Abstract

Objectives: 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, parallelgroup 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 treatmentend. 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 C_max, C_min and AUC_{0–168h/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 t_max 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.

Author Details

Authors

• Xiaoping Zhang¹
• Ya-Chi Chen¹
• Scott Fettner¹
• Lucy Rowell²
• Tatiana Gott¹
• Paul Grimsey²
• Adam Unsworth²

Departments

• ¹ Hoffmann-La Roche Inc., Nutley, NJ, USA, and
• ² Roche Products Ltd., Welwyn Garden City, UK

Address

Xiaoping Zhang, PhD
Department of Clinical Pharmacology
Hoffmann-La Roche Incorporated
340 Kingsland Street, Nutley, NJ 07110 USA
Email: [email protected]

Citation