title: Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis.
abstract: BACKGROUND
  Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.
  
  
  METHODS
  In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100).
  
  
  RESULTS
  At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab.
  
  
  CONCLUSIONS
  Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).
authors.affiliation: From the Icahn School of Medicine at Mount Sinai, New York (M.L., L.K.); University of Connecticut School of Medicine, Farmington (B.S.); Probity Medical Research (B.S., L.S., D.T.) and XLR8 Medical Research (D.T.), Windsor, ON, K Papp Medical Research (K.P.), Waterloo, ON, and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Baylor University Medical Center, Dallas (A.M.); Northwestern University, Feinberg School of Medicine, Chicago (K.G.); Niepubliczny Zakład Opieki Zdrowotnej multiMedica, Wrocław (J.W.), and Lubelskie Centrum Diagnostyczne, Świdnik (T.B.) - both in Poland; Hospital de la Santa Creu i Sant Pau, Barcelona (L.P.); Veracity Clinical Research, Woolloongabba, QLD, Australia (L.S.); Florida Academic Dermatology Center, Miami (F.K.); University of Colorado, Denver (A.W.A.); Medizinische Universität Wien, Vienna, Austria (G.S.); Massachusetts General Hospital and Harvard Medical School, Boston (A.B.K.); Sorbonne Paris Cité Université Paris Diderot, Assistance Publique-Hôpitaux de Paris Hôpital Saint Louis, Paris (H.B.), Paul Sabatier University, Toulouse (C.P.), and University Hospital of Nice, Nice (J.-P.L.) - all in France; Kaiser Permanente Los Angeles Medical Center, Los Angeles (J.J.W.), Bakersfield Dermatology and Skin Cancer Medical Group, Bakersfield (J.C.), University of California, San Francisco, San Francisco (J.K.), and Amgen, Thousand Oaks (G.A., J.L., W.S., C.E.M., Y.S., N.E., P.K., B.K., A.N.) - all in California.; University of Texas Health Science Center, Houston (S.T.); DermResearch, Louisville, KY (L.K.); University of Rome Tor Vergata, Rome (S.C.); University of Utah Medical Center, Salt Lake City (K.C.D.); and the Psoriasis Treatment Center of Central New Jersey, East Windsor (J.B.).
authors.forename: Mark
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authors.lastname: Lebwohl
authors.forename: Bruce
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authors.lastname: Strober
authors.forename: Alan
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authors.lastname: Menter
authors.forename: Kenneth
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authors.lastname: Gordon
authors.forename: Jolanta
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authors.forename: Lluis
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authors.lastname: Puig
authors.forename: Kim
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authors.lastname: Papp
authors.forename: Lynda
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authors.lastname: Spelman
authors.forename: Darryl
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authors.lastname: Toth
authors.forename: Francisco
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authors.lastname: Kerdel
authors.forename: April W
authors.initials: AW
authors.lastname: Armstrong
authors.forename: Georg
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authors.lastname: Stingl
authors.forename: Alexa B
authors.initials: AB
authors.lastname: Kimball
authors.forename: Herve
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authors.lastname: Bachelez
authors.forename: Jashin J
authors.initials: JJ
authors.lastname: Wu
authors.forename: Jeffrey
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authors.lastname: Crowley
authors.forename: Richard G
authors.initials: RG
authors.lastname: Langley
authors.forename: Tomasz
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authors.lastname: Blicharski
authors.forename: Carle
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authors.lastname: Paul
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lacour
authors.forename: Stephen
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authors.lastname: Tyring
authors.forename: Leon
authors.initials: L
authors.lastname: Kircik
authors.forename: Sergio
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authors.lastname: Chimenti
authors.forename: Kristina
authors.initials: K
authors.lastname: Callis Duffin
authors.forename: Jerry
authors.initials: J
authors.lastname: Bagel
authors.forename: John
authors.initials: J
authors.lastname: Koo
authors.forename: Gary
authors.initials: G
authors.lastname: Aras
authors.forename: Joanne
authors.initials: J
authors.lastname: Li
authors.forename: Wenjie
authors.initials: W
authors.lastname: Song
authors.forename: Cassandra E
authors.initials: CE
authors.lastname: Milmont
authors.forename: Yifei
authors.initials: Y
authors.lastname: Shi
authors.forename: Ngozi
authors.initials: N
authors.lastname: Erondu
authors.forename: Paul
authors.initials: P
authors.lastname: Klekotka
authors.forename: Brian
authors.initials: B
authors.lastname: Kotzin
authors.forename: Ajay
authors.initials: A
authors.lastname: Nirula
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D002177:Candidiasis / Q000209:etiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy*; D053722:Receptors, Interleukin-17 / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000069549:Ustekinumab; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053722:Receptors, Interleukin-17; C571216:brodalumab; D000069549:Ustekinumab