Clinical Review

Emerging Therapies In Psoriasis: A Systematic Review

Author and Disclosure Information

Many new biologics are being studied for use in psoriasis. In this review, we evaluate and summarize findings about emerging biologic therapies for psoriasis. We reviewed published data from phase 2 and 3 clinical trials of 2 IL-17 inhibitors (ixekizumab and brodalumab); 3 IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab); and 1 tumor necrosis factor (TNF) inhibitor (certolizumab pegol). Janus kinase inhibitors were not included in our review, as they currently are not approved by the US Food and Drug Administration (FDA) and there are no plans to further develop this class for treatment of psoriasis. Overall, the clinical improvement provided by and the safety profiles of these agents are promising; they may be equal to or more efficacious than available therapeutic options for treating the symptoms of psoriasis. Long-term studies are still needed, however, to further establish safety and efficacy profiles for these biologic agents.

Practice Points

  • Tumor necrosis factor α, IL-23, and IL-17A are key targets for psoriasis therapy based on an understanding of the key role that these cytokines play in the pathophysiology of disease.
  • The biologic agents secukinumab and ixekizumab are approved for use in the management of psoriasis. Other biologics—brodalumab, bimekizumab, guselkumab, tildrakizumab, risankizumab, and certolizumab pegol—have been (and some continue to be) the focus of phase 2 and phase 3 clinical trials.
  • Findings of several of those trials support the idea that therapies targeting IL-23, specifically its p19 subunit, but that spare IL-12 are effective against psoriasis.
  • Longer-term studies are needed to determine whether the agents reviewed here, including those approved for clinical use, are suitable for prolonged administration.


 

References

Psoriasis is a chronic, autoimmune-mediated disease estimated to affect 2.8% of the US population.1 The pathogenesis of psoriasis is thought to involve a complex process triggered by a combination of genetic and environmental factors that induce tumor necrosis factor (TNF) α secretion by keratinocytes, which in turn activates dendritic cells. Activated dendritic cells produce IL-23, leading to helper T cell (TH17) differentiation.2,3 TH17 cells secrete IL-17A, which has been shown to promote psoriatic skin changes.4 Therefore, TNF-α, IL-23, and IL-17A have been recognized as key targets for psoriasis therapy.

The newest biologic agents targeting IL-17–mediated pathways include ixekizumab, brodalumab, and bimekizumab. Secukinumab, the first US Food and Drug Administration (FDA)–approved IL-17 inhibitor, has been available since 2015 and therefore is not included in this review. IL-23 inhibitors that are FDA approved or being evaluated in clinical trials include guselkumab, tildrakizumab, and risankizumab. In addition, certolizumab pegol, a TNF-α inhibitor, is being studied for use in psoriasis.

METHODS

We reviewed the published results of phase 3 clinical trials for ixekizumab, brodalumab, bimekizumab, guselkumab, tildrakizumab, risankizumab, and certolizumab pegol. We performed an English-language literature search (January 1, 2012 to October 15, 2017) of articles indexed for PubMed/MEDLINE using the following combinations of keywords: IL-23 and psoriasis; IL-17 and psoriasis; tumor necrosis factor and psoriasis; [drug name] and psoriasis. If data from phase 3 clinical trials were not yet available, data from phase 2 clinical trials were incorporated in our analysis. We also reviewed citations within articles to identify relevant sources.

RESULTS

Phase 3 clinical trial design, efficacy, and adverse events (AEs) for ixekizumab and brodalumab are reported in eTable 15-10 and for guselkumab and tildrakizumab in eTable 2.11-14 Phase 2 clinical trial design, efficacy, and AEs are presented for risankizumab in eTable 315-18 and for certolizumab pegol in eTable 4.17,19 No published clinical trial data were found for bimekizumab.

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