PMID- 37722926
OWN - NLM
STAT- MEDLINE
DCOM- 20231120
LR  - 20231120
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 189
IP  - 6
DP  - 2023 Nov 16
TI  - Efficacy and safety of ciclosporin versus methotrexate in the treatment of severe 
      atopic dermatitis in children and young people (TREAT): a multicentre parallel 
      group assessor-blinded clinical trial.
PG  - 674-684
LID - 10.1093/bjd/ljad281 [doi]
AB  - BACKGROUND: Conventional systemic drugs are used to treat children and young 
      people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust 
      randomized controlled trial (RCT) evidence exists regarding their efficacy and 
      safety in this population. While novel therapies have expanded therapeutic 
      options, their high cost means traditional agents remain important, especially in 
      lower-resource settings. OBJECTIVES: To compare the safety and efficacy of 
      ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment 
      of severe Atopic Eczema Trial (TREAT) trial. METHODS: We conducted a parallel 
      group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 
      2-16 years and unresponsive to potent topical treatment were randomized to either 
      oral CyA (4 mg kg-1 daily) or MTX (0.4 mg kg-1 weekly) for 36 weeks and 
      followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 
      weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to 
      first significant flare (relapse) after treatment cessation. Secondary outcomes 
      included change in quality of life (QoL) from baseline to 60 weeks; number of 
      participant-reported flares following treatment cessation; proportion of 
      participants achieving >/= 50% improvement in Eczema Area and Severity Index (EASI 
      50) and >/= 75% improvement in EASI (EASI 75); and stratification of outcomes by 
      filaggrin status. RESULTS: In total, 103 participants were randomized (May 
      2016-February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in 
      disease severity by 12 weeks [mean difference in o-SCORAD -5.69, 97.5% confidence 
      interval (CI) -10.81 to -0.57 (P = 0.01)]. More participants achieved >/= 50% 
      improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm 
      [odds ratio (OR) 2.60, 95% CI 1.23-5.49; P = 0.01]. By 60 weeks MTX was superior 
      (OR 0.33, 95% CI 0.13-0.85; P = 0.02), a trend also seen for >/= 75% improvement in 
      o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares 
      post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42-6.01; P = 0.02). 
      QoL improved with both treatments and was sustained after treatment cessation. 
      Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) 
      was comparable between both treatments. Five (10%) participants on CyA and seven 
      (14%) on MTX experienced a serious AE. CONCLUSIONS: Both CyA and MTX proved 
      effective in CYP with severe AD over 36 weeks. Participants who received CyA 
      showed a more rapid response to treatment, while MTX induced more sustained 
      disease control after discontinuation.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of British 
      Association of Dermatologists.
FAU - Flohr, Carsten
AU  - Flohr C
AUID- ORCID: 0000-0003-4884-6286
AD  - Department of Paediatric Dermatology, St John's Institute of Dermatology, King's 
      College London and Guy's and St Thomas' NHS Foundation Trust, London, UK.
FAU - Rosala-Hallas, Anna
AU  - Rosala-Hallas A
AD  - Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
FAU - Jones, Ashley P
AU  - Jones AP
AD  - Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
FAU - Beattie, Paula
AU  - Beattie P
AD  - Royal Hospital for Children NHS Trust, Glasgow, UK.
FAU - Baron, Susannah
AU  - Baron S
AD  - Department of Paediatric Dermatology, St John's Institute of Dermatology, King's 
      College London and Guy's and St Thomas' NHS Foundation Trust, London, UK.
FAU - Browne, Fiona
AU  - Browne F
AD  - Paediatric Dermatology, Children's Health Ireland at Crumlin, Dublin, Ireland.
FAU - Brown, Sara J
AU  - Brown SJ
AD  - Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, 
      UK.
FAU - Gach, Joanna E
AU  - Gach JE
AD  - University Hospitals Coventry and Warwickshire, Coventry, UK.
FAU - Greenblatt, Danielle
AU  - Greenblatt D
AD  - Department of Paediatric Dermatology, St John's Institute of Dermatology, King's 
      College London and Guy's and St Thomas' NHS Foundation Trust, London, UK.
FAU - Hearn, Ross
AU  - Hearn R
AD  - Ninewells Hospital and Medical School, Dundee, UK.
FAU - Hilger, Eva
AU  - Hilger E
AD  - Department of Paediatric Dermatology, St John's Institute of Dermatology, King's 
      College London and Guy's and St Thomas' NHS Foundation Trust, London, UK.
FAU - Esdaile, Ben
AU  - Esdaile B
AD  - Whittington Hospital, Whittington Health NHS Trust, London, UK.
FAU - Cork, Michael J
AU  - Cork MJ
AD  - Sheffield Children's NHS Foundation Trust and Sheffield Dermatology Research, 
      Department of Infection, Immunity and Cardiovascular Disease, University of 
      Sheffield, Sheffield, UK.
FAU - Howard, Emma
AU  - Howard E
AD  - Department of Paediatric Dermatology, St John's Institute of Dermatology, King's 
      College London and Guy's and St Thomas' NHS Foundation Trust, London, UK.
FAU - Lovgren, Marie-Louise
AU  - Lovgren ML
AD  - Birmingham Children's Hospital, Birmingham Women's and Children's NHS Foundation 
      Trust, Birmingham, UK.
FAU - August, Suzannah
AU  - August S
AD  - University Hospitals Dorset NHS Foundation Trust, Poole, UK.
FAU - Ashoor, Farhiya
AU  - Ashoor F
AD  - Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
FAU - Williamson, Paula R
AU  - Williamson PR
AD  - Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
FAU - McPherson, Tess
AU  - McPherson T
AD  - Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
FAU - O'Kane, Donal
AU  - O'Kane D
AD  - Department of Dermatology, Belfast Health and Social Care Trust, Belfast, UK.
FAU - Ravenscroft, Jane
AU  - Ravenscroft J
AUID- ORCID: 0000-0002-1609-7084
AD  - Nottingham University Hospitals NHS Trust, Nottingham, UK.
FAU - Shaw, Lindsay
AU  - Shaw L
AD  - Bristol Royal Hospital for Children, Bristol, UK.
FAU - Sinha, Manish D
AU  - Sinha MD
AD  - Kings College London, Department of Paediatric Nephrology, Evelina London 
      Children's Hospital, Guy's & St Thomas's Foundation Hospitals NHS Trust, London.
FAU - Spowart, Catherine
AU  - Spowart C
AD  - Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
FAU - Taams, Leonie S
AU  - Taams LS
AUID- ORCID: 0000-0002-9337-7194
AD  - Centre for Inflammation Biology and Cancer Immunology, King's College London, UK.
FAU - Thomas, Bjorn R
AU  - Thomas BR
AUID- ORCID: 0000-0002-1815-3502
AD  - Royal Free Hospital and Blizard Institute, Queen Mary University London, UK.
FAU - Wan, Mandy
AU  - Wan M
AD  - Evelina London Children's Hospital, Guys' and St Thomas' NHS Foundation Trust, 
      London, UK.
AD  - Institute of Pharmaceutical Science, King's College London, London, UK.
FAU - Sach, Tracey H
AU  - Sach TH
AUID- ORCID: 0000-0002-8098-9220
AD  - Health Economics Group, Norwich Medical School, University of East Anglia, 
      Norwich, UK.
FAU - Irvine, Alan D
AU  - Irvine AD
AD  - Paediatric Dermatology, Children's Health Ireland at Crumlin, Dublin, Ireland.
AD  - Clinical Medicine, Trinity College Dublin, Ireland.
AD  - National Children's Research Centre, Crumlin, Dublin, Ireland.
CN  - TREAT Trial Investigators
LA  - eng
GR  - 15/EE/0328/UK Medical Research Council/National Institute for Health Research 
      Efficacy and Mechanism Evaluation Board/
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - YL5FZ2Y5U1 (Methotrexate)
RN  - 0 (Filaggrin Proteins)
SB  - IM
CIN - Br J Dermatol. 2023 Nov 16;189(6):e105. PMID: 37972137
EIN - Br J Dermatol. 2023 Nov 16;:. PMID: 37972208
MH  - Child
MH  - Humans
MH  - Adolescent
MH  - *Cyclosporine/adverse effects
MH  - Methotrexate/adverse effects
MH  - *Dermatitis, Atopic/drug therapy
MH  - Filaggrin Proteins
MH  - Odds Ratio
MH  - Treatment Outcome
MH  - Severity of Illness Index
MH  - Double-Blind Method
COIS- Conflicts of interest C.F. is Chief Investigator of the UK National Institute for 
      Health Research-funded TREAT (ISRCTN15837754) and SOFTER (ClinicalTrials.gov: 
      NCT03270566) trials, as well as the UK-Irish Atopic eczema Systemic Therapy 
      Register (A-STAR; ISRCTN11210918) and a Principal Investigator in the European 
      Union (EU) Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu). He 
      also leads the EU Trans-Foods consortium. His department has received 
      investigator-led funding from Sanofi-Genzyme and Pfizer for microbiome work. 
      D.O'K. has received funding for advisory board participation with Sanofi-Genzyme. 
      M.W. is a steering committee member of A-STAR (ISRCTN11210918). T.M. has received 
      funding for advisory boards and teaching from Sanofi-Genzyme, AbbVie and Pfizer. 
      M.J.C. has received investigator-led funding from Hyphens Pharma, Johnson & 
      Johnson, Sanofi, L'Oreal, LEO Pharma, ACO Nordic, Pfizer, Regeneron and 
      Sanofi-Genzyme, as well as funding for advisory board participation with Menlo. 
      He has also received consultant fees from Boots, Eli Lilly and Procter & Gamble. 
      S.J.B. is a medical advisor to the Ichthyosis Support Group and Eczema Outreach 
      Support and has received funding from the Wellcome Trust. A.D.I. has received 
      consulting fees from Area, Almirall, AbbVie, Pfizer, Eli Lilly and 
      Sanofi-Regeneron, and is the Director of the International Eczema Council. 
      A.R.-H., A.P.J., B.R.T., C.S., M.-L.L., E. Hilger, M.D.S., F.A., F.B., D.G., 
      P.B., B.E., J.E.G., S.A., S.B., P.R.W., L.S.T., R.H., T.H.S., E. Howard, J.R. and 
      L.S. declare no conflicts of interest.
FIR - Layton, Alison
IR  - Layton A
FIR - Burton, Tim
IR  - Burton T
FIR - Grainge, Michael
IR  - Grainge M
FIR - Arden-Jones, Michael
IR  - Arden-Jones M
FIR - King, Saskia
IR  - King S
FIR - Perkin, Michael
IR  - Perkin M
FIR - Taieb, Alain
IR  - Taieb A
FIR - Ormerod, Anthony
IR  - Ormerod A
FIR - Chalmers, Robert
IR  - Chalmers R
FIR - Liu, Xinxue
IR  - Liu X
FIR - Ahmed, Amina
IR  - Ahmed A
FIR - Ashoor, Farhiya
IR  - Ashoor F
FIR - Flohr, Carsten
IR  - Flohr C
FIR - Rosala-Hallas, Anna
IR  - Rosala-Hallas A
FIR - Holton, Amy
IR  - Holton A
FIR - Mason, Hannah
IR  - Mason H
FIR - Irvine, Alan
IR  - Irvine A
FIR - Jones, Ashley
IR  - Jones A
FIR - Sach, Tracey
IR  - Sach T
FIR - Spowart, Catherine
IR  - Spowart C
FIR - Wan, Mandy
IR  - Wan M
FIR - Walker, Charlotte
IR  - Walker C
FIR - August, Suzannah
IR  - August S
FIR - Beattie, Paula
IR  - Beattie P
FIR - Brown, Sara
IR  - Brown S
FIR - Cork, Mike
IR  - Cork M
FIR - Esdaile, Ben
IR  - Esdaile B
FIR - Flohr, Carsten
IR  - Flohr C
FIR - Gach, Joanna
IR  - Gach J
FIR - Howard, Emma
IR  - Howard E
FIR - Irvine, Alan
IR  - Irvine A
FIR - McPherson, Tess
IR  - McPherson T
FIR - O'Kane, Donal
IR  - O'Kane D
FIR - Ravenscroft, Jane
IR  - Ravenscroft J
FIR - Shaw, Lindsay
IR  - Shaw L
FIR - Allen, Caroline
IR  - Allen C
FIR - Baron, Susannah
IR  - Baron S
FIR - Greenblatt, Danielle
IR  - Greenblatt D
FIR - Hearn, Robert
IR  - Hearn R
FIR - Hoey, Susannah
IR  - Hoey S
FIR - Jarret, Rachael
IR  - Jarret R
FIR - Jury, Catherine
IR  - Jury C
FIR - Mitchell, Charlie
IR  - Mitchell C
FIR - Murphy, Ruth
IR  - Murphy R
FIR - Ogg, Graham
IR  - Ogg G
FIR - Plant, Alice
IR  - Plant A
FIR - Newell, Louise
IR  - Newell L
FIR - Srinivasan, Jothsana
IR  - Srinivasan J
FIR - Wedgeworth, Emma
IR  - Wedgeworth E
FIR - Browne, Fiona
IR  - Browne F
EDAT- 2023/09/19 00:43
MHDA- 2023/11/20 06:54
CRDT- 2023/09/18 21:42
PHST- 2023/03/21 00:00 [received]
PHST- 2023/08/01 00:00 [revised]
PHST- 2023/11/20 06:54 [medline]
PHST- 2023/09/19 00:43 [pubmed]
PHST- 2023/09/18 21:42 [entrez]
AID - 7276541 [pii]
AID - 10.1093/bjd/ljad281 [doi]
PST - ppublish
SO  - Br J Dermatol. 2023 Nov 16;189(6):674-684. doi: 10.1093/bjd/ljad281.