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Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study.
Br J Dermatol. 2013 Feb; 168(2):412-21.BJ

Abstract

BACKGROUND

Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long-term safety. Interleukin (IL)-17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity.

OBJECTIVES

To assess the efficacy and safety of different doses of secukinumab, a fully human anti-IL-17A IgG1κ monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.

METHODS

Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12-week treatment period, patients entered a follow-up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator's Global Assessment (IGA) and PASI 90 and 50 response rates.

RESULTS

After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow-up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow-up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort.

CONCLUSIONS

Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate-to-severe psoriasis.

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Authors+Show Affiliations

Papp KA
Probity Medical Research, 135 Union Street East, Waterloo, ON N2J 1C4, Canada. kapapp@probitymedical.com
Langley RG
No affiliation info available
Sigurgeirsson B
No affiliation info available
Abe M
No affiliation info available
Baker DR
No affiliation info available
Konno P
No affiliation info available
Haemmerle S
No affiliation info available
Thurston HJ
No affiliation info available
Papavassilis C
No affiliation info available
Richards HB
No affiliation info available

MeSH

Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedBody WeightDermatologic AgentsDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansInjections, IntradermalMaintenance ChemotherapyMaleMiddle AgedPsoriasisTreatment Outcome

Pub Type(s)

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

Language

eng

PubMed ID

23106107

Citation

Papp, K A., et al. "Efficacy and Safety of Secukinumab in the Treatment of Moderate-to-severe Plaque Psoriasis: a Randomized, Double-blind, Placebo-controlled Phase II Dose-ranging Study." The British Journal of Dermatology, vol. 168, no. 2, 2013, pp. 412-21.
Papp KA, Langley RG, Sigurgeirsson B, et al. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. Br J Dermatol. 2013;168(2):412-21.
Papp, K. A., Langley, R. G., Sigurgeirsson, B., Abe, M., Baker, D. R., Konno, P., Haemmerle, S., Thurston, H. J., Papavassilis, C., & Richards, H. B. (2013). Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. The British Journal of Dermatology, 168(2), 412-21. https://doi.org/10.1111/bjd.12110
Papp KA, et al. Efficacy and Safety of Secukinumab in the Treatment of Moderate-to-severe Plaque Psoriasis: a Randomized, Double-blind, Placebo-controlled Phase II Dose-ranging Study. Br J Dermatol. 2013;168(2):412-21. PubMed PMID: 23106107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. AU - Papp,K A, AU - Langley,R G, AU - Sigurgeirsson,B, AU - Abe,M, AU - Baker,D R, AU - Konno,P, AU - Haemmerle,S, AU - Thurston,H J, AU - Papavassilis,C, AU - Richards,H B, Y1 - 2013/01/18/ PY - 2012/10/31/entrez PY - 2012/10/31/pubmed PY - 2013/7/19/medline SP - 412 EP - 21 JF - The British journal of dermatology JO - Br J Dermatol VL - 168 IS - 2 N2 - BACKGROUND: Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long-term safety. Interleukin (IL)-17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity. OBJECTIVES: To assess the efficacy and safety of different doses of secukinumab, a fully human anti-IL-17A IgG1κ monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. METHODS: Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12-week treatment period, patients entered a follow-up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator's Global Assessment (IGA) and PASI 90 and 50 response rates. RESULTS: After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow-up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow-up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort. CONCLUSIONS: Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate-to-severe psoriasis. SN - 1365-2133 UR - https://www.unboundmedicine.com/medline/citation/23106107/Efficacy_and_safety_of_secukinumab_in_the_treatment_of_moderate_to_severe_plaque_psoriasis:_a_randomized_double_blind_placebo_controlled_phase_II_dose_ranging_study_ L2 - https://doi.org/10.1111/bjd.12110 DB - PRIME DP - Unbound Medicine ER -