The effect of adalimumab for induction of endoscopic healing and normalization of mucosal cytokine gene expression in Crohn's disease

Rismo, Renathe; Olsen, Trine; Ciu, Guanglin; Paulssen, Eyvind J.; Christiansen, Ingrid; Florholmen, Jon; Goll, Rasmus

doi:10.3109/00365521.2012.711853

Cited by 27 publications

(17 citation statements)

References 37 publications

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“…This may demonstrate the effects of the induction therapy itself 20. A study published after EXTEND also showed mucosal healing at week 12 after adalimumab induction therapy 57. Mucosal healing, defined by CDEIS score, has been demonstrated as early as week 4 in a study with infliximab5 and as early as 10 weeks with certolizumab 58.…”

Section: Resultsmentioning

confidence: 93%

Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial

Asgharpour¹,

Cheng²,

Bickston

2013

CEG

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The advent of anti-tumor necrosis factor (TNF) therapies revolutionized the treatment of inflammatory bowel disease. Adalimumab is a subcutaneous anti-TNF agent indicated for use in patients with moderate-to-severe Crohn’s disease and those with moderate-to-severe ulcerative colitis. In both diseases, it can be used for both induction of remission and for maintenance of remission. This review focuses on its use in Crohn’s disease as described in the EXTEND (Extend the Safety and Efficacy of Adalimumab through Endoscopic Healing) trial. Several clinical trials using traditional instruments to measure clinical response have had endoscopic substudies looking for endoscopic healing. The EXTEND trial is the first to use mucosal healing on endoscopy as a primary endpoint for patients with moderate-to-severe Crohn’s disease and baseline ulcerative disease treated with continuous adalimumab. In this well designed trial, the primary endpoint was narrowly missed, but the secondary endpoints further the notion that mucosal healing should be a more mainstream measure of drug efficacy. How this will translate from clinical trials to the clinic is not yet clear, but identifying noninvasive markers for mucosal healing, and understanding the implications of mucosal healing for safety, resource utilization, and quality of life are all worthy targets for further study. The aim of this review is to understand the role of mucosal healing, safety profile, and efficacy in patients treated with anti-TNF therapy, with particular attention to adalimumab and the EXTEND trial.

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Section: Resultsmentioning

confidence: 93%

Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial

Asgharpour¹,

Cheng²,

Bickston

2013

CEG

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“…It was presented that infliximab treatment (5 mg/kg, every 8 weeks for 6 months) to patients after resection of CD showed a decrease in mucosal IL-1β, IL-6 and TNF-α which contributed to the suppressive effect on clinical and endoscopic disease activity (Yamamoto et al 2009). Similarly, six injections of adalimumab to 70 CD patients (80 mg at week 0 and then 40 mg every 2 weeks as subcutaneous injections), another anti-TNF-α antibody, for 10 weeks to patients with CD significantly decreased mucosal mRNA level of TNF-α, INF-γ, IL-17A and IL-23 (Rismo et al 2012). The decreased level of IFN-γ may result from its reduced secretion by T cells and depletion of TNF levels (Agnholt and Kaltoft 2001).…”

Section: Clinical View Of the Anti-oxidative Role Of Drugs Used In Ibmentioning

confidence: 97%

Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases

Piechota-Polańczyk

Fichna

2014

Naunyn-Schmiedeberg's Arch Pharmacol

307

200

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In this review, we focus on the role of oxidative stress in the aetiology of inflammatory bowel diseases (IBD) and colitis-associated colorectal cancer and discuss free radicals and free radical-stimulated pathways as pharmacological targets for anti-IBD drugs. We also suggest novel anti-oxidative agents, which may become effective and less-toxic alternatives in IBD and colitis-associated colorectal cancer treatment. A Medline search was performed to identify relevant bibliography using search terms including: ‘free radicals,’ ‘antioxidants,’ ‘oxidative stress,’ ‘colon cancer,’ ‘ulcerative colitis,’ ‘Crohn’s disease,’ ‘inflammatory bowel disease.’ Several therapeutics commonly used in IBD treatment, among which are immunosuppressants, corticosteroids and anti-TNF-α antibodies, could also affect the IBD progression by interfering with cellular oxidative stress and cytokine production. Experimental data shows that these drugs may effectively scavenge free radicals, increase anti-oxidative capacity of cells, influence multiple signalling pathways, e.g. MAPK and NF-kB, and inhibit pro-oxidative enzyme and cytokine concentration. However, their anti-oxidative and anti-inflammatory effectiveness still needs further investigation. A highly specific antioxidative activity may be important for the clinical treatment and relapse of IBD. In the future, a combination of currently used pharmaceutics, together with natural and synthetic anti-oxidative compounds, like lipoic acid or curcumine, could be taken into account in the design of novel anti-IBD therapies.

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“…These values have been generated by consensus among authors 54 in distinction to objective data. 53 Given the high degree of correlation between the CDEIS and the simplicity of its application, the SES-CD has gained popularity for the assessment of eligibility 55 and outcome 36,[56][57][58][59][60][61][62][63][64] in clinical trials. A modified SES-CD that only examines ulcer size and ulcerated surface area has also been reported.…”

Section: Simple Endoscopic Score In Crohn's Diseasementioning

confidence: 99%

A Systematic Review of Measurement of Endoscopic Disease Activity and Mucosal Healing in Crohnʼs Disease

Khanna

Bouguen

Feagan

et al. 2014

Inflammatory Bowel Diseases

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The effect of adalimumab for induction of endoscopic healing and normalization of mucosal cytokine gene expression in Crohn's disease

Cited by 27 publications

References 37 publications

Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial

Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial

Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases

A Systematic Review of Measurement of Endoscopic Disease Activity and Mucosal Healing in Crohnʼs Disease

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The effect of adalimumab for induction of endoscopic healing and normalization of mucosal cytokine gene expression in Crohn's disease

Cited by 27 publications

References 37 publications

Adalimumab treatment in Crohn&#39;s disease: an overview of long-term efficacy and safety in light of the EXTEND trial

Adalimumab treatment in Crohn&#39;s disease: an overview of long-term efficacy and safety in light of the EXTEND trial

Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases

A Systematic Review of Measurement of Endoscopic Disease Activity and Mucosal Healing in Crohnʼs Disease

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Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial

Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial