Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis
Por:
Lebwohl, M, Strober, B, Menter, A, Gordon, K, Weglowska, J, Puig, L, Papp, K, Spelman, L, Toth, D, Kerdel, F, Armstrong, AW, Stingl, G, Kimball, AB, Bachelez, H, Wu, JJ, Crowley, J, Langley, RG, Blicharski, T, Paul, C, Lacour, JP, Tyring, S, Kircik, L, Chimenti, S, Duffin, KC, Bagel, J, Koo, J, Aras, G, Li, J, Song, W, Milmont, CE, Shi, Y, Erondu, N, Klekotka, P, Kotzin, B, Nirula, A
Publicada:
1 oct 2015
Resumen:
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.
Filiaciones:
Lebwohl, M:
Icahn Sch Med Mt Sinai, New York, NY 10029 USA
Strober, B:
Univ Connecticut, Sch Med, Farmington, CT USA
Prob Med Res, Windsor, ON, Canada
Menter, A:
Baylor Univ, Med Ctr, Dallas, TX USA
Gordon, K:
Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA
Weglowska, J:
Niepubl Zaklad Opieki Zdrowotnej MultiMed, Wroclaw, Poland
Puig, L:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Papp, K:
K Papp Med Res, Waterloo, ON, Canada
Spelman, L:
Prob Med Res, Windsor, ON, Canada
Verac Clin Res, Woolloongabba, Qld, Australia
Toth, D:
Prob Med Res, Windsor, ON, Canada
XLR8 Med Res, Windsor, ON, Canada
Kerdel, F:
Florida Acad Dermatol Ctr, Miami, FL USA
Armstrong, AW:
Univ Colorado, Denver, CO 80202 USA
Stingl, G:
Med Univ Wien, Vienna, Austria
Kimball, AB:
Massachusetts Gen Hosp, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Bachelez, H:
Univ Paris Diderot, Sorbonne Paris Cite, AP HP, Hop St Louis, Paris, France
Wu, JJ:
Kaiser Permanente Los Angeles Med Ctr, Los Angeles, CA USA
Crowley, J:
Bakersfield Dermatol & Skin Canc Med Grp, Bakersfield, CA USA
Langley, RG:
Dalhousie Univ, Halifax, NS, Canada
Blicharski, T:
Lubelskie Ctr Diagnost, Swidnik, Poland
Paul, C:
Univ Toulouse 3, F-31062 Toulouse, France
Lacour, JP:
Univ Hosp Nice, Nice, France
Tyring, S:
Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA
Kircik, L:
Icahn Sch Med Mt Sinai, New York, NY 10029 USA
DermResearch, Louisville, KY USA
Chimenti, S:
Univ Roma Tor Vergata, Rome, Italy
Duffin, KC:
Univ Utah, Med Ctr, Salt Lake City, UT USA
Bagel, J:
Psoriasis Treatment Ctr Cent New Jersey, East Windsor, NJ USA
Koo, J:
Univ Calif San Francisco, San Francisco, CA 94143 USA
Aras, G:
Amgen Inc, Thousand Oaks, CA USA
Li, J:
Amgen Inc, Thousand Oaks, CA USA
Song, W:
Amgen Inc, Thousand Oaks, CA USA
Milmont, CE:
Amgen Inc, Thousand Oaks, CA USA
Shi, Y:
Amgen Inc, Thousand Oaks, CA USA
Erondu, N:
Amgen Inc, Thousand Oaks, CA USA
Klekotka, P:
Amgen Inc, Thousand Oaks, CA USA
Kotzin, B:
Amgen Inc, Thousand Oaks, CA USA
Nirula, A:
Amgen Inc, Thousand Oaks, CA USA
Bronze
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