Rheumatoid arthritis prevention with abatacept - long-term outcome study

Plain English Summary

Background and study aims
Rheumatoid arthritis (RA) is an autoimmune, long-term inflammatory disease that causes pain, stiffness, swelling and limited joint movement. RA can affect any joint (most commonly the small joints in the hands and feet) and can develop at any age. The condition can trigger and generate an immune response (e.g. this includes the production of antibodies) that may cause damage to joint tissues and over time may lead to destruction of cartilage and bone. In some patients, the inflammation can affect other organs such as blood vessels, the eyes or lungs. If not effectively treated, the condition may lead to permanent damage to joints and functional disability in people, including limitations to the quality of life.
RA affects more than 500,000 people in the UK. If not treated effectively, the condition leads to joint damage and significant disability. RA is costly to individuals and their families; one third of patients with arthritis stop work within 2 years of onset because of their disease. RA is costly to the UK economy, estimated to be in the region of £5 billion per year, through direct costs to the NHS and associated healthcare providers, and indirect costs associated with early death and loss of productivity.
Disease-modifying anti-rheumatic drugs (DMARDs) have transformed the treatment of RA. Research has shown that this approach leads to higher proportions of patients become symptom-free for long periods. This means they have improved function and joint damage is slowed or even prevented. Intensive treatment of patients with very early RA can mean that some of them can be symptom-free without needing to take medicines. It is important to detect the early signs of RA and to predict which patients are likely to develop severe RA in order to reduce disability and inability to work. People who have mild joint pain can be tested for certain antibodies that are associated with the eventual development of RA.
A previous study called APIPPRA was started in 2013. This study tested whether treatment with a drug called abatacept (Orencia) could prevent development of RA in people who had joint pain and were positive for the antibodies, but did not have the inflammatory signs of RA. Results of this study are expected in early 2021. This study, called ALTO, is following the same participants in APIPPRA on a more long-term basis to investigate whether abatacept treatment prevents or delays additional joints being affected by pain or inflammation.

Who can participate?
Patients enrolled in the APIPPRA study who have completed at least one APIPPRA study visit

What does the study involve?
During the APIPPRA study, participants will have received abatacept or placebo (dummy) injections once weekly for a year and were then followed up without treatment for a further year. In ALTO, they will be assessed every 6 months for a further 3 years.

What are the possible benefits and risks of participating?
ALTO study participants will not receive any study drugs, so there are no risks of side effects as a result of participating. They might benefit from the regular assessment of their condition.

Where is the study run from?
Guy’s and St Thomas’s Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
June 2020 to July 2023

Who is funding the study?
Bristol-Myers Squibb (USA), which sells abatacept

Who is the main contact?
Prof. Andrew Cope (Chief Investigator)
altos@kcl.ac.uk

Trial website

Type

Scientific

Primary contact

Prof Andrew Cope

ORCID ID

http://orcid.org/0000-0001-6735-5496

Contact details

CIBCI
1st floor
New Hunt's House
Guy's Campus
Great Maze Pond
London
SE1 1UL
United Kingdom
+44 (0)2078480852
altos@kcl.ac.uk

EudraCT number

2020-000108-12

ClinicalTrials.gov number

Nil known

Protocol/serial number

IM101-865

Scientific title

Arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept long-term outcome study

Acronym

ALTO

Study hypothesis

The purpose of this study is to capture long-term outcome data from the APIPPRA study to determine whether rheumatoid arthritis (RA) is prevented or delayed when targeted immunotherapy is given to participants in whom autoantibody screening, together with symptoms, indicates a high risk of developing the disease.

Ethics approval

Approval pending

Study design

Long-term follow-up of the APIPPRA study

Primary study design

Observational

Secondary study design

Longitudinal study

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Rheumatoid arthritis

Intervention

Long-term observation of treatment with abatacept.

After consenting, patients are clinically checked and routine blood samples will be taken at each study visit for ESR and CRP to compute disease activity scores. Monitoring for drug toxicity for those study participants who are treated with conventional synthetic and/or biologic DMARDs will be left to the discretion of the supervising rheumatologist. Monitoring may be undertaken at the time of study visits, as part of standard care. There will be no additional blood taken for laboratory studies.

All participants (regardless of their disease status) will remain in the study and complete assessments (two questionnaires) on an approximately 6-monthly basis according to the schedule of visits, including full documentation of treatment for their inflammatory arthritis, where relevant. The final visit will be completed by January 2023.

Intervention type

Drug

Phase

Not Applicable

Drug names

Abatacept

Primary outcome measure

1. Inflammation of the joints assessed by physical examination
2. RA medication (time of commencing DMARD therapy) taken from medical records
Timepoints: assessed at baseline and at every 6 monthly visit for max of 3 years (unless otherwise stated)

Secondary outcome measures

1. Joint damage assessed by X-rays of hands and feet at the final visit
2. Quality of life assessed by Health Assessment Questionnaire (HAQ)
3. Quality of life assessed by Euro-Quality of Life Questionnaire (EQ-5D)
4. Joint damage/inflammation assessed by ultrasound of joints (only when they developed synovitis)
5. Concomitant medication use assessed by recording all concomitant medication
6. Adverse events: important medical events and events of special interest recorded following the participant’s written consent to participate in the study
Timepoints: assessed at baseline and at every 6 monthly visit for max of 3 years (unless otherwise stated)

Overall trial start date

01/06/2020

Overall trial end date

31/07/2023

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Male or female participants, aged ≥18 years
2. All participants deemed eligible and randomised to the APIPPRA study
3. All participants who completed at least one APIPPRA study visit
4. All participants who are willing to consent to the ALTO study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

206

Participant exclusion criteria

1. Participants who are still participating in the APIPPRA study
2. Participants ineligible and randomised to the APIPPRA study in error
3. Participants deemed eligible and randomised to the APIPPRA study but who never received study drug
4. Those unable to give informed consent

Recruitment start date

01/01/2021

Recruitment end date

31/07/2023

Countries of recruitment

Netherlands, United Kingdom

Trial participating centre

Guy's & St Thomas's NHS Foundation Trust
Academic Department of Rheumatology CMCBI, 1st floor, New Hunt's House Guy's Hospital Campus Great Maze Pond
London
SE1 1UL
United Kingdom

Trial participating centre

King's College Hospital NHS Foundation Trust
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

University College London Hospitals NHS Trust
3rd Floor Central 250 Euston Road
London
NW1 2PG
United Kingdom

Trial participating centre

LUMC, Department of Rheumatology
Postzone C1-R Visiting address room D3-49 Albinusdreef 2
Leiden
2333 ZA
Netherlands

Trial participating centre

Basildon and Thurrock University Hospitals NHS Foundation Trust
Basildon and Thurrock University Nethermayne Basildon Hospital
Basildon
SS16 5NL
United Kingdom

Trial participating centre

Cambridge University Hospital NHS Foundation Trust
Rheumatology Clinical Research Unit Box 194, Unit E6 Addenbrooke's Hospital Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Glasgow Royal Infirmary
4 Castle Street
Glasgow
G4 0SF
United Kingdom

Trial participating centre

Newcastle upon Tyne NHS Foundation Trust
Musculoskeletal Research Group Institute of Cellular Medicine Newcastle University 4th floor, Catherine Cookson Building The Medical School Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom

Trial participating centre

Great Western Hospitals NHS Foundation Trust
Great Western Hospital Marlborough Road
SN3 6BB
United Kingdom

Trial participating centre

The Dudley Group Of Hospitals NHS Foundation Trust
Department of Rheumatology Russells Hall Hospital Pensnett Road
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

The University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
New Queen Elizabeth Hospital UHB & City (Birmingham) Rheumatology Research Group 3rd Floor Institute For Biomedical Research Medical School Edgbaston
Birmingham
B15 2TT ‎
United Kingdom

Trial participating centre

Sandwell and West Birmingham Hospitals NHS Trust
Birmingham City Hospital
Birmingham
B18 7QH
United Kingdom

Trial participating centre

The Royal Wolverhampton NHS Trust
Cannock Chase Hospital Rheumatology Department Brunswick Road
Cannock
WS11 5XY
United Kingdom

Trial participating centre

Midlands Partnership NHS Foundation Trust
Haywood Hospital High Lane
Stoke on Trent
ST6 7AG
United Kingdom

Trial participating centre

The Leeds Teaching Hospital NHS Trust
Leeds Institute of Rheumatic & Musculoskeletal Medicine Chapel Allerton Hospital Chapeltown Road
Leeds
LS7 4SA
United Kingdom

Trial participating centre

Central Manchester University Hospitals NHS Foundation Trust
The Kellgren Centre for Rheumatology Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
City Hospital Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Royal Berkshire NHS Foundation Trust
London Road
Reading
RG1 5AN
United Kingdom

Trial participating centre

Countess of Chester Hospital NHS Foundation Trust
Rheumatology Department Liverpool Road
Chester
CH2 1UL
United Kingdom

Trial participating centre

Maidstone & Tunbridge Wells NHS Trust
Maidstone Hospital Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom

Trial participating centre

The Royal Wolverhampton NHS Trust
New Cross Hospital
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

Homerton University Hospital NHS Foundation Trust
Dept of Rheumatology Homerton Hospital
London
E9 6SR
United Kingdom

Trial participating centre

Luton & Dunstable Hospital NHS Foundation Trust
Dept of Rheumatology Luton and Dunstable Hospital Lewsey Road
Luton
LU4 0DZ
United Kingdom

Trial participating centre

Heart of England NHS Foundation Trust
Rheumatology Solihull Hospital Lode Lane
Solihull
B91 2JL
United Kingdom

Trial participating centre

Northampton General Hospital NHS Trust
Cliftonville
Northampton
NN1 5BD
United Kingdom

Trial participating centre

Hull Royal Infirmary
Department of Rheumatology Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

University Hospitals Coventry and Warwickshire NHS Trust
University Hospital of Coventry and Warwickshire Clifford Bridge Rd
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Atrium MC/Zuyderland
Henri Dunantstraat 5
Heerlen
6419 PC
Netherlands

Trial participating centre

Reade
Dr Jan van Breemenstraat 2
Amsterdam
1056 AB
Netherlands

Organisation

Kings College London and Guy's and St Thomas' NHS Foundation Trust

Sponsor details

-
London
SE1 9RT
United Kingdom
+44 (0)20718889811
R&D@gstt.nhs.uk

Sponsor type

University/education

Website

http://www.kcl.ac.uk

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

The results of the trial will be published in a peer-reviewed journal.

IPD sharing statement:
The datasets generated and/or analysed during this study will be included in the subsequent results publication.

Intention to publish date

30/09/2023

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

19/10/2020: The recruitment start date was changed from 01/11/2020 to 01/01/2021. 11/09/2020: The recruitment start date was changed from 01/09/2020 to 01/11/2020 and the contact details were updated. 27/07/2020: The recruitment start date was changed from 01/06/2020 to 01/09/2020. 10/03/2020: This study is a long-term follow-up of participants in the APIPPRA study (ISRCTN46017566).