title: Pharmacokinetics and pharmacodynamics of tocilizumab after subcutaneous administration in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate the pharmacokinetics, pharmacodynamics, safety and efficacy of subcutaneous tocilizumab 162 mg weekly (QW) or every other week (Q2W) in rheumatoid arthritis patients on methotrexate.
  
  
  METHODS
  This was a multicenter, open-label, randomized, parallel group study. Patients were randomly assigned to receive tocilizumab 162 mg subcutaneously QW or Q2W for 12 weeks. Pharmacokinetic and pharmacodynamic measurements were taken from baseline through to treatment end. Efficacy was assessed at baseline and Q4W thereafter. Safety and tolerability were monitored.
  
  
  RESULTS
  29 patients received tocilizumab treatment for 12 weeks. After final QW and Q2W dosing, mean ± SD for Cmax, Cmin and AUC0-168h/0-336h was 39.4 ± 18.1 and 10.7 ± 6.6 μg/ml, 27.9 ± 14.7 and 2.3 ± 3.2 μg/ml and 5,505 ± 2,632 and 2,332 ± 1,696 μg×h/ml. Median tmax was 2 - 3 days. Mean soluble interleukin-6 receptor (sIL-6R) complex concentration increased within 1 week and plateaued (670 ± 211 (QW); 387 ± 194 ng/ml (Q2W)) by final dosing; median C-reactive protein (CRP) levels decreased to below upper limit of normal after first and third doses; mean ± SD (range) reduction in Disease Activity Score using 28 joints at Week 12 was similar between groups (-2.5 ± 1.2 (-4 to -1); -3.1 ± 1.1 (-5 to -2)). Patients experiencing ≥ 1 adverse event were comparable between groups (71% vs. 80%).
  
  
  CONCLUSIONS
  Greater tocilizumab exposure and sIL-6R elevation and more rapid CRP level normalization occurred with QW than with Q2W dosing. Both regimens demonstrated clinical benefit and were well tolerated.
authors.affiliation: Hoffmann-La Roche Inc., Nutley, NJ, USA. zhangxiaoping@aol.com
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Ya-Chi
authors.initials: YC
authors.lastname: Chen
authors.forename: Scott
authors.initials: S
authors.lastname: Fettner
authors.forename: Lucy
authors.initials: L
authors.lastname: Rowell
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gott
authors.forename: Paul
authors.initials: P
authors.lastname: Grimsey
authors.forename: Adam
authors.initials: A
authors.lastname: Unsworth
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D002097:C-Reactive Protein; C502936:tocilizumab