Current misunderstandings in the management of ulcerative colitis

Ochsenkühn, Thomas; D’Haens, Geert R.

doi:10.1136/gut.2010.218180

Cited by 38 publications

(19 citation statements)

References 51 publications

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“…With the current data and clinical experience available in UC, especially with anti‐TNF therapy, clinicians have been able to clarify many of the misunderstandings around the management of UC. Many of these misunderstandings have been outlined in the review by Ochsenkuhn and D'Haens . Relating to this review, one of the main misunderstandings is that anti‐TNF therapy is less effective in UC compared with CD.…”

Section: Present: What Does Anti‐tnf Treatment In Uc Currently Look Lmentioning

confidence: 93%

Review article: the role of anti‐TNF in the management of ulcerative colitis – past, present and future

Danese

Colombel

Peyrin–Biroulet

et al. 2013

Aliment Pharmacol Ther

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Summary Background Until recently, the management of ulcerative colitis (UC) consisted of the stepwise use of mesalazine, corticosteroids and immunomodulators, or consideration of surgery. Anti‐tumour necrosis factor (TNF) agents are recent additions to the UC‐treatment algorithm. Aim To provide clinicians with a review of the role of anti‐TNFs in UC, discussing how the drug(s) were used in the past, their current use and to determine their future role. Methods The scientific literature was reviewed to evaluate data on the use of anti‐TNFs in UC. Results In this review, we report how the management of UC has changed with the availability of anti‐TNFs. The results from landmark anti‐TNF trials have impacted clinical practice, leading to a readjustment of treatment goals. In addition, experience from clinical trials and local real‐life cohorts have helped to clarify some misunderstandings in the management of UC. New anti‐TNFs are on the horizon but questions still remain on the future role of anti‐TNFs with regard to impact on disability, digestive damage and the possible development of risk matrices. Experiences from the use of anti‐TNFs in Crohn's disease (for example, combination therapy and early treatment) now need to be addressed in UC. Conclusions The use of anti‐TNFs in the management of UC has matured rapidly. Clinical experience has helped shape the current role of anti‐TNFs, but more clinical research is needed to optimise their future role.

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Section: Present: What Does Anti‐tnf Treatment In Uc Currently Look Lmentioning

confidence: 93%

Review article: the role of anti‐TNF in the management of ulcerative colitis – past, present and future

Danese

Colombel

Peyrin–Biroulet

et al. 2013

Aliment Pharmacol Ther

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“…The beneficial effect of live E. coli may provide clues to the cause of UC (21). The use of anti-TNF antibodies in UC is less effective than in Crohn's disease (22). Immunosuppressive therapy is an alternative choice for patients with UC.…”

Section: Discussionmentioning

confidence: 99%

CBLB502 administration protects gut mucosal tissue in ulcerative colitis by inhibiting inflammation

Xu¹,

Dong

et al. 2016

Ann. Transl. Med.

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Background: Ulcerative colitis (UC) is a nonspecific inflammatory disease for which medications and therapeutic strategies have only been moderately successful. CBLB502, a toll-like receptor 5 (TLR5) agonist derived from Salmonella flagellin, exhibits anticancer and radioprotective activities via modulation of TLRs and the nuclear factor kappa B (NF-κB) signaling pathway and can protect against acute renal ischemic failure. In this study, we intend to examine the effects of CBLB502 on both TLR responses and the interleukin (IL) and NF-κB signaling pathways in UC treatment.Methods: The UC mouse model was prepared in BALB/c mice by administering 2,4,6-trinitrobenzene sulfonic acid (TNBS). CBLB502 was used as the therapeutic drug. After CBLB502 therapy, the IL and tumor necrosis factor-α (TNF-α) levels were measured by ELISA. Total RNA and protein of colon samples was extracted.Results: We found that CBLB502 had a distinctive therapeutic effect in the UC model. In control group animals, IL-10 expression in serum was 91.48±24.38 ng/mL; this was higher than in the model group (59.36±14.46 ng/mL, P<0.05) or the treatment group (54.29±5.83 ng/mL, P<0.05). In model group animals, the concentration of TNF-α in serum was 140.11±12.70 ng/mL, which was lower than protein levels in the control group (173.86±29.26 ng/mL, P<0.05). The mRNA levels of TLR1,2,3,4,6,7,8, and 9 in the CBLB502 treatment group were significantly lower than in the model group (P<0.05). Western blot revealed that CBLB502 also reduced NF-κB expression in the mouse colon, but that NF-κB expression was not significantly lower than the model group.Conclusions: CBLB502 can reduce mucosal damage induced by TNBS and inhibit inflammation and TLR expression. The inhibition of UC by CBLB502 is strictly TLR-IL-dependent and is dose-dependent within the efficacious dose range. Therefore, our results suggested that CBLB502 might be a candidate drug for the treatment of UC.

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“…Patients who fail both conventional and TNF-inhibitor therapy typically have no other medical therapeutic options available to them and up to 40% [11] may progress to surgery [12]. However, people may be reluctant to consider surgery due to the potential serious post-surgery complications such as bleeding, faecal incontinence, depression, distorted body image, sexual dysfunction, female infertility, pouchitis, pouch leakage, pelvic abscesses, pouch fistulae, small bowel obstruction and anastomotic stricture [13]. Current treatment options are also associated with safety concerns associated with long term use of corticosteroids, immunomodulators and TNF-inhibitors including immunosuppression, osteoporosis and lymphoma [14;15].…”

Section: Current Treatmentmentioning

confidence: 99%

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

et al. 2015

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As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost-effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost-effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from the GEMINI1 trial, which is a Phase III, multicentre, randomised, doubleblind, placebo-controlled trial designed to evaluate the efficacy and safety of vedolizumab as an induction and maintenance treatment in patients with moderate-to-severe active UC who had an inadequate response to, loss of response to, or intolerance to conventional therapy or anti-Tumour necrosis factor-alpha (TNF-). The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post-hoc subgroup analyses, patients with or without prior anti-TNF-therapy, vedolizumab performed better then placebo (p-value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab and the frequency and types of adverse events were similar between the vedolizumab and placebo group but the evidence was limited to shortterm follow-up. There were a number of limitations and uncertainties in the clinical evidence base which warrant caution in its interpretation. In particular, the post-hoc subgroup analyses and high dropout rates in the maintenance phase of the GEMINI1 trial. The company also presented a network meta-analysis of vedolizumab versus other biologics therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects since fixed effects models were Key Points for Decision Makers Vedolizumab appears to be more effective in both the induction and maintenance phase compared with placebo in patients with moderate-to-severe active ulcerative colitis who have had an inadequate response to, loss of response to, or intolerance to conventional therapy or TNF-inhibitor. However, the subgroup analyses for patients with or without prior TNF-inhibitor therapy were post-hoc and the study was not powered for these assessments.  The findings of the network meta-analysis of vedolizumab versus TNF-inhibitor are limited due to a number of uncertainties in treatment effects. In addition, there is currently no head-to-head randomised 3 controlled trial comparing vedolizumab to other biologic therapies indicated for moderate-to-severe ulcerative colitis.  The National Institute for Health and Care Excellence (NICE) Appraisal Committee recommended vedolizumab within its licence indication but only if the company provides vedolizumab with the discount agr...

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Current misunderstandings in the management of ulcerative colitis

Abstract: Past and ongoing therapeutic concepts for ulcerative colitis have only been moderately successful.

Cited by 38 publications

References 51 publications

Review article: the role of anti‐TNF in the management of ulcerative colitis – past, present and future

Review article: the role of anti‐TNF in the management of ulcerative colitis – past, present and future

CBLB502 administration protects gut mucosal tissue in ulcerative colitis by inhibiting inflammation

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

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