RHEUMATOID ARTHRITIS MedDRA version: 20.0 Level: LLT Classification code 10037738 Term: R arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 20.0 Level: LLT Classification code 10039014 Term: Rh arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue dis
Conditions
Interventions
Trade Name: ROACTEMRA - 20 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) 4ML 1 FLACONCINO
Product Name: Tocilizumab
Product Code: [NA]
Pharmaceutical Form: Concen
Sponsors
SOCIETA' ITALIANA DI REUMATOLOGIA - SIR
Eligibility
Sex/Gender
All
Inclusion criteria
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: A) 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; B) Secondary non-response: determined by physician decision with evidence of flare and deterioration in DAS28 of = 1.2 C) Drug withdrawal for adverse events (not contraindicating a second course of TNFi (not class-adverse events)) - 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 pregnancy test within 7 days prior to start of trial. Women of childbearing potential and male patients must be willing to adopt practice acceptable methods of highly effective contraception measures during treatment and for 6 months (female patients) and 3 months (male patients) after discontinuation of treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
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 |
|---|---|
| Main Objective: 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. ;Secondary Objective: To compare the effect of switching versus cycling on clinical remission, radiological progression, functional disability, pain intensity and health related quality of life; To undertake an evaluation of the cost-effectiveness of switching patients to an alternative-mechanism (anti-IL6) versus cycling to another anti-TNF; To assess the safety profile for the treatment in study, evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, and by the incidence of serious adverse events (SAEs), expected and unexpected.;Primary end point(s): the proportion of patients with good EULAR response at 24 weeks.;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of patients with a good/moderate EULAR (European League Against Rheumatism) response; Proportion of patients with ACR20/50/70 response; Proportion of patients with a remission according to DAS28/SDAI/CDAI ; Health Assessment Questionnaire (HAQ) score and pain assessment ; Van Der Heijde Modified Total Sharp Score [X-ray score] ; EuroQol 5-D score, Health Utility Index, Cost Diary, In/Outpatient cost, Work Productivity and Activity Impairment (WPAI) Questionnaire ; Safety will be evaluated in terms of: maximum toxicity grade experienced by each patient, for each toxicity, according to NCI-CTCAE version 4.03; patients experiencing grade 3-4 toxicity for each specific toxicity; type, frequency and nature of SAEs; patients with at least a SAE; patients with at least a SADR; patients with at least a SUSAR.; Compliance will be evaluated in terms of: number of administered cycles; reasons for discontinuation and treatment modification; dose intensity.; Relation with other people and enjoyment of life questionnaire (2 item Brief Pain Inventory);Timepoint(s) of evaluation of this end point: 12 and 24 weeks; 12 and 24 weeks; 24, 48 and 96 weeks; 24, 48 and 96 weeks; 48 and 96 weeks; 48 and 96 weeks; During the study; At the end of the study; 12, 24, 48, 60, 72, 96 weeks | — |
Countries
Italy
Contacts
Public ContactLab Metodologia per la Ricerca Clin
IRCCS Istituto di Ricerche Farmacologiche Mario Negri
Outcome results
None listed