Prospective controlled study of reduced-dose Rituximab in rheumatoid

INTERVENTION: Trade Name: MabThera Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: RITUXIMAB CAS Number: 174722‐31‐7 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1000‐ CONDITION: rheumatoid arthritis Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05] PRIMARY OUTCOME: Main Objective: To investigate whether a reduced‐dose dosing regimen (1x500mg semiannually) of rituximab (RTX) (Mabthera®) is non‐inferior in patients with rheumatoid arthritis (RA) whose disease is in persistent low disease activity (LDA) or clinical remission (REM) (pLDA/pREM) as compared to the standard dosing regimen of 1x1000mg semi‐annual infusions. Primary end point(s): Primary end points will be the proportions of flares in both groups evaluated by the disease activity score 28 (DAS28). Disease flare will be defined as a change in DAS28 of >1.2 or an increase in DAS28 of 0.6‐1.2 if this results in DAS28 >3.2 ("reverse" EULAR improvement criteria). DAS28 is defined as follows: 0.56 * sqrt(TJC) + 0.28 *sqrt(SJC) + 0.70*ln(ESR) + 0.014*GH. ESR=erythrocyte sedimentation rate. Secondary Objective: not applicable Timepoint(s) of evaluation of this end point: months 3, 6, 9, 12, 15, 18, 21, 24 SECONDARY OUTCOME: Secondary end point(s): Secondary outcome measures will include radiographic progression as measured by change in the Sharp modified van der Heijde (SvdH) score on standard radiographs, as well as physical function, as measured by the health assessment questionnaire disability index (HAQ‐DI). Timepoint(s) of evaluation of this end point: months 12, 24 INCLUSION CRITERIA: • Diagnosis of RA according to the 2010 ACR/EULAR classification criteria • Current treatment with RTX (at time of inclusion have already received at least 2 cycles of 1000mg RTX) at the Day‐Clinic of the Division of Rheumatology of the Medical University of Vienna • Persistent low disease activity or clinical remission. Persistent clinical remission (pREM) will be defined as a simplified disease activity index (CDAI) =2.8 measured at two time‐points 6 months apart. The CDAI is calculated as follows: TJC + SJC + GH + EGH (EGH=evaluator's assessment of general health on a 100 mm VAS, GH=patient's assessment of general health on a 100 mm VAS, SJC=28 swollen joint count, TJC=28 tender joint count). • Persistent low disease activity (pLDA) will be defined as a CDAI =10 measured at two timepoints 6 months apart • Patients who achieve REM at only either one of the two successive time‐points will be considered as having pLDA with regard to the current tr