# Sporiasis Pathogenesis and Treatment
## 3 Therapy
### Biologics
#### 3.2.1 TNF-\(\alpha\)  
TNF-\(\alpha\) inhibitors have been available for over a decade. They are considered the first-generation biologics, and are effective for plaque psoriasis and psoriatic arthritis. TNF-\(\alpha\) inhibitors are still the standard used to evaluate drug efficacy in psoriasis clinical research. There are currently four drugs in this category: etanercept, infliximab, adalimumab, and certolizumab. Etancercept is unique in the biologics category in that it is not a monoclonal antibody, but rather a recombinant human fusion protein. The receptor portion for the TNF-\(\alpha\) ligand is fused to the Fc portion of an IgG1 antibody. It was the first TNF-\(\alpha\) inhibitor approved by the United States Food and Drug Administration (FDA) for psoriasis. Infliximab is a chimeric monoclonal IgG1 antibody, and adalimumab is a fully human monoclonal IgG1 antibody. They neutralize TNF-\(\alpha\) activity by binding to its soluble and membrane-bound form. These drugs are particularly employed to treat psoriatic arthritis, and show a similar efficacy. In the treatment of psoriasis, they show different PASI 75 response rates: 52% for etanercept, 59% for adalimumab, and 80% for infliximab. Infliximab shows superiority in terms of efficacy when compared to the other TNF-\(\alpha\) inhibitors, and when compared with ustekinumab, it showed a similar performance [195]. The chimeric nature of infliximab might contribute to a higher immunogenic potential of the drug, which in turn might influence drug survival. Certolizumab pegol is a pegylated Fab' fragment of a humanized monoclonal antibody against TNF-\(\alpha\). PEGylation is the covalent conjugation of proteins with polyethylene glycol (PEG), and is attributed a number of biopharmaceutical improvements, including increased half-life and reduced immunogenicity [196]. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Drug** & **Mechanism** & **Application** \\ \hline Methotrexate & Dihydrofolate reductase inhibition blocks purine biosynthesis; induction of lymphocyte apoptosis & s.c./oral \\ Cyclosporin & Calineurin inhibition leading to reduced IL-2 & Oral \\ Acitretin & Normalization of keratinocyte proliferation/differentiation through retinoid & Oral \\  & receptor binding & Oral \\  & Intracellular glutathione, modulation of Nrf2, NF-\(\kappa\)B, and HIF-1\(\alpha\); promoting a & \\ Fumarate & shift from a pro-inflammatory Th1/Th17 response to an & Oral \\  & anti-inflammatory/regulatory Th2 response. & \\ Apremilast & PDE4 inhibitor increases inracellular cAMP levels in immune and non-immune & Oral \\  & cell types modulating inflammation & \\  & Etancercept & Dimeric human fusion protein mimicking TNF-\(\alpha\)R & s.c. \\ Infliximab & Chimeric IgG1\(\kappa\) monoclonal antibody that binds to soluble and transmembrane & i.v. \\ Adalimumab & & Human monoclonal antibody against TNF-\(\alpha\) & s.c. \\ Certolizumab & Fab portion of humanized monoclonal antibody against TNF-\(\alpha\) conjugated to & s.c. \\  & polyethylene glycol & \\ Ustekinumab & Human IgG1k monoclonal antibody that binds with specificity to the p40 protein & s.c. \\  & subunit used by both the interleukin (IL)-12 and IL-23 cytokines IL-12/IL-23 p40 & s.c. \\ Tildrakizumab & Humanized IgG1k, which selectively blocks IL-23 by binding to its p19 subunit & s.c. \\ Guselkumab & Human immunoglobulin G1 lambda (IgG1\(\alpha\)) monoclonal antibody that & s.c. \\  & selectively blocks IL-23 by binding to its p19 subunit & s.c. \\  & Humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically & s.c. \\  & cacextinumab & Human IgG1\(\kappa\) monoclonal antibody against IL-17A & s.c. \\  & Humanized, immunoglobulin G4\(\kappa\) monoclonal antibody selectively binds and & s.c. \\  & neutralizes IL-17A & s.c. \\  & Proximal monoclonal IgG2 antibody directed at the IL-17 RA & s.c. \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Drugs available for psoriasis therapy.