title: Novel Oral Therapies for Psoriasis and Psoriatic Arthritis.
abstract: Several classes of new oral therapy are in use or in development for the treatment of psoriasis. Despite the high efficacy of biologics, new oral therapies remain important as patients generally prefer this mode of administration and they offer an alternative risk-benefit profile. In this review, we discuss the novel modes of action of these drugs, including modulation of cellular pathways involving diverse targets such as Janus kinase, phosphodiesterase 4, sphingosine 1-phosphate, A3 adenosine receptor and rho-associated kinase 2. We review the available evidence around licensed drugs (apremilast) and drugs that are advanced (tofacitinib) or early (ponesimod, baricitinib, peficitinib, INCB039110, CF101, KD025) in the development pipeline. The key limitations of these oral therapies are their modest efficacy profile (apremilast, ponesimod) and the limitations of their safety profile (tofacitinib, ponesimod), while the evidence for the early pipeline drugs are at phase II level only. Potential niches of current unmet needs include apremilast for patients with concomitant psoriatic arthritis, as combination treatments with biologic therapies, and/or for patients in whom multiple biologic therapies have failed due to immunogenicity and secondary inefficacy. The present knowledge gap regarding these novel drugs includes the need for longer clinical trials or observational studies to evaluate safety, and randomised phase III trials for the early pipeline drugs. We conclude that further research and data are necessary to conclusively establish the role of these agents in the current psoriasis treatment paradigm.
authors.affiliation: Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, M6 8HD, UK. zenas.yiu@manchester.ac.uk.
authors.forename: Zenas Z N
authors.initials: ZZ
authors.lastname: Yiu
authors.affiliation: Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, M6 8HD, UK. richard.warren@manchester.ac.uk.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Warren
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D058918:Adenosine A3 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000284:Administration, Oral; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001685:Biological Factors / Q000627:therapeutic use; D001691:Biological Therapy; D002986:Clinical Trials as Topic; D006801:Humans; D007539:Isonicotinic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy*; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D001384:Azetidines; D001685:Biological Factors; C478920:CF101; C000603457:INCB039110; D007539:Isonicotinic Acids; D058988:Phosphodiesterase 4 Inhibitors; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; D011758:Pyrroles; D049349:Receptors, Lysosphingolipid; D013449:Sulfonamides; D013844:Thiazoles; D009536:Niacinamide; D013792:Thalidomide; C550169:ponesimod; C479163:tofacitinib; D053612:Janus Kinases; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; C000608065:peficitinib; C000596027:baricitinib; D000241:Adenosine; D000218:Adamantane; C505730:apremilast