{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:06:26Z","timestamp":1790751986718,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phosphodiesterases (PDEs) are a heterogeneous superfamily of enzymes which catalyze the degradation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Among PDEs, PDE4 is the most widely studied and characterized isoenzyme. PDE4 blocking can lead to increased levels of intracellular cAMP, which results in down-regulation of inflammatory responses by reducing the expression of tumor necrosis factor (TNF), interleukin (IL)-23, IL-17, interferon-\u03b3, while increasing regulatory cytokines, such as IL-10. Therefore, PDE4 has been explored as a therapeutic target for the treatment of different chronic inflammatory conditions such as psoriatic arthritis (PsA) and inflammatory bowel disease (IBD). PsA shares clinical, genetic, and pathogenic features with IBD such as ulcerative colitis (UC) and Crohn\u2019s disease (CD), and enteropathic spondyloarthritis (eSpA) represent a frequent clinical evidence of the overlap between gut and joint diseases. Current therapeutic options in PsA patients and underlying UC are limited to synthetic immunosuppressants and anti-TNF. Apremilast is an oral PDE4 inhibitor approved for the treatment of active PsA patients with inadequate response to synthetic immunosuppressants. The efficacy and a good safety profile observed in randomized clinical trials with apremilast in PsA patients have been confirmed by few studies in a real-life scenario. In addition, apremilast led to significant improvement in clinical and endoscopic features in UC patients in a phase II RCT. By now there are no available data regarding its role in eSpA patients. In view of the above, the use of apremilast in eSpA patients is a route that deserves to be deepened.<\/jats:p>","DOI":"10.3390\/ijms22052638","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T11:46:09Z","timestamp":1614944769000},"page":"2638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Inhibition of Phosphodiesterase-4 in Psoriatic Arthritis and Inflammatory Bowel Diseases"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-4641","authenticated-orcid":false,"given":"Andrea","family":"Picchianti-Diamanti","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, S. Andrea University Hospital, \u201cSapienza\u201d University, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Romana","family":"Spinelli","sequence":"additional","affiliation":[{"name":"Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, \u201cSapienza\u201d Universit\u00e0 di Roma, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Manuela","family":"Rosado","sequence":"additional","affiliation":[{"name":"Consultant in Immunology, 00125 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-049X","authenticated-orcid":false,"given":"Fabrizio","family":"Conti","sequence":"additional","affiliation":[{"name":"Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, \u201cSapienza\u201d Universit\u00e0 di Roma, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2305-4063","authenticated-orcid":false,"given":"Bruno","family":"Lagan\u00e0","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, S. Andrea University Hospital, \u201cSapienza\u201d University, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/0006-291X(63)90566-7","article-title":"Isolation of adenosine 3\u2019, 5\u2019-monophosphate and guanosine 3\u2019, 5\u2019-monophosphate from rat urine","volume":"11","author":"Ashman","year":"1963","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1124\/mol.104.009423","article-title":"Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene","volume":"67","author":"Wallace","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1152\/physrev.1995.75.4.725","article-title":"Cyclic nucleotide phosphodiesterases: Functional implications of multiple isoforms","volume":"75","author":"Beavo","year":"1995","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1111\/odi.12275","article-title":"Cyclic nucleotide phosphodiesterases: Important signaling modulators and therapeutic targets","volume":"21","author":"Ahmad","year":"2015","journal-title":"Oral Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev.med.60.051407.123757","article-title":"IL-23 and autoimmunity: New insights into the pathogenesis of inflammatory bowel disease","volume":"60","author":"Abraham","year":"2009","journal-title":"Annu. Rev. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1046\/j.1365-2133.2002.04742.x","article-title":"Quality of life in 6497 Nordic patients with psoriasis","volume":"146","author":"Zachariae","year":"2002","journal-title":"Br. J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1053\/gast.1996.v110.pm8964393","article-title":"Long-term evolution of gut inflammation in patients with spondyloarthropathy","volume":"110","author":"Mielants","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.autrev.2014.04.003","article-title":"Italian Expert Panel on the management of patients with coexisting spondyloarthritis and inflammatory bowel disease","volume":"13","author":"Olivieri","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_9","first-page":"2279","article-title":"The evolution of spondyloarthropathies in relation to gut histology. III. Relation between gut and joint","volume":"22","author":"Mielants","year":"1995","journal-title":"J. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102457","DOI":"10.1016\/j.autrev.2019.102457","article-title":"Enteropathic spondyloarthritis: Results from a large nationwide database analysis","volume":"19","author":"Lorenzetti","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1080\/03007995.2020.1786681","article-title":"Safety profiles of biologic agents for inflammatory bowel diseases: A prospective pharmacovigilance study in Southern Italy","volume":"36","author":"Roberti","year":"2020","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Iannone, L.F., Bennardo, L., Palleria, C., Roberti, R., De Sarro, C., Naturale, M.D., Dastoli, S., Donato, L., Manti, A., and Valenti, G. (2020). Safety profile of biologic drugs for psoriasis in clinical practice: An Italian prospective pharmacovigilance study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241575"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1093\/rheumatology\/kes170","article-title":"Increased expression of interleukin-32 in the inflamed ileum of ankylosing spondylitis patients","volume":"51","author":"Ciccia","year":"2012","journal-title":"Rheumatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e321","DOI":"10.1111\/bjd.15533","article-title":"Interleukin (IL)-17A and IL-22-producing neutrophils in psoriatic skin","volume":"177","author":"Honore","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/BOR.0000000000000569","article-title":"The ties that bind: Skin, gut and spondyloarthritis","volume":"31","author":"Gracey","year":"2019","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"589726","DOI":"10.3389\/fmicb.2020.589726","article-title":"Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies","volume":"11","author":"Chen","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Picchianti-Diamanti, A., Panebianco, C., Salemi, S., Sorgi, M.L., Di Rosa, R., Tropea, A., Sgrulletti, M., Salerno, G., Terracciano, F., and D\u2019Amelio, R. (2018). Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102938"},{"key":"ref_18","first-page":"2696","article-title":"Infectious Agents and Inflammation: The Role of Microbiota in Autoimmune Arthritis","volume":"8","author":"Rosado","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101494","DOI":"10.1016\/j.berh.2020.101494","article-title":"The gut microbiome in psoriasis and psoriatic arthritis","volume":"33","author":"Myers","year":"2019","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/art.38892","article-title":"Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease","volume":"67","author":"Scher","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1136\/annrheumdis-2020-217159","article-title":"EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update","volume":"79","author":"Gossec","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/ecco-jcc\/jjv213","article-title":"The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease","volume":"10","author":"Harbord","year":"2016","journal-title":"J. Crohns Colitis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/j.bcp.2012.01.001","article-title":"Apremilast mechanism of action and application to psoriasis and psoriatic arthritis","volume":"83","author":"Schafer","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1136\/annrheumdis-2015-207963","article-title":"Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: A phase III, randomised, controlled trial (PALACE 3)","volume":"75","author":"Edwards","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1093\/rheumatology\/key032","article-title":"Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: Results of the randomized, placebo-controlled PALACE 4 trial","volume":"57","author":"Wells","year":"2018","journal-title":"Rheumatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.3899\/jrheum.151376","article-title":"A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial","volume":"43","author":"Cutolo","year":"2016","journal-title":"J. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/annrheumdis-2013-205056","article-title":"Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor","volume":"73","author":"Kavanaugh","year":"2014","journal-title":"Ann. Rheum Dis."},{"key":"ref_28","unstructured":"Otezla, INN-apremilast-europa.eu (2021, February 21). Available online: www.ema.europa.eu&gt;otezla-epar-product-information_it."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1016\/j.cgh.2019.12.032","article-title":"Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis","volume":"18","author":"Danese","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.4049\/jimmunol.137.10.3299","article-title":"Antibody binding to CD5 (Tp67) and Tp44 T cell surface molecules: Effects on cyclic nucleotides, cytoplasmic free calcium, and cAMP-mediated suppression","volume":"137","author":"Ledbetter","year":"1986","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/73144","article-title":"p27kip1 functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes","volume":"6","author":"Boussiotis","year":"2000","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1006\/cimm.1996.0274","article-title":"Elevation of intracellular cyclic AMP induces an anergic-like state in Th1 clones","volume":"173","author":"Cone","year":"1996","journal-title":"Cell Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4847","DOI":"10.4049\/jimmunol.173.8.4847","article-title":"TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling","volume":"173","author":"Abrahamsen","year":"2004","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1126\/science.283.5403.848","article-title":"CD3- and CD28-dependent induction of PDE7 required for T cell activation","volume":"283","author":"Li","year":"1999","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1111\/j.1476-5381.1996.tb15629.x","article-title":"Identification of cyclic AMP phosphodiesterases 3, 4 and 7 in human CD4+ and CD8+ T-lymphocytes: Role in regulating proliferation and the biosynthesis of interleukin-2","volume":"118","author":"Giembycz","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/bph.12308","article-title":"Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis","volume":"170","author":"Bravo","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S1359-6446(05)03622-6","article-title":"Keynote review: Phosphodiesterase-4 as a therapeutic target","volume":"10","author":"Houslay","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0014-2999(96)00357-3","article-title":"Selective inhibition of phosphodiesterase type IV suppresses the chemotactic responsiveness of rat eosinophils in vitro","volume":"312","author":"Alves","year":"1996","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.pupt.2004.10.001","article-title":"The effect of selective phosphodiesterase isoenzyme inhibition on neutrophil function in vitro","volume":"18","author":"Jones","year":"2005","journal-title":"Pulm Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1016\/j.cellsig.2014.05.014","article-title":"Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity","volume":"26","author":"Schafer","year":"2014","journal-title":"Cell Signal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/jlb.63.1.101","article-title":"Anti-inflammatory activities of cAMP-elevating agents: Enhancement of IL-10 synthesis and concurrent suppression of TNF production","volume":"63","author":"Eigler","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1002\/(SICI)1521-4141(199910)29:10<3098::AID-IMMU3098>3.0.CO;2-H","article-title":"Cyclic adenosine monophosphate-responsive elements are involved in the transcriptional activation of the human IL-10 gene in monocytic cells","volume":"29","author":"Platzer","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0091-6749(97)70297-5","article-title":"Differential efficacy of lymphocyte- and monocyte-selective pretreatment with a type 4 phosphodiesterase inhibitor on antigen-driven proliferation and cytokine gene expression","volume":"99","author":"Essayan","year":"1997","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4017","DOI":"10.4049\/jimmunol.0803310","article-title":"Inhibition of cAMP degradation improves regulatory T cell-mediated suppression","volume":"182","author":"Bopp","year":"2009","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.intimp.2008.05.012","article-title":"A selective phosphodiesterase 4 (PDE4) inhibitor Zl-n-91 suppresses IL-17 production by human memory Th17 cells","volume":"8","author":"Ma","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1038\/sj.bjp.0704644","article-title":"Rolipram inhibits leukocyte-endothelial cell interactions in vivo through P- and E-selectin downregulation","volume":"135","author":"Sanz","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1160\/TH03-02-0084","article-title":"VEGF-induced HUVEC migration and proliferation are decreased by PDE2 and PDE4 inhibitors","volume":"90","author":"Favot","year":"2003","journal-title":"Thromb. Haemost."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1124\/mol.104.004853","article-title":"Vascular endothelial cell cyclic nucleotide phosphodiesterases and regulated cell migration: Implications in angiogenesis","volume":"67","author":"Netherton","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Spadaccini, M., D\u2019Alessio, S., Peyrin-Biroulet, L., and Danese, S. (2017). PDE4 Inhibition and Inflammatory Bowel Disease: A Novel Therapeutic Avenue. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061276"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.crohns.2009.03.001","article-title":"CC-10004 but not thalidomide or lenalidomide inhibits lamina propria mononuclear cell TNF-alpha and MMP-3 production in patients with inflammatory bowel disease","volume":"3","author":"Gordon","year":"2009","journal-title":"J. Crohns Colitis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1111\/bph.14667","article-title":"Inhibition of phosphodiesterase-4 attenuates murine ulcerative colitis through interference with mucosal immunity","volume":"176","author":"Li","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"906349","DOI":"10.1155\/2015\/906349","article-title":"The pharmacodynamic impact of apremilast, an oral phosphodiesterase 4 inhibitor, on circulating levels of inflammatory biomarkers in patients with psoriatic arthritis: Substudy results from a phase III, randomized, placebo-controlled trial (PALACE 1)","volume":"2015","author":"Schafer","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.3389\/fimmu.2018.01662","article-title":"Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of CD4(+)Foxp3(+) Regulatory T Cells Differentiation","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1093\/rheumatology\/kez204","article-title":"Apremilast increases IL-10-producing regulatory B cells and decreases proinflammatory T cells and innate cells in psoriatic arthritis and psoriasis","volume":"58","author":"Mavropoulos","year":"2019","journal-title":"Rheumatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R107","DOI":"10.1186\/ar3041","article-title":"Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis","volume":"12","author":"McCann","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s13075-015-0771-6","article-title":"Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors","volume":"17","author":"Montesinos","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1759720X19828669","DOI":"10.1177\/1759720X19828669","article-title":"IL-12\/IL-23p40 identified as a downstream target of apremilast in ex vivo models of arthritis","volume":"11","author":"Kragstrup","year":"2019","journal-title":"Ther. Adv. Musculoskelet Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13075-019-1901-3","article-title":"Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis","volume":"21","author":"Kavanaugh","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/acr2.11156","article-title":"Long-Term Safety and Tolerability of Apremilast Versus Placebo in Psoriatic Arthritis: A Pooled Safety Analysis of Three Phase III, Randomized, Controlled Trials","volume":"2","author":"Mease","year":"2020","journal-title":"ACR Open Rheumatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1136\/annrheumdis-2017-211568","article-title":"Early and sustained efficacy with apremilast monotherapy in biological-na\u00efve patients with psoriatic arthritis: A phase IIIB, randomised controlled trial (ACTIVE)","volume":"77","author":"Nash","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e000669","DOI":"10.1136\/rmdopen-2018-000669","article-title":"Therapeutic benefit of apremilast on enthesitis and dactylitis in patients with psoriatic arthritis: A pooled analysis of the PALACE 1\u20133 studies","volume":"4","author":"Gladman","year":"2018","journal-title":"RMD Open"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/rheumatology\/kex454","article-title":"Apremilast for the treatment of active psoriatic arthritis: A single-centre real-life experience","volume":"57","author":"Abignano","year":"2018","journal-title":"Rheumatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1016\/j.jaad.2019.02.014","article-title":"A comparison of apremilast monotherapy and combination therapy for psoriatic arthritis in a real-life setting: Data from the Leeds Combined Psoriatic Service","volume":"80","author":"Abignano","year":"2019","journal-title":"J. Am. Acad Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"234","DOI":"10.2174\/1573397115666181130094455","article-title":"Combination Therapy of Apremilast and Biologic Agent as a Safe Option of Psoriatic Arthritis and Psoriasis","volume":"15","author":"Metyas","year":"2019","journal-title":"Curr. Rheumatol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ogdie, A., Liu, M., Glynn, M., Emeanuru, K., Harrold, L., Richter, S., Guerette, B., and Mease, P.J. (2020). Descriptive Comparisons of the Impact of Apremilast and Methotrexate Monotherapy in Oligoarticular Psoriatic Arthritis: The Corrona Psoriatic Arthritis\/Spondyloarthritis Registry Results. J. Rheumatol.","DOI":"10.1136\/annrheumdis-2019-eular.779"},{"key":"ref_66","first-page":"19","article-title":"Retrospective evaluation of patient profiling and effectiveness of apremilast in an Italian multicentric cohort of psoriatic arthritis patients","volume":"38","author":"Favalli","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1093\/rheumatology\/key145","article-title":"Early response to apremilast treatment in psoriatic arthritis: A real-life ultrasonographic follow-up study","volume":"57","author":"Ceccarelli","year":"2018","journal-title":"Rheumatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1007\/s10067-019-04674-3","article-title":"Musculoskeletal ultrasound in monitoring response to apremilast in psoriatic arthritis patients: Results from a longitudinal study","volume":"38","author":"Ceccarelli","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e13440","DOI":"10.1111\/dth.13440","article-title":"Long-term efficacy and safety of apremilast in psoriatic arthritis: Focus on skin manifestations and special populations","volume":"33","author":"Balato","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2147\/CLEP.S239511","article-title":"Herpes Zoster, Hepatitis C, and Tuberculosis Risk with Apremilast Compared to Biologics, Dmards and Corticosteroids to Treat Psoriasis and Psoriatic Arthritis","volume":"12","author":"Hagberg","year":"2020","journal-title":"Clin. Epidemiol."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/cei.13451","article-title":"Serum sCD40L levels are increased in patients with psoriatic arthritis and are associated with clinical response to apremilast","volume":"201","author":"Venerito","year":"2020","journal-title":"Clin. Exp. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"699","DOI":"10.2217\/cer-2019-0034","article-title":"Treatment patterns and costs among biologic-naive patients initiating apremilast or biologics for psoriatic arthritis","volume":"8","author":"Feldman","year":"2019","journal-title":"J. Comp. Eff. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1111\/1346-8138.14617","article-title":"Real-world use of apremilast for patients with psoriasis in Japan","volume":"45","author":"Kishimoto","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2217\/cer-2018-0097","article-title":"Real-world US healthcare costs of psoriasis for biologic-naive patients initiating apremilast or biologics","volume":"8","author":"Feldman","year":"2019","journal-title":"J. Comp. Eff. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"767","DOI":"10.2217\/cer-2020-0045","article-title":"Real-world switch patterns and healthcare costs in biologic-naive psoriasis patients initiating apremilast or biologics","volume":"9","author":"Wu","year":"2020","journal-title":"J. Comp. Eff. Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Persson, R., Hagberg, K.W., Qian, Y., Vasilakis-Scaramozza, C., and Jick, S. (2020). The risks of major cardiac events among patients with psoriatic arthritis treated with apremilast, biologics, DMARDs or corticosteroids. Rheumatology.","DOI":"10.1093\/rheumatology\/keaa683"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2638\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:33:47Z","timestamp":1760160827000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":77,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22052638"],"URL":"https:\/\/doi.org\/10.3390\/ijms22052638","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]}}}