Rheumatoid arthritis prevention with abatacept - long-term outcome study

ISRCTN ISRCTN12680338
DOI https://doi.org/10.1186/ISRCTN12680338
EudraCT/CTIS number 2020-000108-12
IRAS number 270373
Secondary identifying numbers IM101-865, IRAS 270373
Submission date
05/03/2020
Registration date
09/04/2020
Last edited
05/12/2024
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

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 the 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 becoming 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 the 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 2024

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

Contact information

Prof Andrew Cope
Scientific

CIBCI, 1st floor, New Hunt's House
Guy's Campus, Great Maze Pond
London
SE1 1UL
United Kingdom

ORCiD logoORCID ID 0000-0001-6735-5496
Phone +44 (0)2078480852
Email altos@kcl.ac.uk

Study information

Study designLong-term follow-up of the APIPPRA study
Primary study designObservational
Secondary study designLongitudinal study
Study setting(s)Hospital
Study typePrevention
Participant information sheet Not available in web format, please use contact details to request a participant information sheet
Scientific titleArthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept long-term outcome study
Study acronymALTO
Study hypothesisThe 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(s)Approved 05/03/2021, London -South East Research Ethics Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)207 104 8085; londonsoutheast.rec@hra.nhs.uk), ref: 21/LO/0035
ConditionRheumatoid arthritis
InterventionLong-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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Abatacept
Primary outcome measureCurrent primary outcome measures as of 20/07/2021:
For those participants who met the APIPPRA primary endpoint during the APIPPRA study, this will be their primary endpoint in the ALTO study. For those study participants who did not meet the primary endpoint during the APIPPRA study, the primary endpoint in the ALTO study is the time from randomisation in the APIPPRA study to the development of clinical synovitis or RA defined by one of the following events, whichever is met first:
1. The development of clinically apparent synovitis in ≥3 joints, as determined by an assessor with experience in clinical assessment of RA
2. The development of RA according to the ACR/EULAR 2010 criteria, where joint involvement is defined as joint swelling
3. The prescription of first DMARD (e.g. methotrexate or equivalent) by a rheumatologist

Previous primary outcome measures:
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 measuresCurrent secondary outcome measures as of 20/07/2021:
1. The development of RA when imaging assessments are included, measured using tender and swollen joint counts and ultrasound, captured retrospectively then at baseline and every 6 months thereafter until 31/01/2023
2. Disease activity and progression over time, assessed using DAS28 (tender and swollen joint counts, patient global visual analogue score (VAS), CRP and ESR and Extended Joint Count 68/66, Simple Disease Activity Score (SDAI) and Clinical Disease Activity Score (CDAI), Pain VAS, Health Assessment Questionnaire (HAQ), Euro-Quality of Life Questionnaire (EQ-5D-3L), captured retrospectively then at baseline and every 6 months thereafter until 31/01/2023
3. The proportion of participants requiring conventional synthetic DMARD (csDMARD) therapy, and the time to commencing oral or parenteral corticosteroids, measured using clinical visits and electronic health records, captured retrospectively then at baseline and every 6 months thereafter until 31/01/2023
4. The proportion of participants requiring biologic DMARD therapy, and the time to commencing biologic DMARD therapy, measured using clinical visits and electronic health records captured retrospectively then at baseline and every 6 months thereafter until 31/01/2023
5. Radiographic changes in X-rays of the hands and feet from enrolment in APIPPRA to the end of ALTO, scored by van der Heijde Sharp Modified Scores at final visit by 31/01/2023
6. Safety, with emphasis on serious adverse events and events of special interest such as cardiovascular events, infection and cancer, assessed using clinical visits and electronic health records, captured retrospectively then at baseline and every 6 months thereafter until 31/01/2023

Previous 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 study start date01/06/2020
Overall study end date30/07/2024

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants206
Total final enrolment143
Participant inclusion criteriaCurrent inclusion criteria as of 20/07/2021:
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 give written informed consent and comply with the requirements of the ALTO study protocol.

Previous 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 exclusion criteria1. 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 date26/04/2021
Recruitment end date31/07/2023

Locations

Countries of recruitment

  • England
  • Netherlands
  • Scotland
  • United Kingdom

Study participating centres

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
King's College Hospital NHS Foundation Trust
Denmark Hill
London
SE5 9RS
United Kingdom
University College London Hospitals NHS Trust
3rd Floor Central
250 Euston Road
London
NW1 2PG
United Kingdom
LUMC, Department of Rheumatology
Postzone C1-R
Visiting address room D3-49
Albinusdreef 2
Leiden
2333 ZA
Netherlands
Basildon and Thurrock University Hospitals NHS Foundation Trust
Basildon and Thurrock University
Nethermayne
Basildon Hospital
Basildon
SS16 5NL
United Kingdom
Cambridge University Hospital NHS Foundation Trust
Rheumatology Clinical Research Unit
Box 194, Unit E6
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Glasgow Royal Infirmary
4 Castle Street
Glasgow
G4 0SF
United Kingdom
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
Great Western Hospitals NHS Foundation Trust
Great Western Hospital
Marlborough Road
SN3 6BB
United Kingdom
The Dudley Group Of Hospitals NHS Foundation Trust
Department of Rheumatology
Russells Hall Hospital
Pensnett Road
Dudley
DY1 2HQ
United Kingdom
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
Sandwell and West Birmingham Hospitals NHS Trust
Birmingham City Hospital
Birmingham
B18 7QH
United Kingdom
The Royal Wolverhampton NHS Trust
Cannock Chase Hospital
Rheumatology Department
Brunswick Road
Cannock
WS11 5XY
United Kingdom
Midlands Partnership NHS Foundation Trust
Haywood Hospital
High Lane
Stoke on Trent
ST6 7AG
United Kingdom
The Leeds Teaching Hospital NHS Trust
Leeds Institute of Rheumatic & Musculoskeletal Medicine
Chapel Allerton Hospital
Chapeltown Road
Leeds
LS7 4SA
United Kingdom
Central Manchester University Hospitals NHS Foundation Trust
The Kellgren Centre for Rheumatology
Oxford Road
Manchester
M13 9WL
United Kingdom
Nottingham University Hospitals NHS Trust
City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Royal Berkshire NHS Foundation Trust
London Road
Reading
RG1 5AN
United Kingdom
Countess of Chester Hospital NHS Foundation Trust
Rheumatology Department
Liverpool Road
Chester
CH2 1UL
United Kingdom
Maidstone & Tunbridge Wells NHS Trust
Maidstone Hospital
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom
The Royal Wolverhampton NHS Trust
New Cross Hospital
Wolverhampton
WV10 0QP
United Kingdom
Homerton University Hospital NHS Foundation Trust
Dept of Rheumatology
Homerton Hospital
London
E9 6SR
United Kingdom
Luton & Dunstable Hospital NHS Foundation Trust
Dept of Rheumatology
Luton and Dunstable Hospital
Lewsey Road
Luton
LU4 0DZ
United Kingdom
Heart of England NHS Foundation Trust
Rheumatology
Solihull Hospital
Lode Lane
Solihull
B91 2JL
United Kingdom
Northampton General Hospital NHS Trust
Cliftonville
Northampton
NN1 5BD
United Kingdom
Hull Royal Infirmary
Department of Rheumatology
Anlaby Road
Hull
HU3 2JZ
United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
University Hospital of Coventry and Warwickshire
Clifford Bridge Rd
Coventry
CV2 2DX
United Kingdom
Atrium MC/Zuyderland
Henri Dunantstraat 5
Heerlen
6419 PC
Netherlands
Reade
Dr Jan van Breemenstraat 2
Amsterdam
1056 AB
Netherlands

Sponsor information

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

-
London
SE1 9RT
England
United Kingdom

Phone +44 (0)20718889811
Email R&D@gstt.nhs.uk
Website http://www.kcl.ac.uk

Funders

Funder type

Other

Investigator initiated and funded

No information available

Results and Publications

Intention to publish date01/07/2025
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryStored in repository
Publication and dissemination planThe results of the trial will be published in a peer-reviewed journal.
IPD sharing planThe datasets generated and/or analysed during this study will be included in the subsequent results publication.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No

Editorial Notes

05/12/2024: The overall study end date was changed from 31/07/2023 to 30/07/2024. The intention to publish date was changed from 31/12/2024 to 01/07/2025.
19/03/2024: Total final enrolment added. The intention to publish date was changed from 30/09/2023 to 31/12/2024.
19/10/2022: Ethics approval details added.
20/07/2021: The inclusion criteria and primary and secondary outcomes were updated. The recruitment start date was changed from 01/01/2021 to 26/04/2021.
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).