GP2013 in the Treatment of RA Patients Refractory to or Intolerant of Standard Therapy

Maximum serum concentration (Cmax) after the first infusion of GP2013, MabThera and Rituxan in patients with RA. Samples collected from baseline up to 24 weeks: Day 1, 4, 8, 15, 18, 29, 57, 85,113 and 169.

Area under the effect curve of percent change of peripheral B-cell count from baseline to Day 14 (AUEC(0-14d)) of GP2013, MabThera and Rituxan in patients with RA

Change from baseline in Disease Activity Score 28 joint count - C-reactive proteine DAS28(CRP) at Week 24.

In order to calculate the DAS28(CRP) the number of tender joints and swollen joints were assessed using 28-joint count (tender28 and swollen28).The patient's global assessment of disease activity (GH) measured on a Visual Analogue Scale (VAS from 0mm - best to 100mm - worst) was obtained.

DAS28(CRP) = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * GH + 0.96 The DAS28(CRP) provides a number on a scale from 0 to 10 indicating the current activity of the RA, while lower values correspond with less disease activity. A decrease in DAS28 signifies a clinical improvement.

A patient will be considered as improved according the ACR20 criteria

• at least 20 % improvement from baseline in tender joint count, using the 68-joint count
• at least 20 % improvement from baseline in swollen joint count, using the 66-joint count
• and at least 20% improvement from baseline in a least 3 of the following 5 measures:
• Patient's assessment of RA pain (VAS 100 mm)
• Patient's global assessment of disease activity (VAS 100 mm)
• Physician's global assessment of disease activity (VAS 100 mm)
• Patient self-assessed disability (Health Assessment Questionnaire disability index)
• Acute phase reactant (C-reactive protein or erythrocyte sedimentation rate)

In order to calculate the Clinical Disease Activity Index (CDAI) the number of tender and swollen joints were assessed using the 28 -joint count (tender28 and swollen28). The patient's global assessment of disease activity and the physician's global assessment of disease activity were measured using a Visual Analogue Scale (VAS) of 10 cm (from 0=best to 10=worst).

CDAI = tender28 + swollen28 + patient's global assessment (in cm) + physician's global assessment (in cm)

In order to calculate the Simplified Disease Activity Index (SDAI) the number of tender and swollen joints were assessed using the 28 -joint count (tender28 and swollen28). The patient's global assessment of disease activity and the physician's global assessment of disease activity were measured using a Visual Analogue Scale (VAS) of 10 cm (from 0=best to 10=worst).

SDAI = CDAI + CRP (in mg/dL)

(CDAI = tender28 + swollen28 + patient's global assessment (in cm) + physician's global assessment (in cm))

Present DAS28 ≤ 3.2 (low): good response (if improvement > 1.2), moderate response (if improvement >0.6 and ≤ 1.2), no response (if improvement ≤ 0.6).

Present DAS28 > 3.2 to ≤ 5.1 (moderate): moderate response (if improvement > 1.2), moderate response (if improvement >0.6 and ≤ 1.2), no response (if improvement ≤ 0.6).

Present DAS28 > 5.1 (high): moderate response (if improvement > 1.2), no response (if improvement >0.6 and ≤ 1.2), no response (if improvement ≤ 0.6).