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Meta-Analysis
. 2019 Sep 10;2019:2546161.
doi: 10.1155/2019/2546161. eCollection 2019.

Short-Term Efficacy and Safety of IL-17, IL-12/23, and IL-23 Inhibitors Brodalumab, Secukinumab, Ixekizumab, Ustekinumab, Guselkumab, Tildrakizumab, and Risankizumab for the Treatment of Moderate to Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

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Free PMC article
Meta-Analysis

Short-Term Efficacy and Safety of IL-17, IL-12/23, and IL-23 Inhibitors Brodalumab, Secukinumab, Ixekizumab, Ustekinumab, Guselkumab, Tildrakizumab, and Risankizumab for the Treatment of Moderate to Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Fan Bai et al. J Immunol Res. .
Free PMC article

Abstract

Background: The role of interleukin-12 (IL-12), interleukin-23 (IL-23), and interleukin-17 (IL-17) has been recognized in psoriasis pathogenesis, and new drugs targeting this axis have already been developed which may provide a new therapeutic approach for patients with moderate to severe psoriasis.

Objective: To compare the direct and indirect evidences of the efficacy and safety of brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tildrakizumab, and risankizumab in the short-term treatment of moderate to severe plaque psoriasis using network meta-analysis (NMA).

Methods: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for the available relevant studies. NMA was conducted by Stata 15.0 software using relative risks (RR) with 95% confidence interval to assess the clinical effectiveness and safety. Ranked the efficacy and safety for each drug accordance with the surface under the cumulative ranking curve (SUCRA).

Results: This meta-analysis included 28 studies. All the interventions performed better than placebo in short-term achievement. Based on the result of SUCRA, ixekizumab 80 mg every 2 weeks ranked the highest in short-term achievement of PASI 75 (SUCRA = 93.0%). Brodalumab 210 mg ranked the highest in short-term achievement of PASI 100 (SUCRA = 85.0%). Secukinumab 300 mg ranked the highest in short-term achievement of sPGA 0/1 or IGA 0/1 or PGA 0/1 (SUCRA = 98.1%). In terms of having a risk of adverse events, the rates were higher in brodalumab, secukinumab, ixekizumab, and ustekinumab 45 mg compared with placebo. Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of adverse events during short-term treatment (SUCRA = 4.5%). Guselkumab 50 mg ranked the highest in the risk of serious adverse events during short-term treatment (SUCRA = 25.9%). Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of discontinuations due to adverse events during short-ter treatment (SUCRA = 10.7%).

Conclusions: IL-17, IL-12/23, and IL-23 inhibitors had high efficacy in the achievement of PASI 75, PASI 100, and sPGA 0/1 or IGA 0/1 or PGA 0/1 in moderate to severe plaque psoriasis after 12 or 16 weeks of treatment. IL-17 inhibitors showed superior efficacy. However, its clinical safety was poor. Risankizumab appeared to have relatively high efficacy and low risk. The clinical tolerance of other biological agents needs to be further observed.

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Flowchart for the selection of eligible studies.
Figure 2
Figure 2
Risk of bias summary.
Figure 3
Figure 3
Network plots for all the evaluated outcomes at 12 or 16 weeks. The sizes of the nodes are weighted by the sample of interventions, and the widths of lines are weighed by the number of the studies involved. PASI 75: the percentages of patients with a 75% improvement from baseline in the PASI score; PASI 100: the percentages of patients with a 100% improvement from baseline in the PASI score; sPGA 0/1: static physician's global assessment score of 0 or 1; IGA 0/1: a response of 0 or 1 on the modified investigator's global assessment; PGA 0/1: physician's global assessment score of 0 or 1; AEs: adverse events; sAEs: serious adverse events. Alphabetic reference: A, brodalumab 140 mg; B, brodalumab 210 mg; C, guselkumab 100 mg; D, guselkumab 50 mg; E, ixekizumab 80 mg Q2W; F, ixekizumab 80 mg Q4W; G, placebo; H, risankizumab 150 mg; I, secukinumab 150 mg; J, secukinumab 300 mg; K, tildrakizumab 100 mg; L, tildrakizumab 200 mg; M, ustekinumab 45 mg; and N, ustekinumab 90 mg.
Figure 4
Figure 4
Relative risk with 95% CIs of all interventions from network meta-analysis for PASI 75. Different interventions in the middle block divide the graph into upper and lower triangles; for the lower triangle, the efficacy estimate is the ratio of the column defining treatment to the row defining treatment. In case that the confidence interval does not include 1, if RR > 1, it favors the column defining treatment. In contrast, if RR < 1, it favors the row defining treatment. The upper triangle is symmetrical to the lower triangle. The efficacy estimate is the ratio of the row defining treatment to the column defining treatment. The results are mutually reciprocal. Statistically significant results have been applied with italic formatting.
Figure 5
Figure 5
Relative risk with 95% CIs of all interventions from network meta-analysis for PASI 100. Different interventions in the middle block divide the graph into upper and lower triangles; for the lower triangle, the efficacy estimate is the ratio of the column defining treatment to the row defining treatment. In case that the confidence interval does not include 1, if RR > 1, it favors the column defining treatment. In contrast, if RR < 1, it favors the row defining treatment. The upper triangle is symmetrical to the lower triangle. The efficacy estimate is the ratio of the row defining treatment to the column defining treatment. The results are mutually reciprocal. Statistically significant results have been applied with italic formatting.
Figure 6
Figure 6
Relative risk with 95% CIs of all interventions from network meta-analysis for sPGA 0/1 or IGA 0/1 or PGA 0/1 responses. Different interventions in the middle block divide the graph into upper and lower triangles; for the lower triangle, the efficacy estimate is the ratio of the column defining treatment to the row defining treatment. In case that the confidence interval does not include 1, if RR > 1, it favors the column defining treatment. In contrast, if RR < 1, it favors the row defining treatment. The upper triangle is symmetrical to the lower triangle. The efficacy estimate is the ratio of the row defining treatment to the column defining treatment. The results are mutually reciprocal. Statistically significant results have been applied with italic formatting.
Figure 7
Figure 7
Relative risk with 95% CIs of all interventions from network meta-analysis for adverse events(AEs). Different interventions in the middle block divide the graph into upper and lower triangles; for the lower triangle, the efficacy estimate is the ratio of the column defining treatment to the row defining treatment. In case that the confidence interval does not include 1, if RR > 1, it favors the row defining treatment. In contrast, if RR < 1, it favors the column defining treatment. The upper triangle is symmetrical to the lower triangle. The efficacy estimate is the ratio of the row defining treatment to the column defining treatment. The results are mutually reciprocal. Statistically significant results have been applied with italic formatting.
Figure 8
Figure 8
Relative risk with 95% CIs of all interventions from network meta-analysis for serious adverse events (sAEs). Different interventions in the middle block divide the graph into upper and lower triangles; for the lower triangle, the efficacy estimate is the ratio of the column defining treatment to the row defining treatment. In case that the confidence interval does not include 1, if RR > 1, it favors the row defining treatment. In contrast, if RR < 1, it favors the column defining treatment. The upper triangle is symmetrical to the lower triangle. The efficacy estimate is the ratio of the row defining treatment to the column defining treatment. The results are mutually reciprocal. Statistically significant results have been applied with italic formatting.
Figure 9
Figure 9
Relative risk with 95% CIs of all interventions from network meta-analysis for Discontinuations due to AEs. Different interventions in the middle block divide the graph into upper and lower triangles; for the lower triangle, the efficacy estimate is the ratio of the column defining treatment to the row defining treatment. In case that the confidence interval does not include 1, if RR > 1, it favors the row defining treatment. In contrast, if RR < 1, it favors the column defining treatment. The upper triangle is symmetrical to the lower triangle. The efficacy estimate is the ratio of the row defining treatment to the column defining treatment. The results are mutually reciprocal. Statistically significant results have been applied with italic formatting.
Figure 10
Figure 10
Surface under the cumulative ranking curves (SUCRA) for all interventions of all outcomes in the network meta-analysis. PASI 75: the percentages of patients with a 75% improvement from baseline in the PASI score; PASI 100: the percentages of patients with a 100% improvement from baseline in the PASI score; sPGA 0/1: static physician's global assessment score of 0 or 1; IGA 0/1: a response of 0 or 1 on the modified investigator's global assessment; PGA 0/1: physician's global assessment score of 0 or 1; AEs: adverse events; sAEs: serious adverse events. Alphabetic reference: A, brodalumab 140 mg; B, brodalumab 210 mg, C, guselkumab 100 mg; D, guselkumab 50 mg; E, ixekizumab 80 mg Q2W; F, ixekizumab 80 mg Q4W; G, placebo; H, risankizumab 150 mg; I, secukinumab 150 mg; J, secukinumab 300 mg; K, tildrakizumab 100 mg; L, tildrakizumab 200 mg; M, ustekinumab 45 mg; and N, ustekinumab 90 mg.
Figure 11
Figure 11
Inconsistency in closed loops for all the outcomes. The graph shows the estimates of differences between direct and indirect comparisons as represented by the relative odds ratio (ROR) with 95% CIs. PASI 75: the percentages of patients with a 75% improvement from baseline in the PASI score; PASI 100: the percentages of patients with a 100% improvement from baseline in the PASI score; sPGA 0/1: static physician's global assessment score of 0 or 1; IGA 0/1: a response of 0 or 1 on the modified investigator's global assessment; PGA 0/1: physician's global assessment score of 0 or 1; AEs: adverse events; sAEs: serious adverse events. Alphabetic reference: A, brodalumab 140 mg; B, brodalumab 210 mg; C, guselkumab 100 mg; D, guselkumab 50 mg; E, ixekizumab 80 mg Q2W; F, ixekizumab 80 mg Q4W; G, placebo; H, risankizumab 150 mg; I, secukinumab 150 mg; J, secukinumab 300 mg; K, tildrakizumab 100 mg; L, tildrakizumab 200 mg; M, ustekinumab 45 mg; and N, ustekinumab 90 mg.
Figure 12
Figure 12
Comparison-adjusted funnel plots of all the outcomes in network meta-analysis. PASI 75: the percentages of patients with a 75% improvement from baseline in the PASI score; PASI 100: the percentages of patients with a 100% improvement from baseline in the PASI score; sPGA 0/1: static physician's global assessment score of 0 or 1; IGA 0/1: a response of 0 or 1 on the modified investigator's global assessment; PGA 0/1: physician's global assessment score of 0 or 1; AEs: adverse events; sAEs: serious adverse events. Alphabetic reference: A, brodalumab 140 mg; B, brodalumab 210 mg; C, guselkumab 100 mg; D, guselkumab 50 mg; E, ixekizumab 80 mg Q2W; F, ixekizumab 80 mg Q4W; G, placebo; H, risankizumab 150 mg; I, secukinumab 150 mg; J, secukinumab 300 mg; K, tildrakizumab 100 mg; L, tildrakizumab 200 mg; M, ustekinumab 45 mg; and N, ustekinumab 90 mg.

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References

    1. Stern R. S. Psoriasis. The Lancet. 1997;350(9074):349–353. doi: 10.1016/S0140-6736(97)05257-4. - DOI - PubMed
    1. Michalek I. M., Loring B., John S. M. A systematic review of worldwide epidemiology of psoriasis. Journal of the European Academy of Dermatology and Venereology. 2017;31(2):205–212. doi: 10.1111/jdv.13854. - DOI - PubMed
    1. Parisi R., Symmons D. P., Griffiths C. E., Ashcroft D. M., on behalf of the Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team Global epidemiology of psoriasis: a systematic review of incidence and prevalence. Journal of Investigative Dermatology. 2013;133(2):377–385. doi: 10.1038/jid.2012.339. - DOI - PubMed
    1. Hawkes J. E., Chan T. C., Krueger J. G. Psoriasis pathogenesis and the development of novel targeted immune therapies. The Journal of Allergy and Clinical Immunology. 2017;140(3):645–653. doi: 10.1016/j.jaci.2017.07.004. - DOI - PMC - PubMed
    1. van der Fits L., Mourits S., Voerman J. S. A., et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. Journal of Immunology. 2009;182(9):5836–5845. doi: 10.4049/jimmunol.0802999. - DOI - PubMed

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