Switching to alternative tumour-necrosis factor (TNF)-blocking drugs or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-blocking drug
- Conditions
- Rheumatoid arthritisMusculoskeletal Diseases
- Registration Number
- ISRCTN89222125
- Lead Sponsor
- niversity of Leeds (UK)
- Brief Summary
2014 Protocol article in http://www.ncbi.nlm.nih.gov/pubmed/25539805 protocol 2018 Results article in https://www.ncbi.nlm.nih.gov/pubmed/29900829 results 2020 Results article in https://pubmed.ncbi.nlm.nih.gov/32859608/ results (added 02/09/2020)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 122
Current inclusion criteria as of 03/04/2014:
Patients meeting all of the following criteria will be considered for enrolment into the study:
1. Male and female subjects aged =18 years at the time of signing the Informed Consent Form.
2. Patients with a diagnosis of rheumatoid arthritis as per the ACR/EULAR 2010 classification criteria confirmed at least 24 weeks prior to the screening visit.
3. Patients who have failed conventional DMARD therapy as per NICE/BSR Guidelines i.e. failure of at least two DMARDS including MTX.
4. Patients with persistent RA disease activity despite having been treated with a current initial TNFi agent for at least 12 weeks. Active RA defined as (these criteria are consistent with BSR guidelines):
4.1. Primary non-response: failing to improve DAS28 by > 1.2 or failing to achieve DAS28 = 3.2 within the first 12 to 24 weeks of starting the initial TNFi. This may include patients that have shown a reduction in DAS28 of > 1.2 but still demonstrate unacceptably high disease activity in the physician?s judgement with evidence of an overall DAS28 of = 3.2
OR
4.2. Secondary non-response: defined as inefficacy to first TNFi (having demonstrated prior satisfactory response) as per clinician judgement; with intolerance not the reason for cessation of first TNFi.
5. MTX dose stable for 4 weeks prior to the screening visit and to be continued for the duration of the study.
6. Patients on NSAIDs and/or corticosteroids (oral prednisolone not exceeding 10 mg daily) who have been on an unchanged regimen for at least 4 weeks prior to the screening visit and are expected to remain on a stable dose until the baseline assessments have been completed.
7. Provided written informed consent prior to any trial-specific procedures.
Previous inclusion criteria:
Subjects meeting all of the following criteria will be considered for enrolment into the study:
1. Male and female patients aged over 18 years
2. Diagnosis of rheumatoid arthritis (1987 revised American College of Rheumatology [ACR] criteria) confirmed at least 6 months prior to screening
3. Patients that have exhausted conventional disease modifying anti-rheumatic drugs (DMARD) options (including methotrexate [MTX])
4. Patients with persistent RA disease activity whilst being treated with a TNFi agent for at least 12 weeks defined as:
4.1. Primary non-response: failing to improve 28-item Disease Activity Score (DAS-28) by greater than or equal to 1.2 within the first three months
4.2. Secondary non-response: determined by physician decision with evidence of flare and deterioration in DAS28 of greater than or equal to 1.2 (having previously demonstrated a response to the TNFi)
5. MTX dose stable for 12 weeks prior to screening and to be continued for the duration of the study
6. Patients on non-steriodal anti-inflammatory drugs (NSAIDs) and/or corticosteroids must have remained on an unchanged regimen for at least 28 days prior to study drug administration
7. Patients must be able and willing to comply with the terms of this protocol
Current exclusion criteria as of 03/04/2014:
Patients will be excluded from this study for any of the following reasons:
General
1. Major surgery (including joint surgery) within 8 weeks prior to the screening visit or planned major surgery within 52 weeks following randomization.
Study Specific
2. Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter?s syndrome, psoriatic arthritis, systemic lupus erythematosus, or any arthritis with onset prior to 16 years of age.
3. Patients receiving doses of prednisolone > 10 mg/day within the 4 weeks prior to the screening visit.
4. Patients receiving intra-articular or intra-muscular steroid injections within 4 weeks prior to the screening visit.
Excluded Previous or Concomitant Therapy:
5. Patients who have previously received more than one TNFi drug OR any other biological therapy for the treatment of RA.
6. Patients unable or unwilling to stop treatment with a prohibited DMARD (i.e synthetic DMARD aside from MTX e.g. oral or injectable gold, chloroquine, hydroxychloroquine, cyclosporine, azathioprine, leflunomide, sulphasalazine) prior to the start of protocol treatment.
7. Treatment with any investigational drug in the last 12 weeks prior to the start of protocol treatment.
Exclusions for general safety
These criteria should be considered in the context of BSR guidance.
8. Patients with other co-morbidity including acute, severe infections, uncontrolled diabetes, uncontrolled hypertension, unstable ischaemic heart disease, moderate/severe heart failure (Class III/IV of the New York Heart Association [NYHA] functional classification system), active bowel disease, active peptic ulcer disease, recent stroke (within 12 weeks before the screening visit), or any other condition which, in the opinion of the investigator, would put the patient at risk to participate in the study or would make implementation of the protocol difficult.
9. Patients with any major episode of infection requiring hospitalisation or treatment with IV antibiotics within 12 weeks of start of treatment protocol or oral antibiotics within 4 weeks of start of protocol treatment.
10. Patients at significant risk of infection, which in the opinion of the investigator would put the patient at risk to participate in the study (e.g. leg ulceration, indwelling urinary catheter, septic joint within 52 weeks [or ever if prosthetic joint still in situ]).
11. Patients with known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections including herpes zoster (for tuberculosis and hepatitis B and C see below), but excluding fungal infections of nail beds as per clinical judgment.
12. Patients with untreated active current or latent tuberculosis (TB). Patients should have been screened for latent TB (as per BSR guidelines) within 24 weeks prior to the screening visit and, if positive, treated following local practice guidelines prior to the start of protocol treatment.
13. Patients with active current hepatitis B and/or C infection. Patients should have been screened for hepatitis B and C within 24 weeks prior to the screening visit and
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Current primary outcome measures as of 03/04/2014:<br> Change in Disease Activity Score 28 (DAS28) at 6 months (24 weeks)<br><br> Previous primary outcome measures:<br> Proportion of patients who achieve a reduction in DAS28 of at least 1.2 at 6 months with no toxicity<br>
- Secondary Outcome Measures
Name Time Method