P.08.19 PREVALENCE OF STEROID DEPENDENCE AND RESISTANCE IN INFLAMMATORY BOWEL DISEASE PATIENTS: TREATMENT OPTIONS AS STEROID-SPARING AGENTS IN A SINGLE CENTRE

AbstractThe Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted. Targeting the Hh signalling pathway may pave the way for successful IBD treatment. In this review, we introduce the molecular mechanisms underlying the Hh signalling pathway and its role in maintaining intestinal homeostasis. Then, we present interactions between the Hh signalling and other pathways involved in IBD and colitis-associated colorectal cancer (CAC), such as the Wnt and nuclear factor-kappa B (NF-κB) pathways. Furthermore, we summarise the latest research on Hh signalling associated with the occurrence and progression of IBD and CAC. Finally, we discuss the future directions for research on the role of Hh signalling in IBD pathogenesis and provide viewpoints on novel treatment options for IBD by targeting Hh signalling. An in-depth understanding of the complex role of Hh signalling in IBD pathogenesis will contribute to the development of new effective therapies for IBD patients.

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The Effect of Mesalamine and Nicotine in the Treatment of Inflammatory Bowel Disease

Annals of Pharmacotherapy ◽

10.1177/106002809703100719 ◽

1997 ◽

Vol 31 (7-8) ◽

pp. 907-913 ◽

Cited By ~ 9

Author(s):

Charles R. Bonapace ◽

David A. Mays

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Relapse Rate ◽

Bowel Disease ◽

Therapeutic Agent ◽

Active Ulcerative Colitis ◽

Steroid Dependence ◽

Inflammatory Bowel

OBJECTIVE: To characterize the usefulness of mesalamine and nicotine in the treatment of active ulcerative colitis and inactive Crohn's disease. DATA SOURCES: Citations were selected from the MEDLINE database. Only those involving human subjects, inflammatory bowel disease, and available in English were selected. STUDY SELECTION: Selection criteria consisted of clinical trials and review articles assessing the effects of mesalamine and nicotine in active ulcerative colitis or inactive Crohn's disease and the utility of reducing steroid dependence or relapse rate. Less than 20% of the articles identified met the selection criteria. DATA SYNTHESIS: In patients with inactive Crohn's disease, mesalamine 2 g/d significantly reduced the risk of relapse in high-relapse-risk patients compared with placebo, reducing the relapse rate from 71% to 55%, but was ineffective in preventing recurrence of inactive Crohn's disease following surgical resection. Mesalamine 4 g/d was effective in decreasing weaning failure due to steroid dependence by 67%, although the relapse rate was not significant compared with placebo at the end of 12 months. Following surgical resection, mesalamine was unable to significantly reduce the incidence of recurrence compared with placebo at the end of 1 year. In patients with active ulcerative colitis, oral mesalamine 2 and 4 g/d was superior to placebo in inducing remission compared with placebo. Among patients with prior steroid or sulfasalazine treatment, rectal mesalamine 4 g hs achieved a remission rate of 78% in more than 12 weeks of therapy. Other studies have not found a dose—response relationship with lower dosages of mesalamine. Whereas nicotine 15–25 mg/d administered as a transdermal patch produced greater symptomatic improvement in active ulcerative colitis compared with placebo, nicotine 15 mg/16 h produced results no different from those with placebo in maintaining remission in inactive ulcerative colitis. Nicotine appears to have an adverse effect on the course of Crohn's disease and is not recommended. CONCLUSIONS: Mesalamine has demonstrated clinical effectiveness as a therapeutic agent in the treatment of active ulcerative colitis and inactive Crohn's disease. Although its relationship to inflammatory bowel disease has been known for many years, the usefulness of nicotine for the treatment of active ulcerative colitis requires further exploration before it can be recommended as a therapeutic agent.

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Revisiting Inflammatory Bowel Disease: Pathology, Treatments, Challenges and Emerging Therapeutics Including Drug Leads from Natural Products

Journal of Clinical Medicine ◽

10.3390/jcm9051273 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1273 ◽

Cited By ~ 6

Author(s):

Karma Yeshi ◽

Roland Ruscher ◽

Luke Hunter ◽

Norelle L. Daly ◽

Alex Loukas ◽

...

Keyword(s):

Health Care ◽

Inflammatory Bowel Disease ◽

Natural Products ◽

Bowel Disease ◽

Inflammatory Diseases ◽

Treatment Options ◽

Mucosal Healing ◽

Main Challenge ◽

Long Term Treatment ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic and life-long disease characterized by gastrointestinal tract inflammation. It is caused by the interplay of the host’s genetic predisposition and immune responses, and various environmental factors. Despite many treatment options, there is no cure for IBD. The increasing incidence and prevalence of IBD and lack of effective long-term treatment options have resulted in a substantial economic burden to the healthcare system worldwide. Biologics targeting inflammatory cytokines initiated a shift from symptomatic control towards objective treatment goals such as mucosal healing. There are seven monoclonal antibody therapies excluding their biosimilars approved by the US Food and Drug Administration for induction and maintenance of clinical remission in IBD. Adverse side effects associated with almost all currently available drugs, especially biologics, is the main challenge in IBD management. Natural products have significant potential as therapeutic agents with an increasing role in health care. Given that natural products display great structural diversity and are relatively easy to modify chemically, they represent ideal scaffolds upon which to generate novel therapeutics. This review focuses on the pathology, currently available treatment options for IBD and associated challenges, and the roles played by natural products in health care. It discusses these natural products within the current biodiscovery research agenda, including the applications of drug discovery techniques and the search for next-generation drugs to treat a plethora of inflammatory diseases, with a major focus on IBD.

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P336 Behavioural treatment options for psychological comorbidities in patients with inflammatory bowel disease: a systematic literature review

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjy222.460 ◽

2019 ◽

Vol 13 (Supplement_1) ◽

pp. S269-S270

Author(s):

L Keefer ◽

R Cheung ◽

M Bernauer ◽

D Patel ◽

M Dubinsky

Keyword(s):

Inflammatory Bowel Disease ◽

Literature Review ◽

Systematic Literature Review ◽

Bowel Disease ◽

Treatment Options ◽

Behavioural Treatment ◽

Psychological Comorbidities ◽

Inflammatory Bowel

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P664 The impact of vedolizumab on extra-intestinal manifestations in inflammatory bowel disease patients: A real-life experience of a single-centre cohort

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.792 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S546-S547

Author(s):

M TRUYENS ◽

J Geldof ◽

G Dewitte ◽

E Glorieus ◽

G Varkas ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Disease Activity ◽

Bowel Disease ◽

Life Experience ◽

Real Life ◽

Intestinal Disease ◽

Single Centre ◽

Clinical Evolution ◽

Inflammatory Bowel ◽

The Impact

Abstract Background Vedolizumab (VDZ), a gut-specific anti-integrin, is approved as a treatment for moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). Extra-intestinal manifestations (EIMs) are frequently associated with inflammatory bowel disease (IBD). However, the effect of VDZ on EIMs remains unknown. The aim of the current study was to describe the prevalence of EIMs in IBD patients at VDZ initiation, the evolution during continued treatment as well as the occurrence of new EIMs. Methods A single-centre study was performed in IBD patients who were started on VDZ between May 2010 and February 2019. Retrospectively, the physician-reported EIMs and intestinal disease activity (clinical and endoscopic) were assessed at baseline, 6 months and 1 year after the start of VDZ. Results The cohort consisted of 134 patients, including 77 CD patients, 56 UC patients and 1 patient with unclassified IBD. At VDZ initiation EIMs were assessed in 127 patients and 17.3% had ≥ 1 EIM: 9 hepatic EIMs (2 patients with toxic hepatitis, 2 with autoimmune hepatitis and 5 with PSC), 7 arthropathies (6 patients with axial spondyloarthropathy and 1 with peripheral arthritis), 3 non-further specified axial or peripheral arthralgias and 3 cutaneous EIMs (urticaria, psoriasis and erythema nodosum). Clinical evolution of the EIMs is reported in Table 1, assessment of intestinal disease activity in Table 2. During follow-up, 23 new EIMs were seen, mainly arthralgia, which was often transient. VDZ was stopped in 39/130 (30%) patients due to active intestinal disease in 32 patients, patients’ choice (n = 1) or because of deep disease remission (n = 1). In five patients, VDZ was stopped because of insufficient control of EIM. Conclusion A good clinical intestinal response was observed. However, the clinical evolution of EIMs appears unaffected by the use of VDZ in our cohort. Prospective data are needed to confirm these results.

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