Clinical Review
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Novel Psoriasis Therapies and Patient Outcomes, Part 1: Topical Medications
In recent years, advances in our understanding of inflammatory mediators and the underlying pathogenesis of psoriasis and psoriatic arthritis have...
Meghan A. Feely, MD; Barry L. Smith, MD; Jeffrey M. Weinberg, MD
From the Department of Dermatology, Mount Sinai St. Luke’s-Roosevelt and Beth Israel Medical Centers of the Icahn School of Medicine at Mount Sinai, New York, New York.
Drs. Feely and Smith report no conflict of interest. Dr. Weinberg is an investigator and speaker for AbbVie, Inc; Amgen Inc; and Novartis Pharmaceutical Corporation.
This article is the second of a 3-part series. The third part will appear in July 2015.
Correspondence: Meghan A. Feely, MD, Department of Dermatology, Icahn School of Medicine at Mount Sinai, Mount Sinai St. Luke’s-Roosevelt, 1090 Amsterdam Ave, Ste 11B, New York, NY 10025 (mfeely@chpnet.org).
Several clinical trials are underway and are currently recruiting participants (Table 2).
Guselkumab (CNTO 1959)
Guselkumab (formerly known as CNTO 1959)(Janssen Research & Development, LLC) is a human monoclonal antibody targeting the p19 subunit of IL-23. In a double-blind, randomized study of 24 participants receiving 1 dose of CNTO 1959 at 10 mg, 30 mg, 100 mg, or 300 mg versus placebo, a PASI 75 of 50% for the 10-mg subset, 60% for the 30- and 100-mg group, and 100% for the 300-mg group was achieved as opposed to 0% in the placebo group at 12 weeks.22 The rate of AEs was 65% in the CNTO 1959 treatment arm versus 50% in the placebo group at 24 weeks. Furthermore, decreased serum IL-17A titers and gene expression for psoriasis was demonstrated as well as decreased thickness of the epidermis and less dendritic and T-cell expression for the CNTO 1959 study population histologically.22 Results of a phase 2 trial in 293 participants who received CNTO 1959, adalimumab, or placebo indicated PASI 75 at 16 weeks for 81% of the CNTO 1959 50-mg group versus 71% of the adalimumab group, with serious AEs in 3% of participants treated with CNTO 1959 versus 5% treated with adalimumab.23
Tildrakizumab (MK-3222/SCH 900222)
Tildrakizumab (formerly known as MK-3222/SCH 900222)(Merck & Co Inc) is a monoclonal antibody that also targets the p19 subunit of IL-23. Results of a phase 2b trial were promising. This study reported on 355 participants who received placebo versus MK-3222 5 mg, 25 mg, 100 mg, or 200 mg, with PASI 75 scores of 4.4%, 33%, 64%, 66%, and 74%, respectively, noted at 16 weeks.24 A 64-week phase 3 study currently is underway to assess the long-term benefit and safety of MK-3222, but it is not recruiting participants (NCT01722331).
Inhibition of the IL-17 Pathway
The T helper 17 cells (TH17) produce IL-17, a cytokine mediating inflammation that is implicated in psoriasis. Two products target IL-17A, while another targets the IL-17 receptor.25
Secukinumab (AIN457)
Secukinumab (formerly known as AIN457)(Novartis Pharmaceutical Corporation) was FDA approved for treatment of moderate to severe psoriasis in adult patients who are candidates for systemic therapy or phototherapy in January 2015.26 Secukinumab is a human monoclonal antibody that inhibits IL-17A. There are many clinical trials underway including a phase 2 extension study (NCT01132612). Many phase 3 studies also are underway evaluating the effectiveness and safety of AIN457 in patients with psoriasis resistant to TNF inhibitors (NCT01961609); its usability and tolerability (NCT01555125), including 2-year extension studies (NCT01640951; NCT01544595); its effectiveness as opposed to ustekinumab (NCT02074982); effectiveness using an autoinjector (NCT01636687); and the PASI 90 in HLA-Cw6–positive and HLA-Cw6–negative patients with moderate to severe psoriasis (known as SUPREME)(NCT02394561).
Other phase 3 trials are being undertaken in patients with moderate to severe palmoplantar psoriasis (NCT01806597; NCT02008890); moderate to severe nail psoriasis (known as TRANSFIGURE)(NCT01807520); moderate to severe scalp psoriasis (NCT02267135); and PsA (NCT01989468; NCT02294227; NCT01892436), including a 5-year study for PsA (known as FUTURE 2)(NCT01752634).
Other studies that are completed with pending results include a phase 1 trial to evaluate its mechanism of action in vivo by studying the spread of AIN457 in tissue as assessed by open flow microperfusion (NCT01539213), a phase 2 trial of the clinical effectiveness of AIN457 at 12 months and biomarker changes (NCT01537432), as well as phase 3 trials of the clinical efficacy of various dosing regimens (known as SCULPTURE)(NCT01406938); safety and effectiveness at 1 year (known as ERASURE)(NCT01365455); and the effectiveness, tolerability, and safety of AIN457 over 2 years in PsA (known as FUTURE 1)(NCT01392326).
In a 56-week phase 2 clinical trial of 100 participants, the PASI scores at 12 weeks and percentage of participants without relapse up to 56 weeks were evaluated.27 There were 4 arms in the study: (1) AIN457 3 mg/kg (day 1) then placebo (days 15 and 29); (2) AIN457 10 mg/kg (day 1) then placebo (days 15 and 29); (3) AIN457 10 mg/kg (days 1, 15, and 29); and (4) placebo (days 1, 15, and 29), with AIN457 and the placebo administered IV. The mean (standard deviation) change from baseline for PASI scores for these respective groups was -12.46 (7.668), -13.35 (6.195), -18.02 (6.792), and -4.18 (4.698), respectively. At week 56, the percentage of participants without a relapse at any point during the study was 12.5%, 22.2%, and 27.8%, respectively.27
In a phase 2 study of 404 participants, PASI 75 scores were assessed at 12 weeks with the SC administration of AIN457 in participants with moderate to severe psoriasis at 3 dosing regimens: (1) a single dose of 150 mg (week 1), (2) monthly doses of 150 mg (weeks 1, 5, and 9), (3) early loading doses of 150 mg (weeks 1, 2, 3, 5, and 9), as compared to placebo. At 12 weeks, PASI 75 scores were 7%, 58%, 72%, and 1%, respectively.28
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