{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:13:38Z","timestamp":1792700018382,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/genes12091398","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T10:31:34Z","timestamp":1631269894000},"page":"1398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Pharmacogenomics: An Update on Biologics and Small-Molecule Drugs in the Treatment of Psoriasis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3503-3318","authenticated-orcid":false,"given":"Valerio","family":"Caputo","sequence":"first","affiliation":[{"name":"Medical Genetics Laboratory, Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy"},{"name":"Genomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1334-0920","authenticated-orcid":false,"given":"Claudia","family":"Strafella","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy"},{"name":"Genomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4025-7882","authenticated-orcid":false,"given":"Terenzio","family":"Cosio","sequence":"additional","affiliation":[{"name":"Dermatologic Unit, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Lanna","sequence":"additional","affiliation":[{"name":"Dermatologic Unit, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Campione","sequence":"additional","affiliation":[{"name":"Dermatologic Unit, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-602X","authenticated-orcid":false,"given":"Giuseppe","family":"Novelli","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Department of Pharmacology, School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Giardina","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy"},{"name":"Genomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Cascella","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy"},{"name":"Department of Biomedical Sciences, Catholic University Our Lady of Good Counsel, 1000 Tirana, Albania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3389\/fphys.2015.00364","article-title":"Forward individualized medicine from personal genomes to interactomes","volume":"6","author":"Zhang","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"314","DOI":"10.2174\/138920212800793311","article-title":"The pharmacogenomic HLA biomarker associated to adverse abacavir reactions: Comparative analysis of different genotyping methods","volume":"13","author":"Stocchi","year":"2012","journal-title":"Curr. Genom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/tpj.2014.48","article-title":"Direct PCR: A new pharmacogenetic approach for the inexpensive testing of HLA-B*57:01","volume":"15","author":"Cascella","year":"2014","journal-title":"Pharmacogenom. J."},{"key":"ref_4","first-page":"467","article-title":"Pharmacogenomics and individualized medicine: Translating science into practice","volume":"92","author":"Crews","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41397-019-0123-z","article-title":"Pharmacogenomic biomarker information differences between drug labels in the United States and Hungary: Implementation from medical practitioner view","volume":"20","author":"Varnai","year":"2020","journal-title":"Pharmacogenom. J."},{"key":"ref_6","first-page":"197","article-title":"Pharmacogenetics in inflammatory bowel disease: Understanding treatment response and personalizing therapeutic strategies","volume":"10","year":"2017","journal-title":"Pharmgenom. Pers. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"D\u00e1vila-Fajardo, C.L., D\u00edaz-Villamar\u00edn, X., Ant\u00fanez-Rodr\u00edguez, A., Fern\u00e1ndez-G\u00f3mez, A.E., Garc\u00eda-Navas, P., Mart\u00ednez-Gonz\u00e1lez, L.J., D\u00e1vila-Fajardo, J.A., and Barrera, J.C. (2019). Pharmacogenetics in the Treatment of Cardiovascular Diseases and Its Current Progress Regarding Implementation in the Clinical Routine. Genes, 10.","DOI":"10.3390\/genes10040261"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40364-020-00213-4","article-title":"Application of pharmacogenetics in oncology","volume":"8","author":"Ivanov","year":"2020","journal-title":"Biomark. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1080\/17425255.2016.1194394","article-title":"Pharmacogenetics and pharmacogenomics in psoriasis treatment: Current challenges and future prospects","volume":"12","author":"Sutherland","year":"2016","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13146","DOI":"10.3748\/wjg.v20.i36.13146","article-title":"IL28B polymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients","volume":"20","author":"Rosso","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0140-6736(02)08158-8","article-title":"Genetic variations in HLA-B region and hypersensitivity reactions to abacavir","volume":"358","author":"Hetherington","year":"2002","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13554","DOI":"10.1111\/jcmm.15742","article-title":"Overview of the molecular determinants contributing to the expression of Psoriasis and Psoriatic Arthritis phenotypes","volume":"24","author":"Caputo","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.7861\/clinmedicine.17-1-65","article-title":"Psoriatic arthritis: State of the art review","volume":"17","author":"Coates","year":"2017","journal-title":"Clin. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"95401","DOI":"10.18632\/oncotarget.20727","article-title":"KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility","volume":"8","author":"Cascella","year":"2017","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.7861\/clinmed.2021-0257","article-title":"Psoriasis: A brief overview","volume":"21","author":"Raharja","year":"2021","journal-title":"Clin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/1346-8138.15293","article-title":"Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers","volume":"47","author":"Mazzilli","year":"2020","journal-title":"J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Caputo, V., Strafella, C., Termine, A., Campione, E., Bianchi, L., Novelli, G., Giardina, E., and Cascella, R. (2020). RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082740"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1038\/jid.2010.88","article-title":"Deletion of Late Cornified Envelope 3B and 3C genes is not associated with atopic dermatitis","volume":"130","author":"Bergboer","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1159\/000095059","article-title":"Co-localization of susceptibility loci for psoriasis (PSORS4) and atopic dermatitis (ATOD2) on human chromosome 1q21","volume":"61","author":"Giardina","year":"2006","journal-title":"Hum. Hered."},{"key":"ref_20","first-page":"65","article-title":"GRAPPA Treatment Recommendations: An Update from the 2020 GRAPPA Annual Meeting","volume":"97","author":"Coates","year":"2021","journal-title":"J. Rheumatol. Suppl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1136\/annrheumdis-2021-220202","article-title":"Primary and secondary non-response: In need of operational definitions in observational studies","volume":"80","author":"Keystone","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/jdv.16980","article-title":"Immunogenicity of biologic therapies in psoriasis: Myths, facts and a suggested approach","volume":"35","author":"Tsakok","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1136\/postgradmedj-2015-133419","article-title":"TNF-\u03b1 in a molecularly targeted therapy of psoriasis and psoriatic arthritis","volume":"92","author":"Mazurek","year":"2016","journal-title":"Postgrad. Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.2217\/pgs.13.163","article-title":"Pharmacogenetics of topical and systemic treatment of psoriasis","volume":"14","author":"Cabaleiro","year":"2013","journal-title":"Pharmacogenomics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1084\/jem.20031482","article-title":"Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-\u03b1","volume":"199","author":"Boyman","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s40257-017-0322-9","article-title":"Pharmacogenetics and Pharmacogenomics in Moderate-to-Severe Psoriasis","volume":"19","author":"Reolid","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/tpj.2015.53","article-title":"Paradoxical psoriasiform reactions to anti-TNF drugs are associated with genetic polymorphisms in patients with psoriasis","volume":"16","author":"Cabaleiro","year":"2016","journal-title":"Pharmacogenom. J."},{"key":"ref_28","first-page":"169","article-title":"Psoriasis Induced by Anti-Tumor Necrosis Factor \u03b1 Agents: A Comprehensive Review of the Literature","volume":"24","author":"Ciccarelli","year":"2016","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Aceituno, E., Martos-Cabrera, L., Ovejero-Benito, M.C., Reolid, A., Abad-Santos, F., and Daud\u00e9n, E. (2020). Pharmacogenetics Update on Biologic Therapy in Psoriasis. Medicina, 56.","DOI":"10.3390\/medicina56120719"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1159\/000502255","article-title":"A meta-analysis of the relationship between tumor necrosis factor-\u03b1 polymorphisms and psoriasis","volume":"237","author":"Wang","year":"2021","journal-title":"Dermatology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Membrive Jim\u00e9nez, C., P\u00e9rez Ram\u00edrez, C., S\u00e1nchez Mart\u00edn, A., Vieira Maroun, S., Arias Santiago, S.A., Ram\u00edrez Tortosa, M.D.C., and Jim\u00e9nez Morales, A. (2021). Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11040293"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.2217\/pgs.15.90","article-title":"Association between TNF-\u03b1 (-308 A\/G, -238 A\/G, -857 C\/T) polymorphisms and responsiveness to TNF-\u03b1 blockers in spondyloarthropathy, psoriasis and Crohn\u2019s disease: A meta-analysis","volume":"16","author":"Song","year":"2015","journal-title":"Pharmacogenomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100096","DOI":"10.1016\/j.jtauto.2021.100096","article-title":"Predicted regulatory SNPs reveal potential drug targets and novel companion diagnostics in psoriasis","volume":"4","year":"2021","journal-title":"J. Transl. Autoimmun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1111\/exd.14215","article-title":"Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs","volume":"29","author":"Sabador","year":"2020","journal-title":"Exp. Dermatol."},{"key":"ref_35","first-page":"39","article-title":"Biologic Treatments of Psoriasis: An Update for the Clinician","volume":"15","author":"Brownstone","year":"2021","journal-title":"Biologics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/ijd.14695","article-title":"IL-17 and its role in inflammatory, autoimmune, and oncological skin diseases: State of art","volume":"59","author":"Bernardini","year":"2020","journal-title":"Int. J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2147\/JIR.S100940","article-title":"Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A","volume":"9","author":"Liu","year":"2016","journal-title":"J. Inflamm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jaad.2016.08.008","article-title":"Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study","volume":"76","author":"Blauvelt","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nri1745","article-title":"Dectin-1: A signalling non-TLR pattern-recognition receptor","volume":"6","author":"Brown","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jphs.2020.06.003","article-title":"Predictive role of vitamin A serum concentration in psoriatic patients treated with IL-17 inhibitors to prevent skin and systemic fungal infections","volume":"144","author":"Campione","year":"2020","journal-title":"J. Pharmacol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/jdv.15787","article-title":"Response to IL-17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein-coding and untranslated regions of the IL-17A gene: Results from a multicentre study of four European psoriasis cohorts","volume":"34","author":"Meulewaeter","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1111\/bjd.16705","article-title":"Secukinumab shows high efficacy irrespective of HLA-Cw6 status in patients with moderate-to-severe plaque-type psoriasis: SUPREME study","volume":"79","author":"Costanzo","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00403-019-02011-x","article-title":"A potential association between psoriasin to rs4819554 of IL-17RA gene polymorphism in psoriasis Egyptian patients","volume":"312","author":"Sabry","year":"2020","journal-title":"Arch. Dermatol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s40291-018-0354-8","article-title":"Treating a Multidrug-Resistant Psoriatic HLA-C*18:01 Allele Carrier with Combination Ustekinumab Apremilast Therapy","volume":"22","author":"Galluzzo","year":"2018","journal-title":"Mol. Diagn. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/idoj.IDOJ_437_18","article-title":"Apremilast in Psoriasis and Beyond: Big Hopes on a Small Molecule","volume":"10","author":"Afra","year":"2019","journal-title":"Indian Dermatol. Online J."},{"key":"ref_46","first-page":"1080","article-title":"Use of brodalumab for the treatment of chronic plaque psoriasis: A one-year real-life study in the Lazio region, Italy","volume":"10","author":"Galluzzo","year":"2021","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.jaad.2020.11.013","article-title":"Brodalumab success in patients with moderate-to-severe psoriasis who failed previous interleukin-17A inhibitors","volume":"84","author":"Yeung","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3389\/fphar.2018.01048","article-title":"Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases","volume":"9","author":"Li","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1586\/1744666X.2016.1134319","article-title":"A new therapeutic for the treatment of moderate-to-severe plaque psoriasis: Apremilast","volume":"12","author":"Chiricozzi","year":"2016","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1080\/14656566.2021.1939307","article-title":"An evaluation of apremilast for the treatment of adult patients with oral ulcers associated with Beh\u00e7et\u2019s syndrome","volume":"22","author":"Hatemi","year":"2021","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Verbenko, D.A., Karamova, A.E., Artamonova, O.G., Deryabin, D.G., Rakitko, A., Chernitsov, A., Krasnenko, A., Elmuratov, A., Solomka, V.S., and Kubanov, A.A. (2020). Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11010020"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/14740338.2020.1736553","article-title":"A safety evaluation of dimethyl fumarate in moderate-to-severe psoriasis","volume":"19","author":"Reszke","year":"2020","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1177\/0300060519847414","article-title":"Efficacy and safety of tofacitinib for the treatment of chronic plaque psoriasis: A systematic review and meta-analysis","volume":"47","author":"Tian","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"943","DOI":"10.2217\/pgs.16.20","article-title":"Pharmacogenomics of multifactorial diseases: A focus on psoriatic arthritis","volume":"17","author":"Cascella","year":"2016","journal-title":"Pharmacogenomics"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/9\/1398\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:00:10Z","timestamp":1760166010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/9\/1398"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,10]]},"references-count":54,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["genes12091398"],"URL":"https:\/\/doi.org\/10.3390\/genes12091398","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,10]]}}}