Author

Study type

Cohort

Treatment

Regimen

Clinical evaluation

Experimental evaluation

Conclusion

Phototherapy

Coimbra et al. [96]

Cross-sectional and longitudinal study

34 PsV patients; 20 healthy controls

NB-UVB and PUVA phototherapy

17 patients received NB-UVB  and remaining 17 patients received PUVA; administration at weeks 0, 3, 6, and 12

24 patients achieved PASI 75 and 7 patients achieved PASI 50; Mean PASI reduction was significantly larger for the NB-UVB cohort (P ≤ 0.01)

Decrease in IL-23, TNF-α, IL-22, IL-17, VEGF, and IL-8 over treatment duration

Phototherapy is clinically effective at reducing Th17-related cytokine levels

Johnson-Huang [95]

Prospective trial

14 psoriatics

NB-UVB phototherapy

Applied in increments of 5-10% dose,  3-4 times per week, for up to 6 weeks

93% patients achieved PASI 50 and 28% patients achieved PASI 75

Decrease in number of inflammatory dendritic cells and their products, IL-20, IL-12/23p40, and IL-23p19; reduced IL-17 and IL-22 mRNA expression

NB-UVB radiation therapy can target the IL-17 pathway to resolve psoriatic inflammation

Conventional

Lowes et al. [7]

Prospective trial

11 PsV patients

Cyclosporine

Patients received cyclosporine at 4 mg/kg daily

N/A

Decrease in IL-17, IFN-γ, and IL-22 mRNA levels

Cyclosporine is clinically effective at reducing Th17-related cytokine levels

Biologics

Kagami et al. [35]

Open-label study

5 psoriatics

Infliximuab

IV infusion 5mg/kg at wks 0, 2, 6, 14, and 22 weeks

Mean decrease in PASI from 7.7 (week 0) to 3.7 (week 14)

Decrease in circulating levels of Th17 and Th1 cells

Infliximab is effective at reducing circulating Th17 cells

Caproni et al. [98]

Randomized, controlled trial

60 PtPs patients

Etanercept, Acitretin

30 patients received etanercept 50 mg 2x/wk and 30 patients received acitretin 0.4 mg/kg daily, both over 12 weeks

57% of etanercept cohort and 27% of acitretin cohort achieved PASI 75; Mean PASI reduction was significantly larger for the etanercept cohort (p= 0.005)

Etanercept achieved a significant reduction in IL-17 and IL-22 levels, while acitretin did not

Etanercept is able to reduceTh17 expression and is  more clinically effective than acitretin

Zaba et al. [99]

Prospective trial

15 PsV patients

Etanercept

Patients received etanercept 50mg 2x/weekly for 12 weeks

11 responded while 4 did not respond**

Only responders inactivated myeloid dendritic cell genes and the Th17 immune response

Clinical response to TNF inhibitors such as etanercept is mediated via down regulation of IL-17 pathway genes

Suarez-Farinas [100]

Prospective trial

20 psoriatics

Etanercept

Subcutaneous treatment (50mg) 2x/weekly for 12 weeks

11 responded while 9 did not**

IL-22 and IL-17 gene expression did not reduce by > 75% after etanercept treatment although resolved skin pathological T cells were > 95% reduced based on CD3+ cell counts

While etanercept can fully resolve epidermal reaction in psoriasis, inflammation, defined by the expression of Th17 cytokines and chemokines, continues to persist

Zaba et al. [101]

Prospective trial

20 psoriatics

Etanercept

Subcutaneous treatment (50mg) 2x/weekly for 12 weeks

16 patients responded and 4 did not**

Decrease in number of inflammatory dendritic cell products (IL-12/23p40) and Th17 cell products (IL-17, IL-22, CCL20, and β-defensin 4)

Clinical response to TNF inhibitors such as etanercept is mediated via down regulation of IL-17 pathway genes

Hueber et al. [103]

Double-blind, placebo-controlled parallel-group study

36 PtPs patients

Secukinumab (AIN457)

Random, single infusion of either AIN457 (3-10 mg/kg) or saline (placebo) and monitored over 12 weeks

Mean PASI reduced by 58% and 4% in the AIN457 and placebo-treated groups, respectively;

AIN457 treatment resulted in significant decrease of dermal IL-17A+ CD3+ T cells; mRNA expression of IL-17 and IL-22 were also markedly reduced

The targeted inhibition of IL-17A with AIN457 is a valid therapeutic approach in the treatment of psoriasis