Infliximab in the treatment of Crohn's disease

Poggioli, Gilberto; Laureti, Silvio; Campieri, Massimo; Pierangeli, Filippo; Gionchetti, Paolo; Ugolini, Federica; Gentilini, Lorenzo; Bazzi, Piero; Rizzello, Fernando; Coscia, Maurizio

doi:10.2147/tcrm.2007.3.2.301

Cited by 35 publications

(23 citation statements)

References 59 publications

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“…Infliximab has been proven to be efficient in UC and CD by blocking TNF-alpha activity [47][48][49]. Our results confirmed the mechanism of infliximab action, including induction of apoptosis in T cells, inhibition of cytokine and chemokine expression, as well as cell-cell signaling and immune cell trafficking [27], and its efficacy in these diseases.…”

Section: Discussionsupporting

confidence: 81%

“…The Active Ulcerative Colitis (UC) Trial 1 (ACT1) study, as well as several other trials, have proven that infliximab is effective for the treatment of moderate to severe UC [48]. Crohn's disease (CD) is also considered as a target for infliximab, and its efficacy was also demonstrated in clinical trials [49]. Since COPD and sarcoidosis are also characterized by an abnormal inflammatory response [20], particularly mediated by TNF-alpha and other cytokines [50,51], we aimed to evaluate similarities of transcriptome landscapes in UC, CD, COPD, and sarcoidosis and the ability of infliximab to target pathological processes in COPD and sarcoidosis as well.…”

Section: Evaluation Of Infliximab As a Potential Therapeutics For Ulcmentioning

confidence: 99%

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Transcriptome-Guided Drug Repositioning

et al. 2019

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Drug repositioning can save considerable time and resources and significantly speed up the drug development process. The increasing availability of drug action and disease-associated transcriptome data makes it an attractive source for repositioning studies. Here, we have developed a transcriptome-guided approach for drug/biologics repositioning based on multi-layer self-organizing maps (ml-SOM). It allows for analyzing multiple transcriptome datasets by segmenting them into layers of drug action- and disease-associated transcriptome data. A comparison of expression changes in clusters of functionally related genes across the layers identifies “drug target” spots in disease layers and evaluates the repositioning possibility of a drug. The repositioning potential for two approved biologics drugs (infliximab and brodalumab) confirmed the drugs’ action for approved diseases (ulcerative colitis and Crohn’s disease for infliximab and psoriasis for brodalumab). We showed the potential efficacy of infliximab for the treatment of sarcoidosis, but not chronic obstructive pulmonary disease (COPD). Brodalumab failed to affect dysregulated functional gene clusters in Crohn’s disease (CD) and systemic juvenile idiopathic arthritis (SJIA), clearly indicating that it may not be effective in the treatment of these diseases. In conclusion, ml-SOM offers a novel approach for transcriptome-guided drug repositioning that could be particularly useful for biologics drugs.

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Section: Discussionsupporting

confidence: 81%

Section: Evaluation Of Infliximab As a Potential Therapeutics For Ulcmentioning

confidence: 99%

Transcriptome-Guided Drug Repositioning

et al. 2019

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“…The proportion of patients in the placebo group achieving or maintaining clinical remission or clinical response-100 was substantially higher than that reported in other recent phase II or III studies assessing other agents in CD and using CDAI as the efficacy endpoint. [18][19][20][21][22][23][24][25] This unexpectedly high placebo response prevented a thorough evaluation of the dose-response relationship of tofacitinib in inducing and maintaining response in clinical endpoints and biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials

Panés

Sandborn

Schreiber

et al. 2017

Gut

310

220

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ObjectiveTofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD).DesignWe conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study.Results180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments.ConclusionsPrimary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib.Trial registration numbersNCT01393626 and NCT01393899.

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“…They are common within 1–2 h after an infusion and occur in about 20% of patients [25]. Symptoms include itching, flushing, breathlessness, chest pains, hypertension and headaches.…”

Section: Adverse Effects Of Anti-tnf Therapy In CDmentioning

confidence: 99%

Anti-TNF Therapy in Crohn’s Disease

Adegbola

Sahnan

Warusavitarne

et al. 2018

IJMS

217

173

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Crohn’s disease (CD) accounts for a variety of clinical manifestations or phenotypes that stem from chronic inflammation in the gastrointestinal tract. Its worldwide incidence is increasing including younger or childhood-onset of disease. The natural history of Crohn’s disease is characterized by a remitting and relapsing course that progresses to complications and surgery in most patients. The goals of treatment are to achieve clinical and endoscopic remission, to avoid disease progression and minimise surgical resections. Medical treatment usually features antibiotics, corticosteroids, immunomodulators (thiopurines, methotrexate). Anti-TNF (tumour necrosis factor) therapy was approved for use in Crohn’s disease in 1998, and has changed the paradigm of treatment, leading to improved rates of response and remission in patients. There are significant considerations that need to be borne in mind, when treating patients including immunogenicity, safety profile and duration of treatment.

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Infliximab in the treatment of Crohn's disease

Cited by 35 publications

References 59 publications

Transcriptome-Guided Drug Repositioning

Transcriptome-Guided Drug Repositioning

Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials

Anti-TNF Therapy in Crohn’s Disease

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