Dataset Information

Pharmacogenomics: An Update on Biologics and Small-Molecule Drugs in the Treatment of Psoriasis.

ABSTRACT: Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, studies performed on genes involved in the metabolism of biological drugs (tumor necrosis factor inhibitors and cytokines inhibitors) and small molecules (apremilast, dimethyl fumarate, and tofacitinib) have provided conflicting results, and further investigations are necessary in order to establish a set of biomarkers to be introduced into clinical practice.

SUBMITTER: Caputo V

PROVIDER: S-EPMC8470543 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Pharmacogenomics: An Update on Biologics and Small-Molecule Drugs in the Treatment of Psoriasis.

Caputo Valerio V Strafella Claudia C Cosio Terenzio T Lanna Caterina C Campione Elena E Novelli Giuseppe G Giardina Emiliano E Cascella Raffaella R

Genes 20210910 9

Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, st ...[more]

PMID: 34573380

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Project description:Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th-20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology.

Project description:Background: Biologics and small-molecule drugs have become increasingly accepted worldwide in the treatment of axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). However, a quantitative multiple comparison of their efficacy and safety is lacking. This study aims to provide an integrated assessment of the relative benefits and safety profiles of these drugs in axSpA treatment. Methods: We included randomized clinical trials that compared biologics and small-molecule drugs in the treatment of axSpA patients. The primary outcomes assessed were efficacy, including the Assessment of SpondyloArthritis International Society (ASAS) improvement of 20% (ASAS20) and 40% (ASAS40). Safety outcomes included treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). We used the surface under the cumulative ranking (SUCRA) curve value and ranking plot to evaluate and rank clinical outcomes and safety profiles of different treatments. The two-dimensional graphs were illustrated to visually assess both the efficacy (horizontal axis) and safety (vertical axis) of each intervention. Results: Our analysis included 57 randomized clinical trials involving a total of 11,787 axSpA patients. We found that seven drugs (TNFRFc, TNFmAb, IL17Ai, IL17A/Fi, IL17RAi, JAK1/3i, and JAK1i) were significantly more effective in achieving ASAS20 response compared to the placebo (PLA). Except for IL17RAi, these drugs were also associated with higher ASAS40 responses. TNFmAb demonstrated the highest clinical response efficacy among all the drugs. Subgroup analyses for AS and nr-axSpA patients yielded similar results. IL17A/Fi emerged as a promising choice, effectively balancing efficacy and safety, as indicated by its position in the upper right corner of the two-dimensional graphs. Conclusion: Our findings highlight TNFmAb as the most effective biologic across all evaluated efficacy outcomes in this network meta-analysis. Meanwhile, IL17A/Fi stands out for its lower risk and superior performance in achieving a balance between efficacy and safety in the treatment of axSpA patients.

Dataset Information

Pharmacogenomics: An Update on Biologics and Small-Molecule Drugs in the Treatment of Psoriasis.

Publications

Pharmacogenomics: An Update on Biologics and Small-Molecule Drugs in the Treatment of Psoriasis.

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