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Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis.
N Engl J Med. 2015 Oct; 373(14):1318-28.NEJM

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.).

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Lebwohl M
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.).
Strober B
No affiliation info available
Menter A
No affiliation info available
Gordon K
No affiliation info available
Weglowska J
No affiliation info available
Puig L
No affiliation info available
Papp K
No affiliation info available
Spelman L
No affiliation info available
Toth D
No affiliation info available
Kerdel F
No affiliation info available
Armstrong AW
No affiliation info available
Stingl G
No affiliation info available
Kimball AB
No affiliation info available
Bachelez H
No affiliation info available
Wu JJ
No affiliation info available
Crowley J
No affiliation info available
Langley RG
No affiliation info available
Blicharski T
No affiliation info available
Paul C
No affiliation info available
Lacour JP
No affiliation info available
Tyring S
No affiliation info available
Kircik L
No affiliation info available
Chimenti S
No affiliation info available
Callis Duffin K
No affiliation info available
Bagel J
No affiliation info available
Koo J
No affiliation info available
Aras G
No affiliation info available
Li J
No affiliation info available
Song W
No affiliation info available
Milmont CE
No affiliation info available
Shi Y
No affiliation info available
Erondu N
No affiliation info available
Klekotka P
No affiliation info available
Kotzin B
No affiliation info available
Nirula A
No affiliation info available

MeSH

AdolescentAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCandidiasisDouble-Blind MethodDrug Administration ScheduleFemaleHumansMaleMiddle AgedNeutropeniaPsoriasisReceptors, Interleukin-17Severity of Illness IndexTreatment OutcomeUstekinumabYoung Adult

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26422722

Clinical Trial Links

Clinical trial which this article describes [1]
Clinical trial which this article describes [2]

Citation

Lebwohl, Mark, et al. "Phase 3 Studies Comparing Brodalumab With Ustekinumab in Psoriasis." The New England Journal of Medicine, vol. 373, no. 14, 2015, pp. 1318-28.
Lebwohl M, Strober B, Menter A, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med. 2015;373(14):1318-28.
Lebwohl, M., Strober, B., Menter, A., Gordon, K., Weglowska, J., Puig, L., Papp, K., Spelman, L., Toth, D., Kerdel, F., Armstrong, A. W., Stingl, G., Kimball, A. B., Bachelez, H., Wu, J. J., Crowley, J., Langley, R. G., Blicharski, T., Paul, C., ... Nirula, A. (2015). Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. The New England Journal of Medicine, 373(14), 1318-28. https://doi.org/10.1056/NEJMoa1503824
Lebwohl M, et al. Phase 3 Studies Comparing Brodalumab With Ustekinumab in Psoriasis. N Engl J Med. 2015;373(14):1318-28. PubMed PMID: 26422722.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. AU - Lebwohl,Mark, AU - Strober,Bruce, AU - Menter,Alan, AU - Gordon,Kenneth, AU - Weglowska,Jolanta, AU - Puig,Lluis, AU - Papp,Kim, AU - Spelman,Lynda, AU - Toth,Darryl, AU - Kerdel,Francisco, AU - Armstrong,April W, AU - Stingl,Georg, AU - Kimball,Alexa B, AU - Bachelez,Herve, AU - Wu,Jashin J, AU - Crowley,Jeffrey, AU - Langley,Richard G, AU - Blicharski,Tomasz, AU - Paul,Carle, AU - Lacour,Jean-Philippe, AU - Tyring,Stephen, AU - Kircik,Leon, AU - Chimenti,Sergio, AU - Callis Duffin,Kristina, AU - Bagel,Jerry, AU - Koo,John, AU - Aras,Gary, AU - Li,Joanne, AU - Song,Wenjie, AU - Milmont,Cassandra E, AU - Shi,Yifei, AU - Erondu,Ngozi, AU - Klekotka,Paul, AU - Kotzin,Brian, AU - Nirula,Ajay, PY - 2015/10/1/entrez PY - 2015/10/1/pubmed PY - 2015/10/9/medline SP - 1318 EP - 28 JF - The New England journal of medicine JO - N Engl J Med VL - 373 IS - 14 N2 - 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.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/26422722/Phase_3_Studies_Comparing_Brodalumab_with_Ustekinumab_in_Psoriasis_ DB - PRIME DP - Unbound Medicine ER -