OPtimising Treatment with Tumour necrosis factor (TNF) Inhibitors in Rheumatoid Arthritis: is dose tapering practical in good responders?
| ISRCTN | ISRCTN28955701 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN28955701 |
| EudraCT/CTIS number | 2010-020738-24 |
| Secondary identifying numbers | OPTTIRA Protocol - Version 1.1 - 14.09.10 |
- Submission date
- 24/11/2010
- Registration date
- 25/05/2011
- Last edited
- 06/06/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Not provided at time of registration
Contact information
Prof David Scott
Scientific
Scientific
King's Musculoskeletal Clinical Trials Unit
Department of Academic Rheumatology
King's College London
Weston Education Centre
Cutcombe Road
Denmark Hill
London
SE5 9RJ
United Kingdom
| d.scott1@nhs.net |
Study information
| Study design | Randomised controlled open-label multicentre proof of principle trial followed by an open exploratory phase trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | OPtimising Treatment with Tumour necrosis factor (TNF) Inhibitors in Rheumatoid Arthritis: is dose tapering practical in good responders? A 'proof of principle' and exploratory trial |
| Study acronym | OPTTIRA |
| Study hypothesis | Our hypothesis is that tapering TNF inhibitors (to a minimum of one third of the initial induction doses) will not adversely affect disease control in established RA patients who have achieved a good response to standard doses of TNF inhibitors and are also receiving disease modifying anti-rheumatic drugs (DMARDs). We consider an increase of disease activity score (DAS28) at least 0.6 represents a clinical important change. |
| Ethics approval(s) | North West London REC 2, 12/10/2010, ref: 10/H0720/69 |
| Condition | Rheumatoid arthritis |
| Intervention | Patients will be randomised to one of three tapering groups: 1. Experimental group 1: patients have their TNF inhibitor tapered to 66% of initial dose by reducing frequency of dosing 2. Experimental group 2: patients have their TNF inhibitor tapered to 33% of initial dose by reducing frequency of dosing 3. Control group: patients continue on standard doses If the proof of principle phase supports TNF inhibitor tapering, patients will enter an exploratory extension study. Progression to the Exploratory phase for Experimental groups 1 and 2 will be based on the patient level eligibility criteria to ensure that it is appropriate for the patient to continue tapering. The Proof of Principle Control Group will have their TNF inhibitors tapered over 6 months to either 66% or 33% by reducing the frequency of their injections. Patients originally in the tapering groups will have their TNF inhibitors reduced further over 6 months by increasing the time between injections on each occasion until they are stopped completely. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | The development of flares, defined as an increase in DAS28 scores at least 0.6. To ensure such changes in DAS28 represent a genuine flare in RA and are not due to unrelated events (e.g. an inter-current illness like influenza) additional criteria required for a flare are: 1. It must include an increase in the swollen joint count 2. It must be present on two occasions at least one week apart 3. It results in DAS28 scores greater than 3.2 Large increases in DAS28 scores (1.2 or more) which result in DAS28 greater than 3.2 will not require any additional criteria. DAS28 measurements at baseline, 3, 6, 9 and 12 monthly assessments. The participants will also be telephoned every month to check whether their RA symptoms have increased. If it is suspected a patient is experiencing a flare, they should come in for a flare assessment within 2 weeks. |
| Secondary outcome measures | 1. DAS28 [tender and swollen joint counts, patient global Visual Analogue Scale (VAS), erythrocyte sedimentation rate (ESR)] and Extended Joint Count 68/66, monitored at baseline, 3, 6, 9 and 12 months 2. Simple disease activity score (SDAI) and clinical disease activity score (CDAI), at baseline, 3, 6, 9 and 12 months 3. Health Assessment Questionnaire (HAQ) scores, at baseline, 3, 6, and 12 months 4. Adverse events, at baseline, 3, 6, 9 and 12 months 5. EuroQol scores, at baseline, 3, 6, and 12 months 6. SF-36, at baseline, 3, 6, and 12 months 7. Plain x-rays of the hands and feet scored by Larsens and Van Der Heijdi Sharpe Modified Scores (to provide preliminary data), at baseline, 6, and 12 months 8. Analysis of serum, immunological and gene expression profiles; biomarker blood taken at baseline for the experimental groups and at 6 months for the control group |
| Overall study start date | 14/12/2010 |
| Overall study end date | 31/08/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 99 |
| Participant inclusion criteria | 1. RA by American College of Rheumatology and EULAR criteria 2. Etanercept or adalimumab treatment for at least 6 months (a break of up to 4 consecutive weeks is permitted) 3. Taking at least one DMARD 4. Stable clinical response for at least 3 months (one DAS28 score of 3.2 or less; no increase in DAS28 greater than 0.6) 5. Patient considers he or she has achieved a suitable response to TNF inhibitors 6. Supervising rheumatologist considers further improvements are unlikely on the patients current treatment regimen 7. At least 18 years of age, either sex 8. Willing and able to give informed consent |
| Participant exclusion criteria | 1. Serious concurrent illness (e.g. terminal cancer) 2. Prednisolone at more than 10mg daily (for doses > 10mg daily, a 4 week washout period is required) 3. Recently received intramuscular (IM)/intra-areterial (IA) steroids (12 weeks washout required) 4. Pregnancy, breast-feeding or women of child-bearing potential not using adequate contraception |
| Recruitment start date | 14/12/2010 |
| Recruitment end date | 31/08/2013 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
King's College London
London
SE5 9RJ
United Kingdom
SE5 9RJ
United Kingdom
Sponsor information
King's College London (KCL) (UK)
University/education
University/education
The Strand
London
WC2R 2LS
England
United Kingdom
| Website | http://www.kcl.ac.uk/index.aspx |
|---|---|
"ROR" |
https://ror.org/0220mzb33 |
Funders
Funder type
Charity
Arthritis Research UK (UK)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/11/2017 | Yes | No | |
| Results article | results | 17/05/2018 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
06/06/2018: Publication reference added.
03/10/2017: Publication reference added.
