The purpose of this study is to find biological response patterns of patients with rheumatoid arthritis to drugs with different biologic modes of action. This study should help to predict therapeutic responses and to find the right therapy for the right patient.
The investigators propose a randomised, multi-centre strategic biomarker trial of rheumatoid arthritis (RA) patients with failure to methotrexate or leflunomide to one of the four current biological modes of action: targeting TNF (infliximab); co-stimulation (abatacept); IL-6R (tocilizumab); and B cells (rituximab); all agents are licensed for RA and have evidence for efficacy in this indication. Predictors of response to therapy after 24 weeks will be analysed, and include baseline and follow up assessments of clinical, functional, structural, laboratory tests (routine, autoantibodies, cytokines, gene expression, and susceptibility genes). In a second phase, patients not achieving LDA/REM will be randomised to one of the remaining MoA. Two hundred patients, who are started on a new biological therapy will be enrolled over an estimated period of 5 years; 50 patients per group will be included, and studied for a period of 12 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
115
\- Infliximab (Remicade®) will be administered i.v. at a dose of 3 mg/kg at 0 and 2 weeks, and 5 mg/kg at weeks 6, 14, and 22, 30, 38, and 46.
\- Abatacept (Orencia®) will be given i.v. at weeks 0, 2, 4, and then every 4 weeks until week 48 at a weight adjusted dose: \<60 kg Body weight (BW): 500 mg; \>60-100 kg BW: 750 mg; alternatively, based on preference and shared decision between patient and physician, patients randomized to the abatacept arm may receive s.c. application at a dose of 125mg weekly.
\- Tocilizumab (Ro-Actemra®) will be administered every 4 weeks at a dose of 8 mg/kg BW (maximum dose of 800 mg); The employed dosage will be calculated using manufacturer guidelines; alternatively, based on preference and shared decision between patient and physician, patients randomized to the tocilizumab arm may receive s.c. application at a dose of 162mg every week.
Gesundheitszentrum Mariahilf
Vienna, Austria
AKH Wien
Vienna, Austria
Krankenhaus Hietzing
Vienna, Austria
Hanusch Krankenhaus
Vienna, Austria
Absolute Change in the Simplified Disease Activity Index (SDAI)
Time frame: 24 Weeks
Relative Change in the SDAI in percent
Time frame: 24 Weeks
Absolute and relative change in the Clinical Disease Activity Index (CDAI) in percent
Time frame: 24 Weeks
Absolute and relative change in the Disease Activity Score 28 (DAS28) in percent
Time frame: 24 weeks
Achieving an SDAI or CDAI response (50%, 70%, 85%)
Time frame: 24 Weeks
Achieving a EULAR response (European League Against Rheumatism)
Time frame: 24 Weeks
Achieving an ACR response (20%, 50%, 70%) (American College of Rheumatology)
Time frame: 24 Weeks
Change in quality of life (EuroQoL-5D, SF-36)
Time frame: 24 weeks
Change in fatigue (Fatigue Score on the Visual Analog Scale)
Time frame: 24 Weeks
Proportion achieving a low disease activity state (SDAI ≤11)
Time frame: 24 Weeks
Proportion achieving a remission state (SDAI ≤3.3)
Time frame: 24 Weeks
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\- Rituximab (Mabthera®) will be given as 1000mg at weeks 0 and 2, and then repeated at weeks 24 and 26. Patients will receive 100 mg methylprednisolon i.v. before each infusion, as well as 1000mg paracetamol, as well as 50mg diphenhydramine hydrochloride (Dibondrin©).
Wilhelminenspital
Vienna, Austria
Ordination Wels (Private Medical Office)
Wels, Austria
Institute of Rheumatology
Prague, Czechia
V. A. Nasonova Research Institute of Rheumatology
Moscow, Russia
Kantonsspital St.Gallen, Klinik für Rheumatologie
Sankt Gallen, Switzerland
Radiographic progression - (Van der Heijde/Sharp Score)
Time frame: 6 months and 12 months
Change in physical function (HAQ)
Time frame: 24 Weeks
Change in sleep (Sleep Score on the Visual Analog Scale)
Time frame: 24 Weeks