Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis

A randomized, double-blind, placebo-controlled, phase II regimen-finding study

Phoebe Rich, B. Sigurgeirsson, D. Thaci, J. P. Ortonne, C. Paul, R. E. Schopf, A. Morita, K. Roseau, E. Harfst, A. Guettner, M. MacHacek, C. Papavassilis

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

Background Interleukin (IL)-17A has major proinflammatory activity in psoriatic lesional skin. Objectives To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-IL-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment-at-start-of- relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). Results At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start-of-relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection-site reactions were reported. Reported cases of neutropenia were mild-to-moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. Conclusions Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis. What's already know about this topic? Conventional systemic therapies for plaque psoriasis have not fully met patient needs. Biologics, although effective and generally well tolerated, have a still-developing long-term safety profile. Monoclonal antibodies against interleukin (IL)-17A have shown early promise. What does this study add? In this regimen-finding study, the investigational anti-IL-17 monoclonal secukinumab (150 mg subcutaneously) showed significant efficacy for induction and maintenance treatment and was well tolerated in moderate-to-severe plaque psoriasis. Secukinumab may offer new therapeutic options in plaque psoriasis.

Original languageEnglish (US)
Pages (from-to)402-411
Number of pages10
JournalBritish Journal of Dermatology
Volume168
Issue number2
DOIs
StatePublished - Feb 1 2013

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Psoriasis
Placebos
Interleukin-17
Recurrence
Safety
Therapeutics
Maintenance
secukinumab
Neutropenia
Biological Products
Immunoglobulin G
Monoclonal Antibodies
Skin
Injections
Antibodies
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Dermatology

Cite this

Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis : A randomized, double-blind, placebo-controlled, phase II regimen-finding study. / Rich, Phoebe; Sigurgeirsson, B.; Thaci, D.; Ortonne, J. P.; Paul, C.; Schopf, R. E.; Morita, A.; Roseau, K.; Harfst, E.; Guettner, A.; MacHacek, M.; Papavassilis, C.

In: British Journal of Dermatology, Vol. 168, No. 2, 01.02.2013, p. 402-411.

Research output: Contribution to journalArticle

Rich, P, Sigurgeirsson, B, Thaci, D, Ortonne, JP, Paul, C, Schopf, RE, Morita, A, Roseau, K, Harfst, E, Guettner, A, MacHacek, M & Papavassilis, C 2013, 'Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: A randomized, double-blind, placebo-controlled, phase II regimen-finding study', British Journal of Dermatology, vol. 168, no. 2, pp. 402-411. https://doi.org/10.1111/bjd.12112
Rich, Phoebe ; Sigurgeirsson, B. ; Thaci, D. ; Ortonne, J. P. ; Paul, C. ; Schopf, R. E. ; Morita, A. ; Roseau, K. ; Harfst, E. ; Guettner, A. ; MacHacek, M. ; Papavassilis, C. / Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis : A randomized, double-blind, placebo-controlled, phase II regimen-finding study. In: British Journal of Dermatology. 2013 ; Vol. 168, No. 2. pp. 402-411.
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title = "Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: A randomized, double-blind, placebo-controlled, phase II regimen-finding study",
abstract = "Background Interleukin (IL)-17A has major proinflammatory activity in psoriatic lesional skin. Objectives To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-IL-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75{\%} improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment-at-start-of- relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). Results At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5{\%} and 42·0{\%} vs. 1·5{\%}; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen [85{\%} (n = 55) and 58{\%} (n = 38), respectively] vs. the start-of-relapse regimen [67{\%} (n = 45), P = 0·020, and 21{\%} (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10{\%} of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection-site reactions were reported. Reported cases of neutropenia were mild-to-moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. Conclusions Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis. What's already know about this topic? Conventional systemic therapies for plaque psoriasis have not fully met patient needs. Biologics, although effective and generally well tolerated, have a still-developing long-term safety profile. Monoclonal antibodies against interleukin (IL)-17A have shown early promise. What does this study add? In this regimen-finding study, the investigational anti-IL-17 monoclonal secukinumab (150 mg subcutaneously) showed significant efficacy for induction and maintenance treatment and was well tolerated in moderate-to-severe plaque psoriasis. Secukinumab may offer new therapeutic options in plaque psoriasis.",
author = "Phoebe Rich and B. Sigurgeirsson and D. Thaci and Ortonne, {J. P.} and C. Paul and Schopf, {R. E.} and A. Morita and K. Roseau and E. Harfst and A. Guettner and M. MacHacek and C. Papavassilis",
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TY - JOUR

T1 - Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis

T2 - A randomized, double-blind, placebo-controlled, phase II regimen-finding study

AU - Rich, Phoebe

AU - Sigurgeirsson, B.

AU - Thaci, D.

AU - Ortonne, J. P.

AU - Paul, C.

AU - Schopf, R. E.

AU - Morita, A.

AU - Roseau, K.

AU - Harfst, E.

AU - Guettner, A.

AU - MacHacek, M.

AU - Papavassilis, C.

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Background Interleukin (IL)-17A has major proinflammatory activity in psoriatic lesional skin. Objectives To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-IL-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment-at-start-of- relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). Results At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start-of-relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection-site reactions were reported. Reported cases of neutropenia were mild-to-moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. Conclusions Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis. What's already know about this topic? Conventional systemic therapies for plaque psoriasis have not fully met patient needs. Biologics, although effective and generally well tolerated, have a still-developing long-term safety profile. Monoclonal antibodies against interleukin (IL)-17A have shown early promise. What does this study add? In this regimen-finding study, the investigational anti-IL-17 monoclonal secukinumab (150 mg subcutaneously) showed significant efficacy for induction and maintenance treatment and was well tolerated in moderate-to-severe plaque psoriasis. Secukinumab may offer new therapeutic options in plaque psoriasis.

AB - Background Interleukin (IL)-17A has major proinflammatory activity in psoriatic lesional skin. Objectives To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-IL-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment-at-start-of- relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). Results At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start-of-relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection-site reactions were reported. Reported cases of neutropenia were mild-to-moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. Conclusions Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis. What's already know about this topic? Conventional systemic therapies for plaque psoriasis have not fully met patient needs. Biologics, although effective and generally well tolerated, have a still-developing long-term safety profile. Monoclonal antibodies against interleukin (IL)-17A have shown early promise. What does this study add? In this regimen-finding study, the investigational anti-IL-17 monoclonal secukinumab (150 mg subcutaneously) showed significant efficacy for induction and maintenance treatment and was well tolerated in moderate-to-severe plaque psoriasis. Secukinumab may offer new therapeutic options in plaque psoriasis.

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