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A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis.
Br J Dermatol. 2016 Aug; 175(2):273-86.BJ

Abstract

BACKGROUND

The interleukin-17 cytokine family plays a central role in psoriasis pathogenesis.

OBJECTIVES

To evaluate the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor antibody, in treating patients with moderate-to-severe plaque psoriasis.

METHODS

In this phase III, double-blind, placebo-controlled study (NCT01708590; AMAGINE-1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12-week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA ≥ 3 were re-treated with the induction dose. After ≥ 12 weeks of retreatment, patients with sPGA 2 for ≥ 4 weeks or sPGA ≥ 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA ≥ 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with ≥ 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12.

RESULTS

There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable.

CONCLUSIONS

Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate-to-severe plaque psoriasis.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada.

Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany.

Paul Sabatier University, Toulouse, France.

Oregon Medical Research Center, Portland, OR, U.S.A.

Wroclaw Medical University, Wroclaw, Poland.

The University of Montreal and Innovaderm Research, Montreal, QC, Canada.

XLR8 Medical Research and Probity Medical Research, Windsor, ON, Canada.

Dalhousie University, Halifax, NS, Canada.

Modern Research Associates, Modern Dermatology, A Baylor Health Texas Affiliate, and Probity Medical Research, Dallas, TX, U.S.A.

Tufts Medical Center, Boston, MA, U.S.A.

University of Lübeck, Lübeck, Germany.

The Rockefeller University, New York, NY, U.S.A.

Amgen Inc., Thousand Oaks, CA, U.S.A.

Amgen Inc., Thousand Oaks, CA, U.S.A.

Amgen Inc., Thousand Oaks, CA, U.S.A.

Amgen Inc., Thousand Oaks, CA, U.S.A.

Amgen Inc., Thousand Oaks, CA, U.S.A.

Amgen Inc., Thousand Oaks, CA, U.S.A.

MeSH

Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedAnxiety DisordersBiomarkersDepressive DisorderDermatologic AgentsDouble-Blind MethodDrug Administration ScheduleDrug SubstitutionFemaleHumansMaleMiddle AgedPatient SafetyPsoriasisRetreatmentTreatment Outcome

Pub Type(s)

Clinical Trial, Phase III

Journal Article

Multicenter Study

Randomized Controlled Trial

Language

eng

PubMed ID

26914406

Citation

Papp, K A., et al. "A Prospective Phase III, Randomized, Double-blind, Placebo-controlled Study of Brodalumab in Patients With Moderate-to-severe Plaque Psoriasis." The British Journal of Dermatology, vol. 175, no. 2, 2016, pp. 273-86.

Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175(2):273-86.

Papp, K. A., Reich, K., Paul, C., Blauvelt, A., Baran, W., Bolduc, C., Toth, D., Langley, R. G., Cather, J., Gottlieb, A. B., Thaçi, D., Krueger, J. G., Russell, C. B., Milmont, C. E., Li, J., Klekotka, P. A., Kricorian, G., & Nirula, A. (2016). A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. The British Journal of Dermatology, 175(2), 273-86. https://doi.org/10.1111/bjd.14493

Papp KA, et al. A Prospective Phase III, Randomized, Double-blind, Placebo-controlled Study of Brodalumab in Patients With Moderate-to-severe Plaque Psoriasis. Br J Dermatol. 2016;175(2):273-86. PubMed PMID: 26914406.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. AU - Papp,K A, AU - Reich,K, AU - Paul,C, AU - Blauvelt,A, AU - Baran,W, AU - Bolduc,C, AU - Toth,D, AU - Langley,R G, AU - Cather,J, AU - Gottlieb,A B, AU - Thaçi,D, AU - Krueger,J G, AU - Russell,C B, AU - Milmont,C E, AU - Li,J, AU - Klekotka,P A, AU - Kricorian,G, AU - Nirula,A, Y1 - 2016/06/23/ PY - 2016/02/15/accepted PY - 2016/2/26/entrez PY - 2016/2/26/pubmed PY - 2017/7/25/medline SP - 273 EP - 86 JF - The British journal of dermatology JO - Br J Dermatol VL - 175 IS - 2 N2 - BACKGROUND: The interleukin-17 cytokine family plays a central role in psoriasis pathogenesis. OBJECTIVES: To evaluate the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor antibody, in treating patients with moderate-to-severe plaque psoriasis. METHODS: In this phase III, double-blind, placebo-controlled study (NCT01708590; AMAGINE-1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12-week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA ≥ 3 were re-treated with the induction dose. After ≥ 12 weeks of retreatment, patients with sPGA 2 for ≥ 4 weeks or sPGA ≥ 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA ≥ 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with ≥ 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12. RESULTS: There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable. CONCLUSIONS: Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate-to-severe plaque psoriasis. SN - 1365-2133 UR - https://www.unboundmedicine.com/medline/citation/26914406/A_prospective_phase_III_randomized_double_blind_placebo_controlled_study_of_brodalumab_in_patients_with_moderate_to_severe_plaque_psoriasis_ DB - PRIME DP - Unbound Medicine ER -