Background Efficacy and safety of intravenous (IV) tocilizumab (TCZ) has been established in rheumatoid arthritis (RA). Subcutaneous (SC) TCZ injection has been developed as an additional important treatment option to enhance user-friendliness for patients and healthcare professionals.
Objectives To compare the efficacy and safety of SC and IV TCZ monotherapy in Japanese RA patients.
Methods Patients with RA who had responded inadequately to any synthetic or biologic DMARDs were randomized to receive SC TCZ 162 mg Q2W (TCZ-SC) or IV TCZ 8 mg/kg Q4W (TCZ-IV) without any DMARDs. The primary endpoint was to assess the non-inferiority of TCZ-SC to TCZ-IV by the ACR20 response rate at Week 24 in per protocol patients.The non-inferiority margin was predefined at 18%.
Results A total of 346 patients received at least 1 dose of TCZ: 159/173 in TCZ-SC and 156/173 in TCZ-IV were eligible for the per protocol analysis. Baseline demographics were comparable between TCZ-SC and TCZ-IV: body weight (kg, mean ± SD), 53.8±8.7 vs. 54.4±10.1; proportion of patients who previously used TNF- α inhibitor, 19.5% vs. 23.1%; and RA duration (years, mean ± SD), 7.3±7.5 vs. 8.0±7.3. At Week 24, 79.2% (95% CI: 72.9, 85.5) of TCZ-SC patients and 88.5% (95% CI: 83.4, 93.5) of TCZ-IV patients had achieved an ACR20 response: the difference (95% CI) was -9.4% (-17.6, -1.2), confirming the non-inferiority of TCZ-SC to TCZ-IV. ACR50 and 70 response rates, change of DAS28 and rates of Boolean remission were also similar between TCZ-SC and TCZ-IV. The serum trough concentrations of TCZ in TCZ-SC and TCZ-IV were similar over time. In both, serum CRP was normalized while serum TCZ concentration remained above 1 μg/mL. Serum TCZ concentrations remained above 1 μg/mL at Week 24 in 85.9% of TCZ-SC patients and in 89.4% of TCZ-IV patients. The incidence of adverse events (AEs) over 24 weeks was 89.0% in TCZ-SC and 90.8% in TCZ-IV. There was no death in this study. Safety profiles were comparable between TCZ-SC and TCZ-IV: serious AEs, 7.5% vs. 5.8%; serious adverse drug reactions, 3.5% vs. 5.8%; serious infections, 1.2% vs. 2.9%; and injection site reactions (ISR), 12.1% vs. 5.2%. All ISRs were mild and manageable. Anti-TCZ antibodies were detected more frequently in MRA-SC than in MRA-IV. No case of serious ISR and anaphylactoid reaction were seen in patients with positive anti-TCZ antibodies.
Conclusions TCZ-SC was non-inferior to TCZ-IV for ACR20 response rates. Other efficacy variables were also comparable between TCZ-SC and TCZ-IV. Serum trough concentration of TCZ in TCZ-SC was comparable to TCZ-IV. The clinical safety profile of TCZ-SC was consistent with that of TCZ-IV, and TCZ-SC was as well-tolerated as TCZ-IV.
Disclosure of Interest A. Ogata Consultant for: Chugai Pharmaceutical CO., LTD
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