Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Tocilizumab, anti-TNF treatment
Brief summary
To compare the efficacy of switching to a different molecular target (from TNF to IL6) versus cycling to a second TNF inhibitor in patients with active RA, who have not adequately responded to a previous treatment with a first anti-TNF.
Detailed description
New drugs for the treatment of rheumatoid arthritis (RA) with action on specific molecular target (e.g. anti-TNF) have improved the prognosis of patients with an inadequate response to conventional therapy such as methotrexate (MTX). However, approximately 50% of patients treated with first-line anti-TNF discontinue treatment after two years due to ineffectiveness or adverse events. The second line treatment involves the use of another anti-TNF drug or switching to a different molecular target (anti-IL6, -CD20 or CTLA-4-Ig) in combination with MTX.
Interventions
DRUGTocilizumab
8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days
DRUGEtanercept
a. Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab
DRUGInfliximab
infliximab if initial failure to the receptor fusion protein, etanercept.
DRUGAdalimumab
adalimumab if initial failure to the receptor fusion protein, etanercept.
DRUGGolimumab
golimumab if initial failure to the receptor fusion protein, etanercept.
DRUGCertolizumab Pegol
Certolizumab Pegol if initial failure to the receptor fusion protein, etanercept.
Sponsors
Mario Negri Institute for Pharmacological Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at the time of signing the informed consent form and either male or female. * Diagnosis of RA according to the 1987 ACR classification criteria OR 2010 ACR/EULAR classification criteria at least 6 months prior to screening. * Patients with persistent RA disease activity whilst being treated with an initial TNFi agent on a background MTX up to 20-25 mg/week for at least 12 weeks defined according to SIR and EULAR guidelines as: primary non-response: failing to improve DAS28 by ≥ 1.2 or failing to achieve DAS28 ≤ 3.2 within the first three to six months of starting the initial TNFi; secondary non-response: determined by physician decision with evidence of flare and deterioration in DAS28 of ≥ 1.2. * Methotrexate (MTX) dose stable for 28 days prior to screening. * Patients on NSAIDs and / or corticosteroids must remain on an unchanged regimen for at least 28 days prior to study drug administration. * The patient must be able to comply with the study visit schedule and other protocol requirements. * The patient understands the purpose of the study and is able and willing to sign the informed consent form, according to ICH/GCP. * Signed written informed consent for biological analysis. * Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to start of trial. Women of childbearing potential and male patients must be willing to practice acceptable methods of contraception during treatment and for 6 months (female patients) and 3 months (male patients) after discontinuation of treatment.
Exclusion criteria
* Patients who have previously received more than 1 TNFi drug OR any other biological therapy. * Patients with inflammatory joint disease of different origin or any arthritis with onset prior to 16 years of age. * Patients taking any disease-modifying antirheumatic drug (DMARDs) (e.g. all except methotrexate). Discontinuation must occur at least 28 days prior to study treatment start. * History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug. * Known hypersensitivity to any active substance or excipients of study drug. * Pregnancy or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with good EULAR | 24 weeks | the proportion of patients with good EULAR response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with a good/moderate EULAR | 12 weeks | Proportion of patients with a good/moderate EULAR response |
| Proportion of patients with ACR20/50/70 response | 12 weeks | Proportion of patients with ACR20/50/70 response |
| Proportion of patients with a remission according to DAS28/SDAI/CDAI | 24 weeks | Proportion of patients with a remission according to DAS28/SDAI/CDAI |
| Van Der Heijde Modified Total Sharp Score [X-ray score] | 48 weeks | Van Der Heijde Modified Total Sharp Score \[X-ray score\] |
| Health Assessment Questionnaire (HAQ) score | 24 weeks | Health Assessment Questionnaire (HAQ) score |
Countries
Italy
Outcome results
None listed