodium sulfate-induced colitis through gut microbiota modulation in mice

BackgroundThere is a growing interest in understanding the association between the gut microbiota and inflammatory bowel disease (IBD). Natural compounds, such as Korean Red Ginseng (KRG), show promise for IBD treatment because of their ability to influence gut microbiota. This study explored the effects of KRG on gut microbiota modulation and subsequent intestinal epithelial cell regeneration in an experimental colitis model. MethodUsing a mouse model of colitis induced by 2 % dextran sodium sulfate, the study administered 200 or 400 mg/kg/day of KRG to evaluate its biological effects. Colitis symptoms were assessed through body weight, disease activity index, colon length, and histological analysis. The microbial composition in the fecal was determined using 16S rRNA sequencing. To evaluate regeneration signals in the colon, western blotting and immunohistochemistry assays were conducted. ResultAdministration of KRG effectively mitigated colitis symptoms in mice, as indicated by histological examination showing alleviated epithelial damage and inflammation, along with increased mucus production. Microbiota analysis showed that KRG significantly altered microbial diversity, favoring beneficial taxa and suppressing harmful taxa. Moreover, ameliorated β-catenin/transcription factor-4 protein expression, a key signal associated with epithelial cell regeneration, was observed in the KRG treated groups, accompanied by improved intestinal linings. ConclusionThese findings suggest that KRG exerts biological effects in colitis by modulating gut microbiota and creating a favorable intestinal environment, thereby reducing regenerative signals. Further research is warranted to elucidate the cellular and molecular mechanisms underlying the interaction of KRG with gut microbiota and pave the way for effective IBD therapies.

Toxicity and therapeutic property of dioxopiperidin derivative SKT40 demonstrated in-vivo zebrafish model due to inflammatory bowel disease

Inflammatory bowel disease (IBD) encompasses chronic disorders that cause severe inflammation in the digestive tract. This study evaluates (E)-3-(3,4-dichlorophenyl)-N-(2,6-dioxopiperidin-3-yl) acrylamide (named SKT40), a derivative of dioxopiperidinamide, as a potential novel treatment for IBD. The pharmacological activity of SKT40 indicated positive interactions using network pharmacology and molecular docking in silico. In vivo, adult and larval zebrafish were tested to evaluate the effectiveness of SKT40 at different concentrations (7.5 μM, 10 μM, 15 μM) in preventing dextran sulfate sodium (DSS)-induced intestinal inflammation. The administration of SKT40 resulted in positive effects by reducing reactive oxygen species (ROS), lipid peroxidation, and cell apoptosis in zebrafish larvae. SKT40 demonstrated a significant reduction in intestinal damage in adult zebrafish by increasing antioxidant enzymes that combat the causes of IBD, such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). It also reduces cellular damage and inflammation, as indicated by decreased levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA). Gene expression analysis identified downregulation in gene expression of inflammatory mediators such as TNF-α, IL-1β, COX-2, and IL-6. Histopathological analysis showed tissue repair from DSS-induced damage and indicated reduced hyperplasia of goblet cells. These findings suggest that SKT40 effectively treats intestinal damage, highlighting its potential as a promising candidate for IBD therapy.

Therapeutic role of extracellular vesicles from human umbilical cord mesenchymal stem cells and their wide therapeutic implications in inflammatory bowel disease and other inflammatory disorder.

The chronic immune-mediated inflammatory condition known as inflammatory bowel disease (IBD) significantly affects the gastrointestinal system. While the precise etiology of IBD remains elusive, extensive research suggests that a range of pathophysiological pathways and immunopathological mechanisms may significantly contribute as potential factors. Mesenchymal stem cells (MSCs) have shown significant potential in the development of novel therapeutic approaches for various medical conditions. However, some MSCs have been found to exhibit tumorigenic characteristics, which limit their potential for medical treatments. The extracellular vesicles (EVs), paracrine factors play a crucial role in the therapeutic benefits conferred by MSCs. The EVs consist of proteins, microRNAs, and lipids, and are instrumental in facilitating intercellular communication. Due to the ease of maintenance, and decreased immunogenicity, tumorigenicity the EVs have become a new and exciting option for whole cell treatment. This review comprehensively assesses recent preclinical research on human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs as a potential IBD therapy. It comprehensively addresses key aspects of various conditions, including diabetes, cancer, dermal injuries, neurological disorders, cardiovascular issues, liver and kidney diseases, and bone-related afflictions.

Efficacy and safety of fecal microbiota transplantation for treatment of ulcerative colitis: A post-consensus systematic review and meta-analysis.

Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary. To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis. The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively. We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups. FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy.

Enzyme/ROS dual-sensitive nanoplatform with on-demand Celastrol release capacity for enhanced ulcerative colitis therapy by ROS scavenging, microbiota rebalancing, inflammation alleviating

BackgroundThe oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release.MethodsA multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC.ResultsOwing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome.ConclusionsWe provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand.Graphical

Hydroalcoholic extract of Araucaria sp. brown propolis alleviates ulcerative colitis induced by TNBS in rats by reducing inflammatory cell infiltration and oxidative damage.

To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded. HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo. HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.

Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis

A monoclonal antibody called mirikizumab is used to treat ulcerative colitis. It is marketed under the Omvoh brand. It is intended to bind to interleukin-23 (IL-23) and obstruct its function. Upper respiratory tract (nose and throat) infections, headaches, rashes, and injection site responses (when administered by subcutaneous injection) are the most frequent adverse effects. In the United States in October 2023 and the European Union in May 2023, mirikizumab was authorized for medicinal use. For the treatment of people with moderately to highly active ulcerative colitis who have not responded well to, have lost responsiveness to, or are intolerant to either biologic therapy or conventional therapy, mirikizumab is suggested. A subset of people with ulcerative colitis (UC) do not react to currently available medications, despite advancements in UC medical therapy. Many innovative medications have recently acquired regulatory approval for use in UC, or are in the latter stages of development. The novel antibody mirikizumab, which is given intravenously (IV), binds to the inflammatory protein interleukin 23 and inhibits its function, preventing inflammation from being triggered. For individuals with moderately to highly active UC, mirikizumab would therefore provide an additional therapy choice if legalized.

More on the interplay between gut microbiota, autophagy, and inflammatory bowel disease is needed.

The concept of inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, represents a complex and growing global health concern resulting from a multifactorial etiology. Both dysfunctional autophagy and dysbiosis contribute to IBD, with their combined effects exacerbating the related inflammatory condition. As a result, the existing interconnection between gut microbiota, autophagy, and the host's immune system is a decisive factor in the occurrence of IBD. The factors that influence the gut microbiota and their impact are another important point in this regard. Based on this initial perspective, this manuscript briefly highlighted the intricate interplay between the gut microbiota, autophagy, and IBD pathogenesis. In addition, it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context. Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms, which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.

Saffron as a Promising Therapy for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the gastrointestinal tract (GI), characterized by recurrent episodes of inflammation and tissue destruction. It affects an increasing number of individuals worldwide who suffer from Crohn's disease (CD) or ulcerative colitis (UC). Despite substantial advances in understanding the underlying causes of IBD, the available treatments remain restricted and are sometimes accompanied by severe consequences. Consequently, there is an urgent need to study alternate therapeutic options. This review assesses the present drugs, identifies their limitations, and proposes the use of saffron, a natural plant with great therapeutic potential based on preclinical and clinical investigations. Saffron has gained attention for its potential therapeutic benefits in treating various ailments due to its established bioactive compounds possessing antioxidant and anti-inflammatory properties. This review covers how saffron impacts the levels of calprotectin, an inflammatory marker, for various inflammatory responses in multiple diseases including IBD. Data from clinical trials were assessed to determine the efficacy and safety of using saffron to counter inflammation in multiple diseases. Studies have shown that saffron may protect against inflammatory bowel disease (IBD) through several mechanisms by inhibiting pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), reducing oxidative stress through antioxidant effects, enhancing mucosal barrier function by upregulating tight junction proteins, and modulating the gut microbiota composition to promote beneficial bacteria while suppressing pathogenic ones; these combined actions contribute to its therapeutic potential in managing and alleviating the symptoms of IBD. This will enable future research endeavors and expedite the translation of saffron-based interventions into clinical practice as a valuable adjunctive therapy or a potential alternative to conventional treatments, thereby enhancing the quality of life for individuals suffering from inflammatory diseases including IBD.

ROS-responsive thioketal nanoparticles delivering system for targeted ulcerative colitis therapy with potent HDAC6 inhibitor, tubastatin A

Ulcerative colitis (UC) is a common gastrointestinal problem characterized by the mucosal injury primarily affecting the large intestine. Currently available therapies are not satisfactory as evidenced by high relapse rate and adverse effects. In this study we aimed to develop an effective drug delivery system using reactive oxygen species (ROS)-responsive thioketal nanoparticles (TKNP), to deliver tubastatin A, a potent HDAC6 inhibitor, to the inflamed colon in mice with ulcerative colitis (UC). TKNPs were synthesized by step-growth polymerization from an acetal exchange reaction while TUBA-TKNP was prepared using the single emulsion solvent evaporation technique. Our developed nanoparticle showed release of tubastatin A only in presence of ROS which is found to be highly present at the site of inflamed colon. Oral administration of TUBA-TKNP resulted in the higher accumulation of tubastatin A at the inflamed colon site and decreased the inflammation as evidenced by reduced infiltration of immune cells and decreased level of pro-inflammatory cytokines in TUBA-TKNP treated mice. In summary, our results show the successful localization of tubastatin A at the site of colon inflammation through TUBA-TKNP delivery, as well as resolution of clinical features of UC in mice.

A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease.

Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM's effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase. We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect. Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient's final time point matched the observed effects in 9 of the 11 patients. This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.

Postbiotics in inflammatory bowel disease: efficacy, mechanism, and therapeutic implications.

Inflammatory bowel disease (IBD) is one of the most challenging diseases in the 21st century, and more than 10 million people around the world suffer from IBD. Because of the limitations and adverse effects associated with conventional IBD therapies, there has been increased scientific interest in microbial-derived biomolecules, known as postbiotics. Postbiotics are defined as the preparation of inanimate microorganisms and/or their components that confer a health benefit on the host, comprising inactivated microbial cells, cell fractions, metabolites, etc. Postbiotics have shown potential in enhancing IBD treatment by reducing inflammation, modulating the immune system, stabilizing intestinal flora and maintaining the integrity of intestinal barriers. Consequently, they are considered promising adjunctive therapies for IBD. Recent studies indicate that postbiotics offer distinctive advantages, including spanning clinical (safe origin), technological (easy for storage and transportation) and economic (reduced production costs) dimensions, rendering them suitable for widespread applications in functional food/pharmaceutical. This review offers a comprehensive overview of the definition, classification and applications of postbiotics, with an emphasis on their biological activity in both the prevention and treatment of IBD. © 2024 Society of Chemical Industry.

Combining Gut Microbiota Modulation and Enzymatic-Triggered Colonic Delivery by Prebiotic Nanoparticles Improves Mouse Colitis Therapy.

The efficacy of ulcerative colitis (UC) therapy is closely connected to the composition of gut microbiota in the gastrointestinal tract. Prebiotic-based nanoparticles (NPs) provide a more precise approach to alleviate UC via modulating gut microbiota dysbiosis. The present study develops an efficient prebiotic-based colon-targeted drug delivery system (PCDDS) by using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a prebiotic shell, with the anti-inflammatory drug sulfasalazine (SAS) loaded into a poly(lactic-co-glycolic acid) (PLGA) core to construct SAS@PLGA-Csn-Pcn NPs. Then, we examine its characterization, cellular uptake, and invivo therapeutic efficacy. The results of our study indicate that the Pcn/Csn shell confers efficient pH-sensitivity properties. The gut microbiota-secreted pectinase serves as the trigger agent for Pcn/Csn shell degradation, and the resulting Pcn oligosaccharides possess a substantial prebiotic property. Meanwhile, the formed PCDDSs exhibit robust biodistribution and accumulation in the colon tissue, rapid cellular uptake, efficient invivo therapeutic efficacy, and modulation of gut microbiota dysbiosis in a mouse colitis model. Collectively, our synthetic PCDDSs demonstrate a promising and synergistic strategy for UC therapy.

Rescue Therapies for Steroid-Refractory Acute Severe Ulcerative Colitis: A Systemic Review and Network Meta-analysis.

Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis (steroid-refractory (SR) ASUC) requires colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC. Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo. Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates. This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.

Back to the drawing board: Overview of the next generation of combination therapy for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is entering a potentially new era of combined therapeutics. Triantafillidis et al provide an insightful review of the current state of combination therapy, with a focus on the use of a combined biologic and immunomodulator, as well as emerging data on the future potential of dual-biologic therapy (DBT). While current evidence for DBT is limited, encouraging safety profiles and ongoing trials suggest a brighter future for this approach. The importance of controlled trials should be stressed in establishing new treatment paradigms. Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.