Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis

Abstract

ObjectiveTo evaluate the efficacy and safety of switching from intravenous (IV) tocilizumab (TCZ) to subcutaneous (SC) TCZ monotherapy in rheumatoid arthritis patients.MethodsPatients who had completed 24 weeks of TCZ‐SC (162 mg/2 weeks) or TCZ‐IV (8 mg/kg/4 weeks) monotherapy in the double‐blind period of the MUSASHI study were enrolled in an 84‐week open‐label extension period. All received TCZ‐SC (162 mg/2 weeks) monotherapy. Effects of the IV to SC switch were evaluated at week 36 (12 weeks after switching).ResultsOverall, 319 patients received ≥1 dose of TCZ‐SC during the open‐label extension period; 160 switched from TCZ‐IV to TCZ‐SC (TCZ IV/SC) and 159 continued TCZ‐SC (TCZ SC/SC). Disease Activity Score in 28 joints using the erythrocyte sedimentation rate clinical remission rates were 62.5% (100 of 160) for TCZ IV/SC and 50.0% (79 of 158) for TCZ SC/SC at week 24, and were maintained at 62.5% (100 of 160) and 57.0% (90 of 158), respectively, at week 36. In the TCZ IV/SC group, 9% of patients (9 of 100) who had achieved remission at week 24 could not maintain remission at week 36. In TCZ IV/SC patients weighing ≥70 kg, the percentage with a sufficient serum TCZ concentration (≥1 μg/ml) decreased from 90.9% (10 of 11) at week 24 to 45.5% (5 of 11) at week 36. Overall safety profiles were similar in TCZ IV/SC and TCZ SC/SC except for mild injection site reactions in TCZ IV/SC.ConclusionEfficacy is adequately maintained in most patients switching from TCZ‐IV (8 mg/kg/4 weeks) to TCZ‐SC (162 mg/2 weeks) monotherapy. Patients receiving TCZ‐IV can switch to TCZ‐SC without serious safety concerns. Clinical efficacy may be reduced after switching in some patients with high body weight.

Safety and effectiveness of subcutaneous tocilizumab in patients with rheumatoid arthritis in a real-world clinical setting

“…Similar results were observed in the 84-week open-label extension period of the phase III MUSASHI study, as well as in a real-world comparison of DAS28-ESR clinical response in patients at baseline and 3 months after switching from TCZ-IV to TCZ-SC [18,19]. TCZ-SC potentially reduced disease activity in TCZ-naïve patients.…”

“…In the phase III SUMMACTA study, the efficacy and safety profiles in patients who switched from TCZ-IV in combination with csDMARDs to TCZ-SC were comparable with those in patients who maintained TCZ-IV [13,17]. Similar results were observed with TCZ monotherapy in the phase III MUSASHI study, in which patients who received TCZ-IV monotherapy and switched to TCZ-SC monotherapy experienced efficacy and safety comparable with those in patients who received TCZ-IV monotherapy [18]. However, data from these clinical trials may not fully represent the safety and effectiveness of TCZ-SC in patients in real-world clinical settings.…”

“…TCZ-SC was given at a fixed dose, and patients with a higher BMI may fail to maintain serum trough concentrations of TCZ required for a response. Previous studies showed that following a switch from TCZ-IV every 4 weeks to TCZ-SC every 2 weeks, patients with higher body weight had reduced TCZ serum trough concentrations and reduced efficacy [18,26].…”

A randomized, double-blind, parallel-group, phase III study of shortening the dosing interval of subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis and an inadequate response to subcutaneous tocilizumab every other week: Results of the 12-week double-blind period

“…A subanalysis of patients in the 84-week open-label period of the MUSASHI trial who switched from TCZ-IV q4w to TCZ-SC q2w showed that efficacy was maintained; however, the response rate for remission was decreased in patients with high body weight (!70 kg), which correlated with lower TCZ serum trough levels [11]. During the MUSASHI open-label period, patients with an inadequate response to TCZ-SC q2w could have their dosing interval shortened and receive TCZ-SC qw, which resulted in increased TCZ serum trough levels and improved efficacy with a comparable safety profile [12].…”

Subcutaneous Tocilizumab May Be Less Effective than Intravenous Tocilizumab in the Treatment of Juvenile Idiopathic Arthritis–associated Uveitis

“…Several clinical trials have shown the safety and efficacy profile of TCZ-SC to be comparable to that of TCZ-IV 7 . Switching from TCZ-IV to SC was shown to be generally successful and sustained over time 8 . A recent study analyzed clinical data from 58 patients with RA who switched from TCZ-IV to TCZ-SC, suggesting that the switch in realworld settings is effective and can be considered for convenience 9 .…”