A Practical Guide to the Safety and Monitoring of New IBD Therapies

Click, Benjamin; Regueiro, Miguel

doi:10.1093/ibd/izy313

Cited by 45 publications

(34 citation statements)

References 78 publications

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“…Research on IBD therapy has advanced on the past few years, and inflammatory cytokines or specific cellular pathways such as JAK/STAT and phosphodiesterase-4 have all been explored as potential targets for IBD treatment ( Pekow, 2017 ). Still, it is unlikely that a significant number of such newly-developed drugs aimed at interacting with the aforementioned targets will reach clinical practice, as several of these compounds do not display satisfactory remission rates or lead to severe adverse effects, such as increased risk for infection, malignancies or immunological disorders in larger clinical trials ( Pekow, 2017 ; Click and Regueiro, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone-Mediated Attenuation of Experimental Colitis Relies on Cleaving of Annexin A1 Released by Macrophages

et al. 2020

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Ulcerative colitis and Crohn’s disease are chronic inflammatory bowel diseases (IBDs) which burden health systems worldwide; available pharmacological therapies are limited and cost-intensive. Use of peroxisome proliferator activated-receptor γ (PPARγ) ligands for IBD treatment, while promising, lacks solid evidences to ensure its efficacy. Annexin A1 (AnxA1), a glucocorticoid-modulated anti-inflammatory protein, plays a key role on IBD control and is a potential biomarker of IBD progression. We here investigated whether effects of pioglitazone, a PPARγ ligand, rely on AnxA1 actions to modulate IBD inflammation. Experimental colitis was evoked by 2% dextran sodium sulfate (DSS) in AnxA1 knockout (AnxA1−/−) or wild type (WT) C57BL/6 mice. Clinical and histological parameters were more severe for AnxA−/− than WT mice, and 10 mg/kg pioglitazone treatment attenuated disease parameters in WT mice only. AnxA1 expression was increased in tissue sections of diseased WT mice, correlating positively with presence of CD68+ macrophages. Metalloproteinase-9 (MMP-9) and inactive 33 kDa AnxA1 levels were increased in the colon of diseased WT mice, which were reduced by pioglitazone treatment. Cytokine secretion, reactive oxygen species generation and MMP-9 expression caused by lipopolysaccharide (LPS) treatment in AnxA1-expressing RAW 264.7 macrophages were reduced by pioglitazone treatment, effects not detected in AnxA1 knockdown macrophages. LPS-mediated increase of AnxA1 cleaving in RAW 264.7 macrophages was also attenuated by pioglitazone treatment. Finally, pioglitazone treatment increased extracellular signal-regulated kinase (ERK) phosphorylation in AnxA1-expressing RAW 264.7 macrophages, but not in AnxA1-knockdown macrophages. Thus, our data highlight AnxA1 as a crucial factor for the therapeutic actions of pioglitazone on IBDs.

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Section: Discussionmentioning

confidence: 99%

Pioglitazone-Mediated Attenuation of Experimental Colitis Relies on Cleaving of Annexin A1 Released by Macrophages

et al. 2020

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“…Terapie te koncentrują się przede wszystkim na łagodzeniu stanu zapalnego, osłabianiu bólów brzucha i ograniczaniu występowania biegunek. Do najczęściej stosowanych leków zalicza się 5-aminosalicylany (5-ASA), glikokortykosteroidy, immunosupresanty oraz specyficzne przeciwciała przeciwko prozapalnym cytokinom [4][5][6]. Również, w pewnych okolicznościach, gdy terapia farmakologiczna kończy się niepowodzeniem, można rozważyć operację.…”

Section: Wprowadzenieunclassified

Polifenole w leczeniu nieswoistych chorób zapalnych jelit

Chojnacka

Laskowska

2020

Postepy Biochem

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Nieswoiste choroby zapalne jelit (NChZJ), obejmujące chorobę Leśniowskiego-Crohna (ChLC) oraz wrzodziejące zapalenie jelita grubego (WZJG), są przewlekłymi schorzeniami onieznanej etiologii, którym przypisuje się wieloczynnikowe podłoże. Choroby te niosą zesobą ryzyko poważnych powikłań oraz zwiększają ryzyko wystąpienia nowotworu jelitagrubego, a w ostatnich latach odnotowuje się podwyższony wskaźnik zapadalności na NChZJ.Jak dotąd nie ma skutecznej i dobrze zdefiniowanej terapii leczenia NChZJ, a obecniedostępne leki umożliwiają głównie leczenie objawowe. Dodatkowo leczenie konwencjonalnenie zawsze przynosi oczekiwane korzyści, co więcej często wiąże się z nieprzyjemnymiskutkami ubocznymi. Obecnie prowadzone są badania, w których naukowcy koncentrują sięna niekonwencjonalnych formach leczenia NChZJ, gdzie terapie oparte są o naturalneprodukty. Interesujące są preparaty bogate w związki polifenolowe, gdyż wykazują oneszereg właściwości biologicznych, nazywane są „zmiataczami wolnych rodników”, zewzględu na silne działanie antyoksydacyjne, ale również przeciwzapalne i bakteriobójcze.Prowadzone badania kliniczne sugerują, iż polifenole mogą łagodzić objawy, czy zapobiegaćnawrotom NChZJ.

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“…5 Their use resulted in improved outcomes and lower requirements for surgical intervention. 6,7 Although concerns have been raised about the long-term safety of TNFi's, 8 they remain the preferred class of biologics in certain indications, such as perianal fistulizing CD or acute severe UC. 9,10 The high cost of these agents constitutes the main limiting step in accessing them for many patients.…”

Section: Introductionmentioning

confidence: 99%

<p>Biosimilars to Antitumor Necrosis Factor Agents in Inflammatory Bowel Disease</p>

Sulais

AlAmeel

2020

BTT

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Anti-tumor Necrosis Factor (anti-TNF) agents are the backbone treatment of moderate to severe cases of inflammatory bowel disease. One of the main drawbacks of these agents is the high cost. The introduction of biosimilar products to anti-TNF agents is expected to lower the cost. Health care providers ought to be aware of the available data that addresses the safety and efficacy of biosimilars in IBD patients. This article outlines the current evidence-based data regarding the available biosimilar products, their safety, efficacy and how to deal with patients' concerns.

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A Practical Guide to the Safety and Monitoring of New IBD Therapies

Cited by 45 publications

References 78 publications

Pioglitazone-Mediated Attenuation of Experimental Colitis Relies on Cleaving of Annexin A1 Released by Macrophages

Pioglitazone-Mediated Attenuation of Experimental Colitis Relies on Cleaving of Annexin A1 Released by Macrophages

Polifenole w leczeniu nieswoistych chorób zapalnych jelit

<p>Biosimilars to Antitumor Necrosis Factor Agents in Inflammatory Bowel Disease</p>

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