Novel biologic therapies in development targeting IL-12/IL-23.
Recent research has identified the importance of interleukin 12 (IL)-12 and IL-23 in the immunopathogenesis of psoriasis. The p40 subunit common to IL-12 and IL-23 is an attractive target for selective therapy. Clinical study data are available for two anti-IL-12/23 therapies: ustekinumab (CNTO 1275, approved in 2009 for treatment of plaque psoriasis) and ABT-874. The Phase 3 clinical trials PHOENIX 1 and PHOENIX 2 have shown significant benefit for ustekinumab in moderate-to-severe plaque psoriasis, with PASI 75 response rates ranging from 66% at week 12 (after two injections) and rising to 85% at week 24 (after three injections). Withdrawal of treatment led to a gradual return of psoriasis whereas continued therapy every 12 weeks with ustekinumab maintained PASI 75 response. Analysis of safety data demonstrated a safety profile similar to placebo at week 12 and did not reveal any major safety concerns in blocking IL-12 and IL-23 for periods as long as 18 months. Phase 2 data indicate that ABT-874 is also efficacious in the treatment of moderate-to-severe plaque psoriasis across a range of dosing strategies.
van de Kerkhof
P C M
PC
Department of Dermatology, University Medical Centre St Radboud, Nijmegen, The Netherlands. p.vandekerkhof@derma.umcn.nl
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001691:Biological Therapy; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D011565:Psoriasis / Q000276:immunology / Q000628:therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000069549:Ustekinumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D053759:Interleukin-23; D018664:Interleukin-12; C544528:briakinumab; D000069549:Ustekinumab