Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis

CLUSTER Consortium; Lucy R Wedderburn; Athimalaipet V Ramanan; Adam P Croft; Kimme L Hyrich; Andrew D Dick

doi:10.1136/ard-2022-222553

Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis

CLUSTER Consortium, Lucy R Wedderburn^*, Athimalaipet V Ramanan, Adam P Croft, Kimme L Hyrich, Andrew D Dick

^*Corresponding author for this work

Inflammation and Ageing

Research output: Contribution to journal › Review article › peer-review

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Abstract

In childhood arthritis, collectively known as Juvenile idiopathic arthritis (JIA), the rapid rise of available licensed biological and targeted small molecule treatments in recent years has led to improved outcomes. However, real-world data from multiple countries and registries show that despite a large number of available drugs, many children and young people continue to suffer flares and experience significant periods of time with active disease for many years. More than 50% of young people with JIA require ongoing immune suppression well into adult life, and they may have to try multiple different treatments in that time. There are currently no validated tools with which to select specific treatments, nor biomarkers of response to assist in such choices, therefore, current management uses essentially a trial-and-error approach. A further consequence of recent progress is a reducing pool of available children or young people who are eligible for new trials. In this review we consider how progress towards a molecular based approach to defining treatment targets and informing trial design in JIA, combined with novel approaches to clinical trials, could provide strategies to maximise discovery and progress, in order to move towards precision medicine for children with arthritis.

Original language	English
Journal	Annals of the Rheumatic Diseases
Early online date	5 Dec 2022
DOIs	https://doi.org/10.1136/ard-2022-222553
Publication status	E-pub ahead of print - 5 Dec 2022

Bibliographical note

Funding:
CLUSTER is funded by the UKRI MRC (MR/R013926/1), Versus Arthritis (22084) and GOS Charity (VS0518). LRW is supported by the NIHR Great Ormond Street Biomedical Research Centre. CLUSTER is also supported by GSK, Pfizer, AbbVie, UCB and SOBI. LRW declares consultancy fees paid by Pfizer to UCL for an unrelated project. KLH has received honoraria from AbbVie and grants from Pfizer and BMS. KLH is supported by the NIHR Manchester Biomedical Research Centre. AD declares consultancy paid by 4-DMT, UCL, Activebio, Hubble Tx, Novartis, UCB, Alimera, Revolobio Janssen and cofounder of Cirrus Therapeutic and is supported by the NIHR Moorfields Biomedical Research Centre. AVR declares Speaker fees/Honoraria/ Consultancy from AbbVie, Eli Lilly, Pfizer, Roche, Novartis, SOBI, GSK, Astra Zeneca and UCB. APC declares consultancy fees paid by Eli Lilly for an unrelated project. APC is supported by the NIHR Birmingham Biomedical Research Centre.

Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

Keywords

Child
Adult
Humans
Adolescent
Arthritis, Juvenile/drug therapy
Precision Medicine
Registries

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10.1136/ard-2022-222553Licence: Creative Commons: Attribution (CC BY)

WedderburnL2022TowardsFinal published version, 917 KBLicence: Creative Commons: Attribution (CC BY)

Cite this

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title = "Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis",

abstract = "In childhood arthritis, collectively known as Juvenile idiopathic arthritis (JIA), the rapid rise of available licensed biological and targeted small molecule treatments in recent years has led to improved outcomes. However, real-world data from multiple countries and registries show that despite a large number of available drugs, many children and young people continue to suffer flares and experience significant periods of time with active disease for many years. More than 50% of young people with JIA require ongoing immune suppression well into adult life, and they may have to try multiple different treatments in that time. There are currently no validated tools with which to select specific treatments, nor biomarkers of response to assist in such choices, therefore, current management uses essentially a trial-and-error approach. A further consequence of recent progress is a reducing pool of available children or young people who are eligible for new trials. In this review we consider how progress towards a molecular based approach to defining treatment targets and informing trial design in JIA, combined with novel approaches to clinical trials, could provide strategies to maximise discovery and progress, in order to move towards precision medicine for children with arthritis.",

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author = "{CLUSTER Consortium} and Wedderburn, {Lucy R} and Ramanan, {Athimalaipet V} and Croft, {Adam P} and Hyrich, {Kimme L} and Dick, {Andrew D}",

note = "Funding: CLUSTER is funded by the UKRI MRC (MR/R013926/1), Versus Arthritis (22084) and GOS Charity (VS0518). LRW is supported by the NIHR Great Ormond Street Biomedical Research Centre. CLUSTER is also supported by GSK, Pfizer, AbbVie, UCB and SOBI. LRW declares consultancy fees paid by Pfizer to UCL for an unrelated project. KLH has received honoraria from AbbVie and grants from Pfizer and BMS. KLH is supported by the NIHR Manchester Biomedical Research Centre. AD declares consultancy paid by 4-DMT, UCL, Activebio, Hubble Tx, Novartis, UCB, Alimera, Revolobio Janssen and cofounder of Cirrus Therapeutic and is supported by the NIHR Moorfields Biomedical Research Centre. AVR declares Speaker fees/Honoraria/ Consultancy from AbbVie, Eli Lilly, Pfizer, Roche, Novartis, SOBI, GSK, Astra Zeneca and UCB. APC declares consultancy fees paid by Eli Lilly for an unrelated project. APC is supported by the NIHR Birmingham Biomedical Research Centre. Copyright: {\textcopyright} Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.",

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language = "English",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

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AU - CLUSTER Consortium

AU - Wedderburn, Lucy R

AU - Ramanan, Athimalaipet V

AU - Croft, Adam P

AU - Hyrich, Kimme L

AU - Dick, Andrew D

N1 - Funding: CLUSTER is funded by the UKRI MRC (MR/R013926/1), Versus Arthritis (22084) and GOS Charity (VS0518). LRW is supported by the NIHR Great Ormond Street Biomedical Research Centre. CLUSTER is also supported by GSK, Pfizer, AbbVie, UCB and SOBI. LRW declares consultancy fees paid by Pfizer to UCL for an unrelated project. KLH has received honoraria from AbbVie and grants from Pfizer and BMS. KLH is supported by the NIHR Manchester Biomedical Research Centre. AD declares consultancy paid by 4-DMT, UCL, Activebio, Hubble Tx, Novartis, UCB, Alimera, Revolobio Janssen and cofounder of Cirrus Therapeutic and is supported by the NIHR Moorfields Biomedical Research Centre. AVR declares Speaker fees/Honoraria/ Consultancy from AbbVie, Eli Lilly, Pfizer, Roche, Novartis, SOBI, GSK, Astra Zeneca and UCB. APC declares consultancy fees paid by Eli Lilly for an unrelated project. APC is supported by the NIHR Birmingham Biomedical Research Centre. Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

PY - 2022/12/5

Y1 - 2022/12/5

N2 - In childhood arthritis, collectively known as Juvenile idiopathic arthritis (JIA), the rapid rise of available licensed biological and targeted small molecule treatments in recent years has led to improved outcomes. However, real-world data from multiple countries and registries show that despite a large number of available drugs, many children and young people continue to suffer flares and experience significant periods of time with active disease for many years. More than 50% of young people with JIA require ongoing immune suppression well into adult life, and they may have to try multiple different treatments in that time. There are currently no validated tools with which to select specific treatments, nor biomarkers of response to assist in such choices, therefore, current management uses essentially a trial-and-error approach. A further consequence of recent progress is a reducing pool of available children or young people who are eligible for new trials. In this review we consider how progress towards a molecular based approach to defining treatment targets and informing trial design in JIA, combined with novel approaches to clinical trials, could provide strategies to maximise discovery and progress, in order to move towards precision medicine for children with arthritis.

AB - In childhood arthritis, collectively known as Juvenile idiopathic arthritis (JIA), the rapid rise of available licensed biological and targeted small molecule treatments in recent years has led to improved outcomes. However, real-world data from multiple countries and registries show that despite a large number of available drugs, many children and young people continue to suffer flares and experience significant periods of time with active disease for many years. More than 50% of young people with JIA require ongoing immune suppression well into adult life, and they may have to try multiple different treatments in that time. There are currently no validated tools with which to select specific treatments, nor biomarkers of response to assist in such choices, therefore, current management uses essentially a trial-and-error approach. A further consequence of recent progress is a reducing pool of available children or young people who are eligible for new trials. In this review we consider how progress towards a molecular based approach to defining treatment targets and informing trial design in JIA, combined with novel approaches to clinical trials, could provide strategies to maximise discovery and progress, in order to move towards precision medicine for children with arthritis.

KW - Child

KW - Adult

KW - Humans

KW - Adolescent

KW - Arthritis, Juvenile/drug therapy

KW - Precision Medicine

KW - Registries

U2 - 10.1136/ard-2022-222553

DO - 10.1136/ard-2022-222553

M3 - Review article

C2 - 36600186

SN - 0003-4967

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

ER -

Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis

Abstract

Bibliographical note

Keywords

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Cite this