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).
The phase 3 STATURE trial assessed the safety and effectiveness of SC and IV AIN457 in moderate to severe psoriasis in partial AIN457 nonresponders.29 Nonresponders were participants who demonstrated a PASI score of 50% or more but less than 75%. Participants in this study design who received SC AIN457 demonstrated a PASI 75 of 66.7%, with a 2011 investigator global assessment score of 0 (clear) or 1 (almost clear) in 66.7%. In those receiving IV AIN457, the PASI 75 was 90.5%, with a 2011 investigator global assessment score of 0 or 1 in 33.3%.29
In a 52-week phase 3 efficacy trial (known as FIXTURE), 1306 participants received 1 dose of AIN457 300 mg or 150 mg weekly for 5 weeks, then every 4 weeks; 12 weeks of etanercept 50 mg twice weekly, then once weekly; or placebo. The PASI 75 was 77.1% for AIN457 300 mg, 67.0% for AIN457 150 mg, 44.0% for etanercept, and 4.9% for placebo (P<.001).30 In a 52-week efficacy and safety trial (known as ERASURE), 738 participants received 1 dose of AIN457 300 mg or 150 mg weekly for 5 weeks, then every 4 weeks, versus placebo. The PASI 75 was 65.3% for AIN457 300 mg, 51.2% for AIN457 150 mg, and 2.4% for placebo (P<.001). There was a comparable incidence of infection among participants with AIN457 and etanercept, which was greater than placebo.30
Brodalumab (AMG 827)
Brodalumab (formerly known as AMG 827)(Amgen Inc) is a human monoclonal antibody that targets the IL-17A receptor. In a phase 1 randomized trial, 25 participants received either IV brodalumab 700 mg, SC brodalumab 350 mg or 140 mg, or placebo.31 Results demonstrated improvement in PASI score that correlated with increased dosage of brodalumab as well as decreased psoriasis gene expression and decreased thickness of the epidermis in participants receiving the 700-mg IV or 350-mg SC doses. In a phase 2 trial, 198 participants received either brodalumab 280 mg at week 0, then every 4 weeks for 8 weeks, or brodalumab 210 mg, 140 mg, 70 mg, or placebo at week 0, then every 2 weeks for 10 weeks. At week 12, PASI 75 was observed in 82% and 77% of the 210-mg and 140-mg groups, respectively, with no benefit noted in the placebo group (P<.001).31 In a phase 3 trial, 661 participants received brodalumab 210 mg or 140 mg or placebo. At week 12, PASI 75 was observed in 83% of the 210-mg group versus 60% of the 140-mg group; PASI 100 was observed in 42% of the 210-mg group versus 23% of the 140-mg group.32
Ixekizumab (LY2439821)
Ixekizumab (formerly known as LY2439821)(Eli Lilly and Company) is a human monoclonal antibody that targets IL-17A. In a phase 2 double-blind, placebo-controlled trial, 142 participants with chronic moderate to severe plaque psoriasis were randomized to receive 10-mg, 25-mg, 75-mg, or 150-mg SC injections of ixekizumab or placebo at 0, 2, 4, 8, 12, and 16 weeks. At week 12, the percentage of participants with a 75% reduction in PASI score was significantly greater with ixekizumab (150 mg [82.1%], 75 mg [82.8%], and 25 mg [76.7%]), except the 10-mg group, than with placebo (7.7%)(P<.001 for each comparison).33
Inhibition of T-Cell Activation in Antigen-Presenting Cells
Abatacept
Abatacept (Bristol-Myers Squibb) is a fusion protein designed to inhibit T-cell activation by binding receptors for CD80 and CD86 in antigen-presenting cells.34 A phase 1 study of 43 participants demonstrated improved PGA scores of 50% in 46% of psoriasis participants who were treated with abatacept, indicating a dose-responsive association with abatacept in psoriasis patients refractory to other therapies.35 In a 6-month, phase 2, multicenter, randomized, double-blind, placebo-controlled trial, 170 participants with PsA were randomized to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg followed by 10 mg/kg).36 At day 169, ACR20 was observed in 19%, 33%, 48%, and 42% of the placebo and abatacept 3 mg/kg, 10 mg/kg, and 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10-mg/kg (P=.006) and 30/10-mg/kg (P=.022) groups but not for the 3-mg/kg group (P=.121). The authors concluded that abatacept 10 mg/kg could be an appropriate dosing regimen for PsA, as is presently used in the FDA-approved management of rheumatoid arthritis.36 At the time of publication, a phase 3 trial evaluating the efficacy and safety of abatacept SC injection in adults with active PsA was ongoing but was not actively recruiting participants (NCT01860976).
Activation of Regulatory T Cells
Tregalizumab (BT061)
Tregalizumab (formerly known as BT061)(Biotest) is a human monoclonal antibody that activates regulatory T cells. A phase 2, randomized, placebo-controlled, double-blind, multicenter, multiple-dose, cohort study with escalating doses evaluating the safety and efficacy of BT061 in patients with moderate to severe chronic plaque psoriasis was completed, but the results were not available at the time of publication (NCT01072383).
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