Optimizing the Use of Current Treatments and Emerging Therapeutic Approaches to Achieve Therapeutic Success in Patients with Inflammatory Bowel Disease

Nakase, Hiroshi

doi:10.5009/gnl18203

Cited by 25 publications

(19 citation statements)

References 78 publications

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“…Over the last couple of years, a number of new drugs have been developed and approved based either on inhibition of immune cell trafficking or on inhibition of cytokine signaling [19][20][21][22]. Vedolizumab, a monoclonal antibody directed against α4β7 integrin, has been approved for the treatment of patients with moderate-to-severe UC or CD who have inadequate response, loss of response or intolerance to conventional therapy with corticosteroids, immunosuppressives, or anti-TNF therapy.…”

Section: Medical Therapy For CDmentioning

confidence: 99%

Treatment Algorithms for Crohn’s Disease

Sulz

Burri

Michetti³

et al. 2020

Digestion

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Background: Treatment of Crohn's disease (CD) patients is complex as therapy choices depend on a variety of factors, such as location and severity of inflammation, disease behavior (inflammatory, stricturing or penetrating) but also comorbidities, extra-intestinal manifestations, the patient's age, and previous therapies. Subsequently, the choice of treatment should be tailored to the individual patient. Summary: This article gives the reader therapy algorithms as a guide through different CD scenarios to support the physician's decision making. New compounds introduced in CD therapy in recent years justify such an update on standard approaches. Ustekinumab and vedolizumab and their positions within the treatment options are discussed. Fistulizing perianal disease and postoperative medical prophylaxis are depicted in separate chapters with own algorithms. Key Messages: In recent years, a variety of new drugs became available to treat patients with CD-especially those who are antitumor necrosis factor (TNF) experienced with ongoing inflammation. The definitive role of vedolizumab and ustekinumab is not yet fully clarified. However, with the advantage of good safety profiles over TNF-inhibitors, these drugs will be more frequently used in the near future, also as first-line biologicals, compared to TNF-inhibitors. Concerning treatment of fistulizing disease, the knowledge of the exact anatomy of the fistula is of major importance. An interdisciplinary discussion involving gastroenterologists, surgeons, and in some cases gynecologists may help to optimize the treatment plan. Regarding the postsurgical setting in CD patients, according to the very recent Cochrane Network meta-analysis, mesalazine should be at least positioned equivalent to thiopurines and TNF-inhibitors, as shown in our algorithm.

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Section: Medical Therapy For CDmentioning

confidence: 99%

Treatment Algorithms for Crohn’s Disease

Sulz

Burri

Michetti³

et al. 2020

Digestion

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“…Interestingly, it has been reported that TAC has an effect on macrophages as well as T cells and suppresses the production of IL-12 and TNF-A depending on the dose-escalation [37]. Generally, we consider administering either cyclosporine A (CsA) or TAC to patients with severely active UC, particularly steroid-refractory cases [38].…”

Section: Ibd Treatment From the Perspective Of The Adaptive Immune Symentioning

confidence: 99%

“…Now, we objectively evaluate the disease activity of IBD with endoscopic findings, biomarkers, etc. With these changes in the evaluation of disease activity, the 'treat to target (T2T)' strategy, which uses objective clinical and biochemical outcome measures to assist clinicians in making decisions related to therapy modification, has spread in the IBD field as well as rheumatology field [38].…”

Section: What Has Changed In the Clinical Ibd Field Since The Emergenmentioning

confidence: 99%

Treatment of inflammatory bowel disease from the immunological perspective

Nakase

2020

Immunological Medicine

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Since 1950, the number of patients with inflammatory bowel disease (IBD) in Japan has been increasing. Recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development based on basic research data. In particular, the emergence of biologics has brought about a paradigm shift in the treatment of IBD. However, there are still IBD patients who are refractory to these biologics. IBD pathophysiology is extremely complex. Therefore, to address these clinical issues, further clinical and basic data are required. The bottom line of IBD drug therapy is still to use the most of recent treatments. Therefore, the physicians should be familiar with the modes of action (MOA) of the available drugs.

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“…In addition to these experimental concepts, several current IBD treatments were shown to have a protective or regenerative effect on the damaged epithelium and to promote MH [reviewed in (154)]. Aminosalicylates not only affect intestinal inflammation via various signaling pathways such as NF-κB, but also directly stimulate epithelial wound healing by enhancing epithelial cell restitution and proliferation (155)(156)(157). Anti-TNF-α antibodies such as infliximab and adalimumab are able to induce and maintain MH (144,(158)(159)(160) by restricting the inflammatory infiltrate and T cell proliferation within the lamina propria and by downregulating the expression of metalloproteinases and pro-inflammatory molecules (161).…”

Section: Clinical Relevance Of Mucosal Healing and Therapeutic Approamentioning

confidence: 99%

Intestinal Mucosal Wound Healing and Barrier Integrity in IBD–Crosstalk and Trafficking of Cellular Players

et al. 2021

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The intestinal epithelial barrier is carrying out two major functions: restricting the entry of potentially harmful substances while on the other hand allowing the selective passage of nutrients. Thus, an intact epithelial barrier is vital to preserve the integrity of the host and to prevent development of disease. Vice versa, an impaired intestinal epithelial barrier function is a hallmark in the development and perpetuation of inflammatory bowel disease (IBD). Besides a multitude of genetic, molecular and cellular alterations predisposing for or driving barrier dysintegrity in IBD, the appearance of intestinal mucosal wounds is a characteristic event of intestinal inflammation apparently inducing breakdown of the intestinal epithelial barrier. Upon injury, the intestinal mucosa undergoes a wound healing process counteracting this breakdown, which is controlled by complex mechanisms such as epithelial restitution, proliferation and differentiation, but also immune cells like macrophages, granulocytes and lymphocytes. Consequently, the repair of mucosal wounds is dependent on a series of events including coordinated trafficking of immune cells to dedicated sites and complex interactions among the cellular players and other mediators involved. Therefore, a better understanding of the crosstalk between epithelial and immune cells as well as cell trafficking during intestinal wound repair is necessary for the development of improved future therapies. In this review, we summarize current concepts on intestinal mucosal wound healing introducing the main cellular mediators and their interplay as well as their trafficking characteristics, before finally discussing the clinical relevance and translational approaches to therapeutically target this process in a clinical setting.

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Optimizing the Use of Current Treatments and Emerging Therapeutic Approaches to Achieve Therapeutic Success in Patients with Inflammatory Bowel Disease

Cited by 25 publications

References 78 publications

Treatment Algorithms for Crohn’s Disease

Treatment Algorithms for Crohn’s Disease

Treatment of inflammatory bowel disease from the immunological perspective

Intestinal Mucosal Wound Healing and Barrier Integrity in IBD–Crosstalk and Trafficking of Cellular Players

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