Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): A multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol

Mariam Al-Laith; Marianna Jasenecova; Sonya Abraham; Aisla Bosworth; Ian N. Bruce; Christopher D. Buckley; Coziana Ciurtin; Maria Antonietta D'Agostino; Paul Emery; Hill Gaston; John D. Isaacs; Andrew Filer; Benjamin A. Fisher; Thomas W.J. Huizinga; Pauline Ho; Clare Jacklin; Heidi Lempp; Iain B. McInnes; Arthur G. Pratt; Andrew Östor; Karim Raza; Peter C. Taylor; Dirkjan Van Schaardenburg; Dharshene Shivapatham; Alison J. Wright; Joana C. Vasconcelos; Joanna Kelly; Caroline Murphy; A. Toby Prevost; Andrew P. Cope

doi:10.1186/s13063-019-3403-7

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): A multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol

Mariam Al-Laith^*, Marianna Jasenecova, Sonya Abraham, Aisla Bosworth, Ian N. Bruce, Christopher D. Buckley, Coziana Ciurtin, Maria Antonietta D'Agostino, Paul Emery, Hill Gaston, John D. Isaacs, Andrew Filer, Benjamin A. Fisher, Thomas W.J. Huizinga, Pauline Ho, Clare Jacklin, Heidi Lempp, Iain B. McInnes, Arthur G. Pratt, Andrew ÖstorKarim Raza, Peter C. Taylor, Dirkjan Van Schaardenburg, Dharshene Shivapatham, Alison J. Wright, Joana C. Vasconcelos, Joanna Kelly, Caroline Murphy, A. Toby Prevost, Andrew P. Cope

^*Corresponding author for this work

Inflammation and Ageing

Research output: Contribution to journal › Article › peer-review

Abstract

Trial design: We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods: The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study. Conclusions: There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the "at risk" state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration: Current Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014.

Original language	English
Article number	429
Journal	Trials
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s13063-019-3403-7
Publication status	Published - 15 Jul 2019

Bibliographical note

Funding Information:
The APIPPRA study is funded through an IMI101–328 Immunoscience Investigator research grant awarded to King’s College London by Bristol-Myers Squibb.

Funding Information:
The authors acknowledge the support of the National Institute for Health Research (NIHR) National Office for Clinical Research Infrastructure Translational Research Collaboration for Joint and Related Inflammatory Diseases and the support of their affiliated NIHR Biomedical Research Centres.

Publisher Copyright:
© 2019 The Author(s).

Keywords

Abatacept
Antibodies to citrullinated protein antigens
At risk
Autoantibodies
Double-blind
Intervention
Placebo-controlled
Pre-clinical phase
Randomised
Rheumatoid arthritis

ASJC Scopus subject areas

Medicine (miscellaneous)
Pharmacology (medical)

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10.1186/s13063-019-3403-7

Cite this

Al-Laith, M., Jasenecova, M., Abraham, S., Bosworth, A., Bruce, I. N., Buckley, C. D., Ciurtin, C., D'Agostino, M. A., Emery, P., Gaston, H., Isaacs, J. D., Filer, A., Fisher, B. A., Huizinga, T. W. J., Ho, P., Jacklin, C., Lempp, H., McInnes, I. B., Pratt, A. G., ... Cope, A. P. (2019). Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): A multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol. Trials, 20(1), Article 429. https://doi.org/10.1186/s13063-019-3403-7

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title = "Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): A multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol",

abstract = "Trial design: We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods: The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study. Conclusions: There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the {"}at risk{"} state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration: Current Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014.",

keywords = "Abatacept, Antibodies to citrullinated protein antigens, At risk, Autoantibodies, Double-blind, Intervention, Placebo-controlled, Pre-clinical phase, Randomised, Rheumatoid arthritis",

author = "Mariam Al-Laith and Marianna Jasenecova and Sonya Abraham and Aisla Bosworth and Bruce, {Ian N.} and Buckley, {Christopher D.} and Coziana Ciurtin and D'Agostino, {Maria Antonietta} and Paul Emery and Hill Gaston and Isaacs, {John D.} and Andrew Filer and Fisher, {Benjamin A.} and Huizinga, {Thomas W.J.} and Pauline Ho and Clare Jacklin and Heidi Lempp and McInnes, {Iain B.} and Pratt, {Arthur G.} and Andrew {\"O}stor and Karim Raza and Taylor, {Peter C.} and {Van Schaardenburg}, Dirkjan and Dharshene Shivapatham and Wright, {Alison J.} and Vasconcelos, {Joana C.} and Joanna Kelly and Caroline Murphy and Prevost, {A. Toby} and Cope, {Andrew P.}",

note = "Funding Information: The APIPPRA study is funded through an IMI101–328 Immunoscience Investigator research grant awarded to King{\textquoteright}s College London by Bristol-Myers Squibb. Funding Information: The authors acknowledge the support of the National Institute for Health Research (NIHR) National Office for Clinical Research Infrastructure Translational Research Collaboration for Joint and Related Inflammatory Diseases and the support of their affiliated NIHR Biomedical Research Centres. Publisher Copyright: {\textcopyright} 2019 The Author(s).",

year = "2019",

month = jul,

day = "15",

doi = "10.1186/s13063-019-3403-7",

language = "English",

volume = "20",

journal = "Trials",

issn = "1745-6215",

publisher = "Springer",

number = "1",

}

Al-Laith, M, Jasenecova, M, Abraham, S, Bosworth, A, Bruce, IN, Buckley, CD, Ciurtin, C, D'Agostino, MA, Emery, P, Gaston, H, Isaacs, JD, Filer, A , Fisher, BA, Huizinga, TWJ, Ho, P, Jacklin, C, Lempp, H, McInnes, IB, Pratt, AG, Östor, A, Raza, K, Taylor, PC, Van Schaardenburg, D, Shivapatham, D, Wright, AJ, Vasconcelos, JC, Kelly, J, Murphy, C, Prevost, AT & Cope, AP 2019, 'Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): A multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol', Trials, vol. 20, no. 1, 429. https://doi.org/10.1186/s13063-019-3403-7

TY - JOUR

T1 - Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study)

T2 - A multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol

AU - Al-Laith, Mariam

AU - Jasenecova, Marianna

AU - Abraham, Sonya

AU - Bosworth, Aisla

AU - Bruce, Ian N.

AU - Buckley, Christopher D.

AU - Ciurtin, Coziana

AU - D'Agostino, Maria Antonietta

AU - Emery, Paul

AU - Gaston, Hill

AU - Isaacs, John D.

AU - Filer, Andrew

AU - Fisher, Benjamin A.

AU - Huizinga, Thomas W.J.

AU - Ho, Pauline

AU - Jacklin, Clare

AU - Lempp, Heidi

AU - McInnes, Iain B.

AU - Pratt, Arthur G.

AU - Östor, Andrew

AU - Raza, Karim

AU - Taylor, Peter C.

AU - Van Schaardenburg, Dirkjan

AU - Shivapatham, Dharshene

AU - Wright, Alison J.

AU - Vasconcelos, Joana C.

AU - Kelly, Joanna

AU - Murphy, Caroline

AU - Prevost, A. Toby

AU - Cope, Andrew P.

N1 - Funding Information: The APIPPRA study is funded through an IMI101–328 Immunoscience Investigator research grant awarded to King’s College London by Bristol-Myers Squibb. Funding Information: The authors acknowledge the support of the National Institute for Health Research (NIHR) National Office for Clinical Research Infrastructure Translational Research Collaboration for Joint and Related Inflammatory Diseases and the support of their affiliated NIHR Biomedical Research Centres. Publisher Copyright: © 2019 The Author(s).

PY - 2019/7/15

Y1 - 2019/7/15

N2 - Trial design: We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods: The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study. Conclusions: There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the "at risk" state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration: Current Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014.

AB - Trial design: We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods: The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study. Conclusions: There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the "at risk" state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration: Current Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014.

KW - Abatacept

KW - Antibodies to citrullinated protein antigens

KW - At risk

KW - Autoantibodies

KW - Double-blind

KW - Intervention

KW - Placebo-controlled

KW - Pre-clinical phase

KW - Randomised

KW - Rheumatoid arthritis

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U2 - 10.1186/s13063-019-3403-7

DO - 10.1186/s13063-019-3403-7

M3 - Article

C2 - 31307535

AN - SCOPUS:85069165304

SN - 1745-6215

VL - 20

JO - Trials

JF - Trials

IS - 1

M1 - 429

ER -

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): A multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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