PMID- 36763857
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20230216
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 188
IP  - 2
DP  - 2023 Feb 10
TI  - 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.
PG  - 198-207
LID - 10.1093/bjd/ljac040 [doi]
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.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of British 
      Association of Dermatologists.
FAU - Langley, Richard G
AU  - Langley RG
AD  - Dalhousie University, Halifax, NS, Canada.
FAU - Sofen, Howard
AU  - Sofen H
AUID- ORCID: 0000-0001-7789-6915
AD  - Department of Medicine (Dermatology) UCLA, Los Angeles, CA, USA.
FAU - Dei-Cas, Ignacio
AU  - Dei-Cas I
AD  - Facultad de Medicina de la Universidad de Buenos Aires, Buenos Aires, Argentina.
FAU - Reich, Kristian
AU  - Reich K
AUID- ORCID: 0000-0001-5248-4332
AD  - Translational Research in Inflammatory Skin Diseases, Institute for Health 
      Services Research in Dermatology and Nursing, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Sigurgeirsson, Bardur
AU  - Sigurgeirsson B
AD  - University of Iceland, Reykjavik, Iceland.
FAU - Warren, Richard B
AU  - Warren RB
AUID- ORCID: 0000-0002-2918-6481
AD  - Centre for Dermatology Research, University of Manchester, Manchester, UK.
AD  - Salford Royal NHS Foundation Trust, Manchester, UK.
FAU - Paul, Carle
AU  - Paul C
AUID- ORCID: 0000-0003-0165-5263
AD  - Department of Dermatology, Paul Sabatier University, Toulouse, France.
FAU - Szepietowski, Jacek C
AU  - Szepietowski JC
AUID- ORCID: 0000-0003-0766-6342
AD  - Department of Dermatology, Venereology and Allergology, Wroclaw Medical 
      University, Wroclaw, Poland.
FAU - Tsai, Tsen-Fang
AU  - Tsai TF
AUID- ORCID: 0000-0002-1498-1474
AD  - National Taiwan University Hospital, Taipei, Taiwan.
FAU - Hampele, Isabelle
AU  - Hampele I
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - You, Ruquan
AU  - You R
AD  - China Novartis Institutes for BioMedical Research, Shanghai, China.
FAU - Charef, Pascal
AU  - Charef P
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Papavassilis, Charis
AU  - Papavassilis C
AD  - Novartis Pharma AG, Basel, Switzerland.
LA  - eng
SI  - ClinicalTrials.gov/NCT01544595
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - DLG4EML025 (secukinumab)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Humans
MH  - Quality of Life
MH  - *Nasopharyngitis/chemically induced
MH  - Antibodies, Monoclonal, Humanized/adverse effects
MH  - *Psoriasis/drug therapy
MH  - *Respiratory Tract Infections
MH  - Treatment Outcome
MH  - Severity of Illness Index
MH  - Double-Blind Method
COIS- Conflicts of interest: R.G.L. has served and received compensation in the form of 
      grants and/or honoraria as principal investigator for, is on the scientific 
      advisory board of, or has served as a speaker for AbbVie, Amgen, Boehringer 
      Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer and 
      UCB. H.S. is a clinical investigator for Boehringer Ingelheim, Novartis, Pfizer, 
      Janssen, Lilly, Amgen and Merck; and is a consultant and member of the speakers' 
      bureau for Novartis, Janssen and Lilly. I.D.-C. has received compensation as a 
      speaker, consultant and investigator for Novartis, Eli Lilly and Janssen. K.R. 
      has served as an advisor and/or paid speaker for and/or has participated in 
      clinical trials sponsored by AbbVie, Affibody, Amgen, Biogen, Boehringer 
      Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, 
      Janssen-Cilag, Kyowa Kirin, LEO Pharma, Lilly, Medac, Merck Sharp & Dohme Corp., 
      Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma and 
      Xenoport. B.S. has consulted for Novartis and several other pharmaceutical 
      companies; he has served on an advisory board for Novartis and several other 
      pharmaceutical companies. R.B.W. has received research grants from AbbVie, 
      Almirall, Amgen, Celgene, Janssen, Lilly, LEO Pharma, Novartis, Pfizer and UCB; 
      and consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, 
      Janssen, LEO, Lilly, Novartis, Pfizer, Sanofi, UCB and Xenoport. He is funded by 
      a National Institute for Health Research (NIHR) Clinician Scientist award. He is 
      supported by the NIHR Oxford Biomedical Research Centre. The views expressed are 
      those of the authors and not necessarily those of the National Health Service, 
      the NIHR or the Department of Health. C. Paul has been an investigator and 
      consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, GSK, Janssen, LEO 
      Pharma, Lilly, Novartis and Pfizer. J.C.S. has served on an advisory board for 
      LEO Pharma, Novartis, Sanofi Genzyme, Trevi and Viofor; has been a speaker for 
      AbbVie, LEO Pharma, Novartis, Sanofi Genzyme and Sunfarm; and has served as an 
      investigator for AbbVie, BMS, Galapagos, Galderma, Helm, Incyte, InflaRx, 
      Janssen-Cilag, Novartis, Pfizer, Regeneron, Trevi and UCB. T.-F.T. has served as 
      an investigator and/or speaker and/or advisor for AbbVie, Allergan, BMS, 
      Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, 
      MSD, Novartis, Pfizer, Sanofi Aventis and Tanabe. I.H., R.Y., P.C. and C. 
      Papavassilis are employees of Novartis.
EDAT- 2023/02/11 06:00
MHDA- 2023/02/15 06:00
CRDT- 2023/02/10 15:22
PHST- 2022/01/05 00:00 [received]
PHST- 2022/09/22 00:00 [revised]
PHST- 2022/09/24 00:00 [accepted]
PHST- 2023/02/10 15:22 [entrez]
PHST- 2023/02/11 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
AID - 6765238 [pii]
AID - 10.1093/bjd/ljac040 [doi]
PST - ppublish
SO  - Br J Dermatol. 2023 Feb 10;188(2):198-207. doi: 10.1093/bjd/ljac040.