Clinical Review

New Biologics in Psoriasis: An Update on IL-23 and IL-17 Inhibitors

Author and Disclosure Information

As immune-related pathways involved in the pathogenesis of psoriasis are elucidated, new biologic treatments targeting these steps of the psoriatic immune cascade are developed. In this article, we review the literature on IL-23 and IL-17 inhibitors in the pipeline for use in moderate to severe psoriasis. Numerous pipeline biologic therapies, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab, are being investigated in phase 2 and 3 studies to establish the efficacy and safety of these new agents. Of these newest biologics being studied for psoriasis, ixekizumab has been approved and brodalumab is pending approval by the US Food and Drug Administration.

Practice Points

  • The newest biologics for treatment of moderate to severe plaque psoriasis are IL-23 and IL-17 inhibitors with unprecedented efficacy of complete skin clearance compared to older biologics.
  • Risankizumab, guselkumab, and tildrakizumab are new IL-23 inhibitors currently in phase 3 trials with promising early efficacy and safety results.
  • Ixekizumab, which recently was approved, and brodalumab, which is pending US Food and Drug Administration review, are new IL-17 inhibitors that achieved total skin clearance in more than one-quarter of phase 3 participants after 12 weeks of treatment.



The role of current biologic therapies in psoriasis predicates on the pathogenic role of upregulated, immune-related mechanisms that result in the activation of myeloid dendritic cells, which release IL-17, IL-23, and other cytokines to activate T cells, including helper T cell TH17. Along with other immune cells, TH17 produces IL-17. This proinflammatory cascade results in keratinocyte proliferation, angiogenesis, and migration of immune cells toward psoriatic lesions.1 Thus, the newest classes of biologics target IL-12, IL-23, and IL-17 to disrupt this inflammatory cascade.

We provide an updated review of the most recent clinical efficacy and safety data on the newest IL-23 and IL-17 inhibitors in the pipeline or approved for psoriasis, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab (Table). Ustekinumab and adalimumab, which have been previously approved by the US Food and Drug Administration (FDA), will be discussed here only as comparators.

IL-23 Inhibitors


Risankizumab (formerly known as BI 655066)(Boehringer Ingelheim) is a selective human monoclonal antibody targeting the p19 subunit of IL-23 and currently is undergoing phase 3 trials for psoriasis. A proof-of-concept phase 1 study of 39 participants demonstrated efficacy after 12 weeks of treatment at varying subcutaneous and intravenous doses with placebo control.11 At week 12, 87% (27/31)(P<.001) of all risankizumab-treated participants achieved 75% reduction in psoriasis area and severity index (PASI) score compared to 0% of 8 placebo-treated participants. Common adverse effects (AEs) occurred in 65% (20/31) of risankizumab-treated participants, including non–dose-dependent upper respiratory tract infections, nasopharyngitis, and headache. Serious adverse events (SAEs) that occurred were considered unrelated to the study medication.11

A phase 2 trial of 166 participants compared 3 dosing regimens of subcutaneous risankizumab (single 18-mg dose at week 0; single 90-mg dose at weeks 0, 4, and 16; or single 180-mg dose at weeks 0, 4, and 16) and ustekinumab (weight-based single 45- or 90-mg dose at weeks 0, 4, and 16), demonstrating noninferiority at higher doses of risankizumab.2 Preliminary primary end point results at week 12 showed PASI 90 in 32.6% (P=.4667), 73.2% (P=.0013), 81.0% (P<.0001), and 40.0% of the treatment groups, respectively. Participants in the 180-mg risankizumab group achieved PASI 90 eight weeks faster than those on ustekinumab, lasting more than 2 months longer. Adverse effects were similar across all treatment groups and SAEs were unrelated to the study medications.2


Guselkumab (Janssen Biotech, Inc) is a selective human monoclonal antibody against the p19 subunit of IL-23. The 52-week phase 2 X-PLORE trial compared dose-ranging subcutaneous guselkumab (5 mg at weeks 0 and 4, then every 12 weeks; 15 mg every 8 weeks; 50 mg at weeks 0 and 4, then every 12 weeks; 100 mg every 8 weeks; or 200 mg at weeks 0 and 4, then every 12 weeks), adalimumab (80-mg loading dose, followed by 40 mg at week 1, then every other week), and placebo in 293 randomized participants.4 At week 16, 34% (P=.002) of participants in the 5-mg guselkumab group, 61% (P<.001) in the 15-mg group, 79% (P<.001) in the 50-mg group, 86% (P<.001) in the 100-mg group, 83% (P<.001) in the 200-mg group, and 58% (P<.001) in the adalimumab group achieved physician global assessment (PGA) scores of 0 (clear) or 1 (minimal psoriasis) compared to 7% of the placebo group. Achievement of PASI 75 similarly favored the guselkumab (44% [P<.001]; 76% [no P value given]; 81% [P<.001]; 79% [P<.001]; and 81% [P<.001], respectively) and adalimumab treatment arms (70% [P<.001]) compared to 5% in the placebo group. In longer-term comparisons to week 40, participants in the 50-, 100-, and 200-mg guselkumab groups showed significantly greater remission of psoriatic lesions, measured by a PGA score of 0 or 1, than participants in the adalimumab group (71% [P=.05]; 77% [P=.005]; 81% [P=.01]; and 49%, respectively).4

Preliminary results from VOYAGE 1 (N=837), the first of several phase 3 trials, further demonstrate the superiority of guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks over adalimumab (standard dosing) and placebo; at week 16, 73.3% (P<.001 for both comparisons) versus 49.7% and 2.9% of participants, respectively, achieved PASI 90, with sustained superiority of skin clearance in guselkumab-treated participants compared to adalimumab and placebo through week 48.3

Long-term safety data showed no dose dependence or trend from 0 to 16 weeks and 16 to 52 weeks of treatment regarding rates of AEs, SAEs, or serious infections.4 Between weeks 16 and 52, 48.9% of all guselkumab-treated participants exhibited AEs compared to 60.5% of adalimumab-treated participants and 51.3% of placebo participants. Overall infection rates also were lowest in the guselkumab group at 29.8% compared to 36.8% and 35.9%, respectively. Three participants treated with guselkumab had major cardiovascular events, including a fatal myocardial infarction. No cases of tuberculosis or serious opportunistic infections were reported.4


Tildrakizumab (formerly known as MK-3222)(Sun Pharmaceutical Industries Ltd) is a human monoclonal antibody also targeting the p19 subunit of IL-23. In a phase 2 study of 355 participants with chronic plaque psoriasis, participants received 5-, 25-, 100-, or 200-mg subcutaneous tildrakizumab or placebo at weeks 0 and 4 and then every 12 weeks for a total of 52 weeks.6 At week 16, PASI 75 results were 33.3%, 64.4%, 66.3%, 74.4%, and 4.4%, respectively (P<.001 for each comparison). Improvement began within the first month of treatment, with median times to PASI 75 of 57 days at 200-mg dosing and 84 days at 100-mg dosing. Of those participants achieving PASI 75 by drug discontinuation at week 52, 96% of the 100-mg group and 93% of the 200-mg group maintained PASI 75 through week 72, suggesting low relapse rates after treatment cessation.6

In October 2016, the efficacy results of 2 pivotal phase 3 trials (reSURFACE 1 and reSURFACE 2) involving more than 1800 participants combined revealed PASI 90 achievement in an average of 54% of participants on tildrakizumab 100 mg and 59% of participants on tildrakizumab 200 mg at week 28.5 Achievement of PASI 100 occurred in 24% and 30% of participants at week 28, respectively. The second of these trials included an etanercept comparison group and demonstrated head-to-head superiority of 100 and 200 mg subcutaneous tildrakizumab at week 12 by end point measures.5

Treatment-related AEs occurred at rates of 25% in tildrakizumab-treated participants and 22% in placebo-treated participants, most frequently nasopharyngitis and headache.6 At least 1 AE occurred in 64% of tildrakizumab-treated participants without dose dependence compared to 69% of placebo-treated participants. Severe AEs thought to be drug treatment related were bacterial arthritis, lymphedema, melanoma, stroke, and epiglottitis.6


Next Article:

VIDEO: Pediatric psoriasis patients prepare for biologics

Related Articles

  • Fast Facts for Board Review

    Biologics for Psoriasis

    As part of our commitment to resident education, Cutis is excited to offer this monthly section with board-relevant, easy-to-review...