Journal of Clinical and Aesthetic Dermatology

Updates on Psoriasis & Cutaneou Oncology

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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S21 P r o c e e D i n G s JCAD jOUrnAl Of ClInICAl And AEsthEtIC dErMAtOlOgy september 2017 • volume 10 • number 9 • supplement involved. 100 iBrodalumab significantly reduced psoriasis in 12 weeks, with 72 percent of patients achieving Pasi 90 scores. adverse events occurred, the most common of which were nasopharyngitis, upper respiratory tract infection, and injection-site erythema; two cases of neutropenia were reported in the group that received brodalumab 210mg. 100 Brodalumab was able to reverse gene expression across thousands of genes in psoriatic skin. 101 ixekizumab was evaluated by leonardi et al in a 12-week Phase-2, placebo-controlled study of 142 patients with moderate-to-severe psoriasis. signifcant improvement with ixekizumab versus placebo emerged in some patients in the frst week. 102 secukinumab, ixekizumab, and brodalumab were all able to target il-17 and produce dramatic results in psoriatic skin, but the question remained as to the potential impact of maximal ligand blocking to suppress the entire downstream pathway. upstream from th-17 (and il-17) is il-23. it was hypothesized that il-23 might control the entire tH17 pathway, 103 and the potential blockade of il-23 and th17 was proposed as a topic for further study. the humanized anti-il-23 antibody guselkumab was evaluated in the treatment of moderate- to-severe psoriasis with promising results. 104 in a 28-week study, 70.0 percent of guselkumab patients versus 2.4 percent of placebo patients achieved Pasi 90 scores at 16 weeks. 105 risankizumab, a relatively new il-23 antibody, 106 was shown to markedly reduce psoriasis in a Phase 2 clinical trial (n=166), providing signifcantly superior results to the active comparator in the trial, ustekinumab. 107 By the 12th week, the percentage of patients who achieved at least a 90-percent reduction in their baseline Pasi score was 77 vs. 40 percent for risankizumab and ustekinumab, respectively (p<0.001). serious adverse events were reported in all but one of the study arms: risankizumab 18mg (12%), risankizumab 90mg (15%), risankizumab 180mg (0), and ustekinumab 45mg or 90mg based on body weight (8%). 107 other il-23 antagonists currently being studied include B1644066 and tildrakiuzumab. it appears that the il-23/th17 axis is crucial to sustaining psoriasis over time, and biologics that target this axis are showing dramatic results, which allow dermatologists to claim that psoriasis is the most edectively treated of all human autoimmune diseases. 108 this has led to the elucidation of the feed-forward il-17 pathogenesis model where autoantigens directly or indirectly mediated by il-17 trigger il-23/il-17 pathways, which begin a cascade including myeloid dendritic t-cell interactions; activated t-cell subpopulations; and the production of il-17a, il-22, and ifnγ, which in turn allow keratinocytes to "feed-forward" the ingammatory mediators and then amplify cellular immunity and sustain chronic t-cell activation. 108 thus, psoriasis vulgaris may be regarded as the chronic and maladaptive activation of the body's natural immune response aimed at eliminating the Candida albicans and possibly other extracellular pathogens. However, psoriasis is driven by an autoantigen rather than an exogenous one. it has long been noted that patients with psoriasis are generally highly resistant to Staphylococcus aureus infection in contrast to patients with atopic dermatitis. tAblE 4. summary of the il-17 family 96,97 I l fAMIly r ECEPtOr M AIn fUnCtIOns d rUgs r EsUlts i l-17a i l-17ra and il-17rc a utoimmune pathology, neutrophil recruitment, immunity to extracellular pathogens secukinumab i xekizumab brodalumab these agents are highly e dective in clearing psoriasis but less edective in reducing other i mmunopathologies il-17B il-17rB suspected pro-ingammatory activity n/a n/a il-17c il-17re suspected pro-ingammatory activity n/a n/a il-17D not known suspected pro-ingammatory activity n/a n/a il-17e il-17ra and il-17rB induces th2 cell responses and suppresses th17 cell responses n/a n/a il-17f il-17ra and il-17rc neutrophil recruitment and immunity to extracellular pathogens brodalumab edective in clearing psoriasis but reports emerged about increasing suicidal ideation; approved in 2017 il-17a to il-17f hereodimer il-17ra and il-17rc suspected activity related to autoimmune pathology, neutrophil recruitment, immunity to extracellular pathogens n/a n/a il: interleukin; th: t helper cells; n/a: not applicable

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