Editing Psoriasis (section)

===Systemic agents===
[[Image:Psoriasis infliximab ar1182-2.gif|thumb|Pictures of a person with psoriasis (and [[psoriatic arthritis]]) at baseline and eight weeks after initiation of [[infliximab]] therapy]]
Psoriasis resistant to [[topical|topical treatment]] and [[light therapy|phototherapy]] may be treated with systemic therapies including [[medication]]s by mouth or [[Injection (medicine)|injectable treatments]].<ref name="Dogra2013">{{cite journal | vauthors = Dogra S, Mahajan R | title = Systemic methotrexate therapy for psoriasis: past, present and future | journal = Clinical and Experimental Dermatology | volume = 38 | issue = 6 | pages = 573–88 | date = August 2013 | pmid = 23837932 | doi = 10.1111/ced.12062 | s2cid = 11207097 }}</ref> People undergoing systemic treatment must have regular [[Blood test|blood]] and [[liver function tests]] to check for medication toxicities.<ref name="Dogra2013"/> [[Pregnancy]] must be avoided for most of these treatments.{{medical citation needed|date=July 2023}} The majority of people experience a [[Recrudescence|recurrence]] of psoriasis after systemic treatment is discontinued.{{medical citation needed|date=July 2023}}

<!-- First line treatments -->
Non-biologic systemic treatments frequently used for psoriasis include [[methotrexate]], [[ciclosporin]], [[hydroxycarbamide]], [[fumarate]]s such as [[dimethyl fumarate]], and [[retinoids]].<ref name="Rustin2012">{{cite journal | vauthors = Rustin MH | title = Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data | journal = The British Journal of Dermatology | volume = 167 | issue = Suppl 3 | pages = 3–11 | date = November 2012 | pmid = 23082810 | doi = 10.1111/j.1365-2133.2012.11208.x | s2cid = 22462278 }}</ref> Methotrexate and ciclosporin are [[immunosuppressive drug|medications that suppress the immune system]]; retinoids are synthetic forms of [[vitamin A]]. These agents are also regarded as first-line treatments for [[psoriatic erythroderma]].<ref name="Zattra2012"/> Oral [[corticosteroid]]s should not be used as they can severely flare psoriasis upon their discontinuation.<ref>{{cite web|url=https://www.aad.org/education/basic-derm-curriculum/suggested-order-of-modules/psoriasis|title=Learning module: Psoriasis {{!}} American Academy of Dermatology|website=www.aad.org|access-date=26 March 2017|url-status=live|archive-url=https://web.archive.org/web/20170327075847/https://www.aad.org/education/basic-derm-curriculum/suggested-order-of-modules/psoriasis|archive-date=27 March 2017}}</ref>

<!-- Biologics -->
[[biologic medical product|Biologics]] are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalized immunosuppressive medical therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis.<ref name="Rustin2012"/> These medications are generally well-tolerated, and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis.<ref name="Rustin2012"/><ref name="Griffiths2012"/> However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.<ref name="Rustin2012"/>

Guidelines regard biologics as a third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments.<ref name="Griffiths2012">{{cite journal | vauthors = Griffiths CE | title = Biologics for psoriasis: current evidence and future use | journal = The British Journal of Dermatology | volume = 167 | issue = Suppl 3 | pages = 1–2 | date = November 2012 | pmid = 23082809 | doi = 10.1111/j.1365-2133.2012.11207.x | s2cid = 42598571 }}</ref> The safety of biologics during pregnancy has not been assessed. European guidelines recommend avoiding biologics if a pregnancy is planned; [[TNF inhibitor|anti-TNF]] therapies such as infliximab are not recommended for use in chronic carriers of the [[hepatitis B virus]] or individuals infected with [[HIV]].<ref name="Rustin2012"/>

<!-- Monoclonal antibiodies -->
Several monoclonal [[Antibody|antibodies]] target cytokines, the molecules that cells use to send inflammatory signals to each other. [[tumor necrosis factor α|TNF-α]] is one of the main executor inflammatory cytokines. Four [[monoclonal antibody|monoclonal antibodies]] (MAbs) ([[infliximab]], [[adalimumab]], [[golimumab]], and [[certolizumab pegol]]) and one recombinant TNF-α [[decoy receptor]], [[etanercept]], have been developed to inhibit TNF-α signaling. Additional monoclonal antibodies, such as [[ixekizumab]],<ref>{{cite journal | vauthors = Farahnik B, Beroukhim K, Zhu TH, Abrouk M, Nakamura M, Singh R, Lee K, Bhutani T, Koo J | title = Ixekizumab for the Treatment of Psoriasis: A Review of Phase III Trials | journal = Dermatology and Therapy | volume = 6 | issue = 1 | pages = 25–37 | date = March 2016 | pmid = 26910853 | pmc = 4799032 | doi = 10.1007/s13555-016-0102-0 }}</ref> have been developed against pro-inflammatory cytokines<ref>{{cite journal | vauthors = Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Durez P, Tak PP, Gomez-Reino JJ, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD, Rose K, Haider A, Di Padova F | title = Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis | journal = Science Translational Medicine | volume = 2 | issue = 52 | pages = 52ra72 | date = October 2010 | pmid = 20926833 | doi = 10.1126/scitranslmed.3001107 | doi-access =  | title-link = doi | s2cid = 10132276 }}</ref> and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies.<ref name=Nestle/> IL-12 and IL-23 share a common domain, [[interleukin-12 subunit beta|p40]], which is the target of the [[Food and Drug Administration|FDA-approved]] [[ustekinumab]].<ref name="Prieto2013">{{cite journal | vauthors = Prieto-Pérez R, Cabaleiro T, Daudén E, Ochoa D, Roman M, Abad-Santos F | title = Genetics of psoriasis and pharmacogenetics of biological drugs | journal = Autoimmune Diseases | volume = 2013 | issue = 613086 | pages = 613086 | date = August 2013 | pmid = 24069534 | pmc = 3771250 | doi = 10.1155/2013/613086 | doi-access = free | title-link = doi }}</ref> In 2017 the [[US FDA]] approved [[guselkumab]] for plaque psoriasis.<ref name=FDA-n-2017>[https://www.fda.gov/drugs/developmentapprovalprocess/druginnovation/ucm537040.htm Novel Drug Approvals for 2017] {{webarchive|url=https://web.archive.org/web/20170629124028/https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm537040.htm |date=29 June 2017 }}</ref> There have been few studies of the efficacy of anti-TNF medications for psoriasis in children. One randomized control study suggested that 12 weeks of etanercept treatment reduced the extent of psoriasis in children with no lasting adverse effects.<ref>{{cite journal | vauthors = Sanclemente G, Murphy R, Contreras J, García H, Bonfill Cosp X | title = Anti-TNF agents for paediatric psoriasis | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD010017 | date = November 2015 | volume = 2019 | pmid = 26598969 | pmc = 6493213 | doi = 10.1002/14651858.CD010017.pub2 }}</ref>

<!-- Others -->
Two medications that target T cells are [[efalizumab]] and [[alefacept]]. Efalizumab is a monoclonal antibody that specifically targets the [[CD11a]] subunit of [[LFA-1]].<ref name="Rustin2012"/> It also blocks the adhesion molecules on the [[endothelial]] cells that line blood vessels, which attract T cells. Efalizumab was voluntarily withdrawn from the European market in February 2009, and from the U.S. market in June 2009, by the manufacturer due to the medication's association with cases of [[progressive multifocal leukoencephalopathy]].<ref name="Rustin2012"/> Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causes [[natural killer cell]]s to kill T cells as a way of controlling inflammation.<ref name=Nestle/> [[Apremilast]] may also be used.<ref name="Palfreeman2013"/>

Individuals with psoriasis may develop [[neutralizing antibodies]] against monoclonal antibodies. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody such as infliximab from binding [[antigen]] in a laboratory test. Specifically, neutralization occurs when the anti-drug antibody binds to infliximab's antigen binding site instead of TNF-α. When infliximab no longer binds [[tumor necrosis factor alpha]], it no longer decreases inflammation, and psoriasis may worsen. Neutralizing antibodies have not been reported against [[etanercept]], a biologic medication that is a fusion protein composed of two TNF-α receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor, and the development of [[immune tolerance]].<ref>{{cite journal | vauthors = Harding FA, Stickler MM, Razo J, DuBridge RB | title = The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions | journal = mAbs | volume = 2 | issue = 3 | pages = 256–65 | date = 2010 | pmid = 20400861 | pmc = 2881252 | doi = 10.4161/mabs.2.3.11641 }}</ref>

There is strong evidence to indicate that infliximab, [[bimekizumab]], ixekizumab, and [[risankizumab]] are the most effective biologics for treating moderate to severe cases of psoriasis.<ref name=":5">{{cite journal | vauthors = Sbidian E, Chaimani A, Guelimi R, Garcia-Doval I, Hua C, Hughes C, Naldi L, Kinberger M, Afach S, Le Cleach L | title = Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 7 | pages = CD011535 | date = July 2023 | pmid = 37436070 | pmc = 10337265 | doi = 10.1002/14651858.CD011535.pub6 }}</ref> There is also some evidence to support use of [[secukinumab]], [[brodalumab]], [[guselkumab]], certolizumab, and ustekinumab.<ref name="pmid26714681">{{cite journal | vauthors = Campa M, Mansouri B, Warren R, Menter A | title = A Review of Biologic Therapies Targeting IL-23 and IL-17 for Use in Moderate-to-Severe Plaque Psoriasis | journal = Dermatology and Therapy | volume = 6 | issue = 1 | pages = 1–12 | date = March 2016 | pmid = 26714681 | pmc = 4799039 | doi = 10.1007/s13555-015-0092-3 }}</ref><ref name=":5" /> In general, anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha biologics were found to be more effective than traditional systemic treatments.<ref name=":5" /> The [[Immunology|immunologic]] pathways of psoriasis involve [[Th 9 cell|Th9]], [[Th17]], [[Th1 cell|Th1]] lymphocytes, and [[Interleukin 22|IL-22]]. The aforementioned biologic agents hinder different aspects of these pathways.{{citation needed|date=January 2020}}

Another set of treatments for moderate to severe psoriasis are [[fumaric acid esters]] (FAE), which may be similar in effectiveness to [[methotrexate]].<ref>{{cite journal | vauthors = Atwan A, Ingram JR, Abbott R, Kelson MJ, Pickles T, Bauer A, Piguet V | title = Oral fumaric acid esters for psoriasis | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 8 | pages = CD010497 | date = August 2015 | pmid = 26258748 | pmc = 6464505 | doi = 10.1002/14651858.CD010497.pub2 }}</ref>

[[Apremilast]] (Otezla, Celgene) is an oral small-molecule inhibitor of the enzyme [[phosphodiesterase 4]], which plays an important role in chronic inflammation associated with psoriasis.<ref>{{cite journal |last1=Papp |first1=K |last2=Reich |first2=K |last3=Leonardi |first3=CL |last4=Kircik |first4=L |last5=Chimenti |first5=S |last6=Langley |first6=RG |last7=Hu |first7=C |last8=Stevens |first8=RM |last9=Day |first9=RM |last10=Gordon |first10=KB |last11=Korman |first11=NJ |last12=Griffiths |first12=CE |title=Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). |journal=Journal of the American Academy of Dermatology |date=July 2015 |volume=73 |issue=1 |pages=37–49 |doi=10.1016/j.jaad.2015.03.049 |pmid=26089047 |url=https://pubmed.ncbi.nlm.nih.gov/26089047/ |access-date=17 September 2024|doi-access=free }}</ref>

It has been theorized that [[Streptococcus|antistreptococcal]] medications may improve guttate and chronic plaque psoriasis; however, limited studies do not show that [[antibiotic]]s are effective.<ref>{{cite journal | vauthors = Dupire G, Droitcourt C, Hughes C, Le Cleach L | title = Antistreptococcal interventions for guttate and chronic plaque psoriasis | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD011571 | date = March 2019 | issue = 3 | pmid = 30835819 | pmc = 6400423 | doi = 10.1002/14651858.cd011571.pub2 }}</ref>