Relationships between free tocilizumab, sIL-6R, percentage of sIL-6R bound to tocilizumab, and CRP in serum. (A) Relationship between serum free tocilizumab (●), serum sIL-6R (○), and the percentage of sIL-6R bound to tocilizumab in an immune complex (IC). Serum sIL-6R (○) includes all sIL-6R: free, bound to tocilizumab, and bound to IL-6. Increased sIL-6R after tocilizumab infusion formed an immune complex with tocilizumab. Almost all sIL-6R was bound to tocilizumab while serum-free tocilizumab was detectable (1 μg/mL or more). This figure shows a representative data from the phase 1 study in healthy individuals. (B) Relationship between serum tocilizumab and percentage of sIL-6R bound to tocilizumab (phase 1/2 study in RA). More than 95% of sIL-6R was bound to tocilizumab while serum-free tocilizumab remained 1 μg/mL or more. (C) Relationship between serum tocilizumab and CRP. Serum CRP was normalized as long as the free tocilizumab concentration remained 1 μg/mL or more (phase 1/2 study in RA). The sensitivity of CRP assay in the present study was 0.03 mg/dL, and the normal range was less than 0.2 mg/dL.