Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials
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Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials. / Langley, Richard G; Sofen, Howard; Dei-Cas, Ignacio; Reich, Kristian; Sigurgeirsson, Bardur; Warren, Richard B; Paul, Carle; Szepietowski, Jacek C; Tsai, Tsen-Fang; Hampele, Isabelle; You, Ruquan; Charef, Pascal; Papavassilis, Charis.
in: BRIT J DERMATOL, Jahrgang 188, Nr. 2, 10.02.2023, S. 198-207.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials
AU - Langley, Richard G
AU - Sofen, Howard
AU - Dei-Cas, Ignacio
AU - Reich, Kristian
AU - Sigurgeirsson, Bardur
AU - Warren, Richard B
AU - Paul, Carle
AU - Szepietowski, Jacek C
AU - Tsai, Tsen-Fang
AU - Hampele, Isabelle
AU - You, Ruquan
AU - Charef, Pascal
AU - Papavassilis, Charis
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.
PY - 2023/2/10
Y1 - 2023/2/10
N2 - BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis.OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis.METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595.RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively.CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.
AB - BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis.OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis.METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595.RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively.CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.
KW - Humans
KW - Quality of Life
KW - Nasopharyngitis/chemically induced
KW - Antibodies, Monoclonal, Humanized/adverse effects
KW - Psoriasis/drug therapy
KW - Respiratory Tract Infections
KW - Treatment Outcome
KW - Severity of Illness Index
KW - Double-Blind Method
U2 - 10.1093/bjd/ljac040
DO - 10.1093/bjd/ljac040
M3 - SCORING: Journal article
C2 - 36763857
VL - 188
SP - 198
EP - 207
JO - BRIT J DERMATOL
JF - BRIT J DERMATOL
SN - 0007-0963
IS - 2
ER -