Rheumatoid arthritis prevention with abatacept - long-term outcome study
ISRCTN | ISRCTN12680338 |
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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
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
Scientific
CIBCI, 1st floor, New Hunt's House
Guy's Campus, Great Maze Pond
London
SE1 1UL
United Kingdom
0000-0001-6735-5496 | |
Phone | +44 (0)2078480852 |
altos@kcl.ac.uk |
Study information
Study design | Long-term follow-up of the APIPPRA study |
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Primary study design | Observational |
Secondary study design | Longitudinal study |
Study setting(s) | Hospital |
Study type | Prevention |
Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
Scientific title | Arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept long-term outcome study |
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(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 |
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 |
Pharmaceutical study type(s) | |
Phase | Not Applicable |
Drug / device / biological / vaccine name(s) | Abatacept |
Primary outcome measure | Current 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 measures | Current 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 date | 01/06/2020 |
Overall study end date | 30/07/2024 |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Lower age limit | 18 Years |
Sex | Both |
Target number of participants | 206 |
Total final enrolment | 143 |
Participant inclusion criteria | Current 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 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 | 26/04/2021 |
Recruitment end date | 31/07/2023 |
Locations
Countries of recruitment
- England
- Netherlands
- Scotland
- United Kingdom
Study participating centres
CMCBI, 1st floor, New Hunt's House
Guy's Hospital Campus
Great Maze Pond
London
SE1 1UL
United Kingdom
London
SE5 9RS
United Kingdom
250 Euston Road
London
NW1 2PG
United Kingdom
Visiting address room D3-49
Albinusdreef 2
Leiden
2333 ZA
Netherlands
Nethermayne
Basildon Hospital
Basildon
SS16 5NL
United Kingdom
Box 194, Unit E6
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Glasgow
G4 0SF
United Kingdom
Institute of Cellular Medicine
Newcastle University
4th floor, Catherine Cookson Building
The Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom
Marlborough Road
SN3 6BB
United Kingdom
Russells Hall Hospital
Pensnett Road
Dudley
DY1 2HQ
United Kingdom
Rheumatology Research Group
3rd Floor
Institute For Biomedical Research
Medical School
Edgbaston
Birmingham
B15 2TT
United Kingdom
Birmingham
B18 7QH
United Kingdom
Rheumatology Department
Brunswick Road
Cannock
WS11 5XY
United Kingdom
High Lane
Stoke on Trent
ST6 7AG
United Kingdom
Chapel Allerton Hospital
Chapeltown Road
Leeds
LS7 4SA
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Reading
RG1 5AN
United Kingdom
Liverpool Road
Chester
CH2 1UL
United Kingdom
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom
Wolverhampton
WV10 0QP
United Kingdom
Homerton Hospital
London
E9 6SR
United Kingdom
Luton and Dunstable Hospital
Lewsey Road
Luton
LU4 0DZ
United Kingdom
Solihull Hospital
Lode Lane
Solihull
B91 2JL
United Kingdom
Northampton
NN1 5BD
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Clifford Bridge Rd
Coventry
CV2 2DX
United Kingdom
Heerlen
6419 PC
Netherlands
Amsterdam
1056 AB
Netherlands
Sponsor information
University/education
-
London
SE1 9RT
England
United Kingdom
Phone | +44 (0)20718889811 |
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R&D@gstt.nhs.uk | |
Website | http://www.kcl.ac.uk |
Funders
Funder type
Other
No information available
Results and Publications
Intention to publish date | 01/07/2025 |
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Individual participant data (IPD) Intention to share | No |
IPD sharing plan summary | Stored in repository |
Publication and dissemination plan | The results of the trial will be published in a peer-reviewed journal. |
IPD sharing plan | The 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? |
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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).