Can we predict which patients with psoriatic arthritis will respond to treatment using precision medicine?
| ISRCTN | ISRCTN17228602 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17228602 |
| IRAS number | 287528 |
| Secondary identifying numbers | CPMS 48066, IRAS 287528 |
- Submission date
- 03/03/2021
- Registration date
- 23/03/2021
- Last edited
- 06/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
Psoriatic arthritis (PsA) is a type of arthritis that affects some people with the skin condition psoriasis. It typically causes affected joints to become swollen, stiff and painful.
PsA is an inflammatory arthritis that develops in around 15% of people with psoriasis, causing swollen and painful joints. For patients who do not respond to standard arthritis drugs, two classes of biologic drugs are available (TNF or IL-17 blockers). A similar proportion of patients respond to both with around 50% achieving a good response. However, we do not know how to predict which patient will respond best to each drug.
Our aim is to test whether we can predict if people with psoriatic arthritis (PsA) will respond to certain biologic drugs using blood tests. We will test if high levels of a type of T cells (activated Th17 cells) or other laboratory tests predict response. We will use statistical tests to estimate how effective these approaches would be for each individual. If successful, this approach could ensure that patients receive their best option first, ensuring their disease is controlled and quality of life improved, while avoiding unnecessary drug use. This is likely to save money for the NHS.
Who can participate?
Patients aged 18 years or older, with PsA about to start their first biologic treatment will be invited to join the study.
What does the study involve?
Participants will have a blood sample taken to measure their activated Th17 cells. The patients will be allocated to receive either TNF or IL-17 blocking biologics. We will measure how well they respond after 6 months of treatment and test whether the initial blood test result could have predicted their response.
What are the possible benefits and risks of participating?
Participants are not expected to benefit directly from participating in the study however they should see an improvement in their PsA symptoms from the treatment they receive. Study visits have been aligned with routine NHS visits to minimise burden and inconvenience but will take longer and participants will be asked to complete extra questionnaires. Participants will need to have additional blood samples taken which may result in bruising but research samples will be taken at the same time as routine NHS blood tests wherever possible.
Participants at 3 sites (Oxford, Glasgow, & St Guys & St Thomas's) will be asked to attend a short additional visit to enable the collection of an additional blood sample. Travel costs will be reimbursed for this additional visit to minimise any financial burden.
There are no additional risks from the treatment as the study uses the same treatments that would be prescribed routinely for these patients.
Where is the study run from?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
February 2021 to September 2026
Who is funding the study?
National Institute for Health Research (NIHR) (UK).
Who is the main contact?
Dr Laura Coates, laura.coates@ndorms.ox.ac.uk
Contact information
Scientific
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford
Botnar Research Centre
Windmill Road
Oxford
OX3 7LD
United Kingdom
| Phone | +44 (0)1865 737838 |
|---|---|
| laura.coates@ndorms.ox.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Optimising Psoriatic Arthritis Therapy with Immunological Methods to Increase Standard Evaluation |
| Study acronym | OPTIMISE |
| Study hypothesis | A precision choice of bDMARDs in PsA based on lymphocyte cell surface markers guiding selection of either TNF inhibitor or IL17A inhibitor will give superior results to patients having a choice of bDMARD based on clinical characteristics alone. |
| Ethics approval(s) | Approved 24/02/2021, North West - Preston REC (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)207 104 8206; Preston.rec@hra.nhs.uk), ref: 21/NW/0016 |
| Condition | Arthritis that affects some people with the skin condition psoriasis |
| Intervention | All patients will be treated with a biologic drug (TNF inhibitors (adalimumab) or IL-17A inhibitors (secukinumab) in keeping with routine clinical practice. At present both TNF inhibitors and IL-17 inhibitors are licensed and NICE approved as first line biologics in PsA. Patients will be randomised in a 1:1 ratio to receive either TNF or IL-17A inhibitors, stratified by baseline immunophenotype, for 24 weeks. The TNF inhibitor to be used is adalimumab (any brand) and it is to be given at the usual licensed dose, as per the SmPC: -The licenced dose of adalimumab for psoriatic arthritis is always 40 mg by subcutaneous injection every 2 weeks, with no loading doses. The IL-17A inhibitor to be used is secukinumab, brand name Cosentyx, and is to be given at the usual licensed dose as per the SmPC: -The licensed dose of secukinumab for psoriatic arthritis varies based on the level of baseline skin psoriasis. For patients with concomitant moderate to severe plaque psoriasis, the recommended dose is 300mg by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3 and 4 followed by a monthly maintenance dose. For other patients the recommended dose is 150mg by subcutaneous injection at the same timepoints. This study will follow routine practice and the current label by using the appropriate dose of secukinumab based on the baseline psoriasis disease activity with the cut off for moderate to severe psoriasis as 10% body surface area. Dose escalation as per the licence is permitted. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Adalimumab, secukinumab |
| Primary outcome measure | Clinical response as measured by the minimal disease activity (MDA) criteria at baseline and week 24 |
| Secondary outcome measures | 1. Clinical disease pattern at baseline measured by the minimal disease activity (MDA) criteria 2. Immunophenotype data at baseline measuring activated Th17 and intracellular levels of IL-17 3. Activated Th17 proportion and intracellular levels of IL-17 at baseline and week 24 4. Clinical response as measured by the minimal disease activity (MDA) criteria at week 12/16 and week 24 5. Cell-specific transcriptomic data and whole blood transcriptomes from samples collected at baseline and week 24 |
| Overall study start date | 01/02/2021 |
| Overall study end date | 30/09/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 424; UK Sample Size: 424 |
| Participant inclusion criteria | Current inclusion criteria as of 15/08/2022: 1. Participant is willing and able to give informed consent for participation in the study 2. Male or female, age 18 years or over 3. Diagnosis of PsA confirmed by the CASPAR criteria 4. Is planned to have biologic therapy for psoriatic arthritis using NICE/SMC criteria (failure of ≥2 csDMARDs and ≥3 tender and ≥3 swollen joints) _____ Previous inclusion criteria: 1. Participant is willing and able to give informed consent for participation in the study 2. Male or female, age 18 years or over 3. Diagnosis of PsA confirmed by the CASPAR criteria 4. Is planned to have biologic therapy for psoriatic arthritis using NICE/SMC criteria (failure of >=2 csDMARDs and >=3 tender/swollen joints) |
| Participant exclusion criteria | 1. Contraindications to either TNF inhibitor or secukinumab: 1.1. History of previous demyelinating disease including multiple sclerosis 1.2. Heart failure (NYHA class 3 or 4) 1.3. Serious infections: active tuberculosis (TB), chronic viral infections (including hepatitis B, C and HIV), recent serious bacterial infections 1.4. Latent TB unless they have received appropriate anti-tuberculous treatment as per local guidelines 1.5. Active symptomatic inflammatory bowel disease 1.6. History of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ 1.7. Hypersensitivity to active ingredient or excipients 2. Current or previous treatment with biologic DMARDs or targeted synthetic DMARDs 3. Use of investigational therapies within 1 month or 5 half-lives (whichever is longer) of baseline 4. Women who are pregnant, lactating or planning pregnancy during the following 12 months |
| Recruitment start date | 01/01/2022 |
| Recruitment end date | 31/12/2024 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Headley Way
Oxford
OX3 9DU
United Kingdom
London
SE1 7EH
United Kingdom
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom
Corporation Street
Stafford
ST16 3SR
United Kingdom
Coventry
CV2 2DX
United Kingdom
Woodlands House
2nd Floor
Maes y Coed Rd
Heath Park
Cardiff
CF14 4HH
United Kingdom
London Road
Reading
RG1 5AN
United Kingdom
Bath
BA1 3NG
United Kingdom
London
SE5 9RS
United Kingdom
London
SW17 0QT
United Kingdom
Sponsor information
University/education
Joint Research Office, 1st Floor, Boundary Brook House
Churchill Drive
Oxford
OX3 7GB
England
United Kingdom
| ctrg@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
No information available
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/09/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | The participant-level data set and statistical code will be available upon reasonable request from Laura Coates (laura.coates@ndorms.ox.ac.uk) and the Oxford Clinical Trials Research Unit (OCTRU; octrutrialshub@ndorms.ox.ac.uk) once the study findings have been published in full and for as long as this data is useful. Consent has been provided consent to share with the funder and other researchers based at hospitals, universities, non-profit institutions or commercial laboratories worldwide; however, some specific data items may not be shared in order to maintain participant anonymity. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 28/03/2023 | 29/09/2023 | Yes | No | |
| Protocol file | version 8.0 | 07/11/2023 | 08/11/2023 | No | No |
Additional files
Editorial Notes
06/12/2024: The study contact confirmed that the study dates were correct.
08/11/2023: The following changes were made to the study record:
1. Protocol file uploaded.
2. The recruitment end date was changed from 30/11/2023 to 31/12/2024.
3. The overall study end date was changed from 30/11/2024 to 30/09/2026.
4. The intention to publish date was changed from 01/11/2025 to 01/09/2026.
29/09/2023: Publication reference added.
21/08/2023: The IPD sharing statement has been added.
02/06/2023: The recruitment end date has been changed from 30/06/2023 to 30/11/2023.
15/08/2022: The following changes have been made:
1. The recruitment end date has been changed from 01/02/2023 to 30/06/2023.
2. The participant inclusion criteria have been changed.
20/10/2021: The recruitment start date has been changed from 01/07/2021 to 01/01/2022.
03/03/2021: Trial's existence confirmed by the National Institute for Health Research (NIHR) (UK).
