RA patients with active RA despite treatment with DMARDs. MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: RoActemra
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: TOCILIZUMAB
CAS Number: 375823-41-9
Other descriptive name: TOCILIZUMAB
Concentrat
Sponsors
University Medical Center Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • • Able and willing to give written informed consent. • Have sufficient knowledge of the Dutch language to be able to comply with the requirements of the study protocol. • At least 18 years of age. • Diagnosed as having RA and meeting the 2010 ACR/EULAR criteria for RA (Appendix A). • Active RA defined by CDAI>10 and at least 1 swollen joint of the 28 joint count. • For patients =65 years) no F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Having a contraindication for treatment with systemic GCs (as determined by the treating rheumatologist, in line with regular care). • Having a contraindication for treatment with TCZ, as determined by the treating rheumatologist or as described in the Summary of Product Characteristics (SPC) Paragraph 4.3, page 33. ‘Special warnings and precautions for use’ as described in the SPC Paragraph 4.4, page 33, should be strictly followed. • Use of systemic GCs (including i.a. GCs) within 4 weeks before the screening visit. • Current use of a bDMARD or tsDMARD; i.e. these need to be discontinued before start of study medication. Wash out periods for bDMARDs and tsDMARDs should follow routine care. • Treatment with any investigational agent within 4 weeks prior to the screening visit. • Having any other inflammatory rheumatic disease than RA., except for secondary Sjögren’s syndrome will be allowed, as well as RA-overlap syndromes that are primarily treated as RA at the time of screening. • Female who is pregnant (by anamnesis) or breast feeding, or considering becoming pregnant during the study period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether adding TCZ (subcutaneously 162 mg/week) to current csDMARD therapy is more effective in reducing disease activity than adding prednisone (orally 10 mg/day) in a usual care treat-to-target strategy in patients with insufficient response to DMARD therapy (DMARD-IR).;Secondary Objective: Secondary Efficacy Objective(s): -To compare treatment strategies on drug retention (TCZ vs prednisone), as surrogate measure of drug efficacy and tolerability, and on drug treatment over time. -To assess whether TCZ is more effective than prednisone in reaching different criteria for response, clinical remission, and low disease activity; and on reduction of radiographic progression. -To compare treatments on costs and effects in a cost-effectiveness analysis Secondary Patient-Reported Outcome Objectives: -To assess whether TCZ is more effective than prednisone with regard to quality of life, functional ability, fatigue, sleep quality, and anxiety and depression. -To compare treatments on costs and quality of life (utility) in a cost-utility analysis Secondary Safety Objectives: -To assess the occurrence of serious adverse events (SAEs), glucocorticoid-associated AEs and TCZ-associated AEs ;Primary end point(s): Change in CDAI from baseline to 6, 9, and 12 months;Timepoint(s) of evaluation of this end point: Baseline to 6, 9, and 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SECONDARY EFFICACY ENDPOINTS: - Change in CDAI from baseline to 6 months - Change in SDAI and change in DAS28 from baseline to 12 months. - Drug retention rate, defined as the proportion of patients at 12 months on the treatment (TCZ/prednisone) to which they were allocated. - Switch rate, defined as the proportion of patients who switched during the study period to treatment of the other arm. - Average dose of TCZ or prednisone from baseline up to 12 months. - ACR20, ACR50, and ACR70 response (using 28 joint counts), EULAR good or moderate response. - Proportion of patients reaching a state of clinical remission at any time during the study defined by different criteria: CDAI=2.8 AND max 1 swollen joint of the 28 joint count, CDAI=2.8, SDAI=3, DAS28<2.6, and ACR-EULAR Boolean remission (defined by a tender joint count =1, a swollen joint count =1, a C-reactive protein =1mg/dL, and a patient global assessment =1 on a 0-10 scale). - Time to reach a state of clinical remission defined by the criteria mentioned before. - Proportion of patients reaching at least a state of low disease activity (defined by 2.8<CDAI=10, 3.3<SDAI=11, 2.6=DAS28<3.2,) during the study. - Change in Sharp/van der Heijde (SvH) score from baseline to 12 months - Change in quality of life from baseline to 12 months (using the EQ5D) - Change in functional ability from baseline to 12 months (using the Dutch consensus HAQ) - Change in fatigue (using the FACIT-F), sleep quality (using the PSQI) and anxiety and depression (using the HADS) from baseline to 12 months. - Direct medical (e.g. GP visits) and non-medical (e.g. travel expenses) costs as well as indirect costs (e.g. productivity loss) using the Health Care Utilisation and Work Productivity Questionnaire, and observed drug use and visits to the rheumatology clinic. - Quality Adjusted Life Years (based on EQ5-D utility scores over time). SECONDARY SAFETY ENDPOINTS: - GC Toxicity Index (GTI) score at 6, 9 and 12 months - | — |
Countries
Netherlands
Contacts
Public ContactRheumatology & Clinical Immunology
University Medical Center Utrecht
Outcome results
None listed