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

Abstract

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, Modern Rheumatology, 28:1, 76-84, DOI: 10.1080/14397595.2017 Methods: Adult patients in Japan with inadequate response to TCZ-SC q2w were randomized to either TCZ-SC 162 mg qw monotherapy or TCZ-SC 162 mg q2w monotherapy for 12 weeks (double-blind). The primary endpoint was the change from baseline in adjusted Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) at week 12. Efficacy, safety and pharmacokinetics were assessed.Results: TCZ-SC qw was superior to TCZ-SC q2w for adjusted mean change in DAS28-ESR from baseline to week 12. The difference in the change in DAS28-ESR between TCZ-SC qw and q2w was À1.21 (95%CI: À2.13, À0.30, p ¼ .0108). A higher proportion of patients receiving TCZ-SC qw achieved DAS28-ESR remission/low disease activity than TCZ-SC q2w. Adverse events were 71.4% and 66.7% for TCZ-SC qw and q2w, respectively; infection was the most common event with one fatal case with TCZ-SC qw.Conclusions: In patients with inadequate response to TCZ-SC q2w, shortening the dosing interval to qw improved efficacy with acceptable tolerability. Occurrence of infection for both TCZ q2w and qw is important and needs careful attention.ARTICLE HISTORY

Efficacy of Monotherapy with Biologics and JAK Inhibitors for the Treatment of Rheumatoid Arthritis: A Systematic Review

“…Another study in Japanese patients, focusing on patients with an inadequate response to q2w dosing, compared two different sc TCZ dosing frequencies. Change in DAS28(ESR) was significantly greater over 12 weeks with qw dosing than with q2w dosing [ 69 ].…”

Long-term safety and efficacy of weekly subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis who had an inadequate response to subcutaneous tocilizumab every other week: Results from the open-label extension of the SHINOBI study

“…The eligibility criteria for participation have been described [15]. Briefly, patients !20 years of age with RA for !6 months (1987 American College of Rheumatology [ACR] criteria) who had received TCZ-SC !4 times with the q2w regimen prior to enrollment and had an inadequate response were included.…”

“…All endpoints and analysis methods were pre-specified in the protocol and/or the statistical analysis plan. Since the superiority was reported previously [15], statistical comparisons were not performed in this report in accordance with the American Statistical Association's statement on p values [18].…”

“…Baseline demographics, clinical characteristics, and history of treatment at baseline have been described previously [15].…”

“…To confirm the efficacy and safety of TCZ-SC qw monotherapy, a randomized, double-blind, parallel-group, 12-week phase III study (SHINOBI) was conducted to compare the safety and efficacy of TCZ-SC qw monotherapy with that of TCZ-SC q2w monotherapy in Japanese patients with RA who had an inadequate response to TCZ-SC q2w [15]. The study met its primary endpoint by demonstrating the superiority of TCZ-SC qw to TCZ-SC q2w for adjusted mean change in Disease Activity Score based on 28 joints using erythrocyte sedimentation rate (DAS28-ESR) from baseline to week 12; the adjusted difference in the change in DAS28-ESR between the TCZ-SC qw and TCZ-SC q2w groups was À1.21 (95% CI, À2.13 to À0.30; p ¼ .0108).…”