A population pharmacokinetic (PK) analysis of ABX-IL8, a fully human monoclononal IGG antibody, in psoriasis patients

Wang, B.; Roskos, L; Osborn, Kent G.; Lu, Hong; Kim, M.; Pasumarthi, R.; Raie, N.; Tabrizi, M J Nazemi

doi:10.1016/j.clpt.2004.12.240

Cited by 3 publications

(1 citation statement)

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“…Similarly, ABX-IL8 is a fully human IgG 2 monoclonal antibody that binds to human IL-8 with high affinity and specificity and is currently in Phase II clinical investigation for treatment of psoriasis by Abgenix (Fremont, CA, USA). 38 Strikingly, Kim et al 39 found that pretreatment with fluvastatin and simvastatin inhibited migration of human CD4 + T cells towards CCL20 in a chemotaxis migration assay. These findings suggest that these drugs may be of benefit in alleviating psoriasis via interrupting the CCL20/chemokine receptor 6 (CCR6) chemotactic interaction, thus inhibiting infiltration of T H 17 cells.…”

Section: Discussionmentioning

confidence: 99%

Reanalysis of microarray data reveals insights into altered transcriptional activity of T helper 17 and regulatory T cell signaling in psoriasis

Kotb¹,

Meharg²,

Barker³

et al. 2013

PTT

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Identifying differential expression of genes in psoriatic and healthy skin by microarray data analysis is a key approach to understand the pathogenesis of psoriasis. Analysis of more than one dataset to identify genes commonly upregulated reduces the likelihood of false positives and narrows down the possible signature genes. Genes controlling the critical balance between T helper 17 and regulatory T cells are of special interest in psoriasis. Our objectives were to identify genes that are consistently upregulated in lesional skin from three published microarray datasets. We carried out a reanalysis of gene expression data extracted from three experiments on samples from psoriatic and nonlesional skin using the same stringency threshold and software and further compared the expression levels of 92 genes related to the T helper 17 and regulatory T cell signaling pathways. We found 73 probe sets representing 57 genes commonly upregulated in lesional skin from all datasets. These included 26 probe sets representing 20 genes that have no previous link to the etiopathogenesis of psoriasis. These genes may represent novel therapeutic targets and surely need more rigorous experimental testing to be validated. Our analysis also identified 12 of 92 genes known to be related to the T helper 17 and regulatory T cell signaling pathways, and these were found to be differentially expressed in the lesional skin samples.

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Section: Discussionmentioning

confidence: 99%

Reanalysis of microarray data reveals insights into altered transcriptional activity of T helper 17 and regulatory T cell signaling in psoriasis

Kotb¹,

Meharg²,

Barker³

et al. 2013

PTT

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Interspecies Scaling of Therapeutic Monoclonal Antibodies: Initial Look

Ling¹,

Zhou²,

Jiao³

et al. 2009

The Journal of Clinical Pharma

132

122

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The authors evaluated interspecies scaling for the prediction of human clearance of 18 therapeutic monoclonal antibodies (mAbs). Human and monkey/chimpanzee data of 14 mAbs were classified based on the targeted antigens (soluble or membrane bound). Simple allometry and/or a time-invariant method (elementary Dedrick plot) were performed. Results indicate that human clearance might be accurately predicted from monkey data for mAbs targeting soluble receptors or membrane-bound receptors with limited tissue distribution using simplified allometry. The optimal exponents were estimated to be 0.85 or 0.90. If nonlinearity is anticipated at the human efficacious dose, pharmacokinetic parameters obtained at high doses in animals might not be sufficient for full pharmacokinetic characterization and prediction. Using prespecified criteria, including predicted human clearance (< or = or > 10 mL/d/kg), simplified allometric scaling might be helpful in predicting the effect of receptor-mediated clearance for mAbs targeting membrane-bound antigens. Furthermore, simplified allometry and an elementary Dedrick plot provide similar results in predicted clearance. Given the significant advantages offered by simplified allometry, it should be used when data are available from only 1 species. When reasonable data from > or =3 species are available, traditional allometry should be explored. Overall, clearance prediction is useful for human dose prediction in drug discovery and development.

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Immunomodulators in the Treatment of Psoriasis

Maniyan¹,

Sreejith²,

Neena³

et al. 2020

J. Drug Delivery Ther.

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Psoriasis is a chronic T lymphocyte mediated systemic inflammatory disease characterised by recurrent exacerbations and remission of thickened, erythematous and scaling plaque and multiple comorbidities. Based on morphology and extend of involvement dermatosis may range from innocuous lesion to wide spread life threatening pustular and erythrodermic forms. Psoriasis is a multifactorial skin disease and it involves a complex pathogenesis. It can be explained by a immunological disregulation of cell function along with differentiation or proliferation of keratinocyte. Psoriasis treatment aims to reduce skin inflammation and to clear skin. Conventional therapy usually includes topical, light and systemic medications. All the three therapies are found to be good for the treatment but are associated with a number of side effects like increased skin sensitivity, burning, skin staining, xerosis and alopecia etc. Nowadays various recent therapeutic advances are attempting to control the T cell expression by the suppression of same and are correlates with the clinical remission. Immunomodulators and biological therapy contribute a new way for psoriasis therapy. These drugs are more safer, effective and selective immunosuppressive agents as compared to conventional agents. This review summarisesthe variousimmunomodulators used in the treatment of psoriasis Keywords: Psoriasis, conventional therapy, immunomodulators

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A population pharmacokinetic (PK) analysis of ABX-IL8, a fully human monoclononal IGG antibody, in psoriasis patients

Cited by 3 publications

References 0 publications

Reanalysis of microarray data reveals insights into altered transcriptional activity of T helper 17 and regulatory T cell signaling in psoriasis

Reanalysis of microarray data reveals insights into altered transcriptional activity of T helper 17 and regulatory T cell signaling in psoriasis

Interspecies Scaling of Therapeutic Monoclonal Antibodies: Initial Look

Immunomodulators in the Treatment of Psoriasis

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