Background Two global Phase III studies evaluated the safety and efficacy of subcutaneous tocilizumab (TCZ-SC). SUMMACTA was a 97-week study that compared TCZ-SC 162 mg every week (qw) with intravenous TCZ (TCZ-IV) 8 mg/kg every 4 weeks. At week 24, patients (pts) were re-randomized to remain on the initially assigned formulation or switch to the other formulation. BREVACTA was a 96-week study that compared TCZ-SC 162 mg every 2 weeks (q2w) with placebo. From week 12 onward, pts could escape to TCZ-SC qw if they had <20% improvement in both swollen joint count (SJC) and tender joint count (TJC). At week 24, pts were re-randomized to receive TCZ-SC q2w via 2 different devices.
Objectives To assess long-term safety and efficacy of TCZ-SC in US pts who completed the SUMMACTA or BREVACTA core studies.
Methods In this open-label, single-arm, US-based, Phase IIIb study, pts who completed SUMMACTA and BREVACTA could enroll and continue to receive their dosage of TCZ-SC q2w or qw, or switch from TCZ-IV to TCZ-SC qw. Nonbiologic disease-modifying antirheumatic drugs in combination with TCZ-SC were permitted. The primary safety endpoint was the proportion of pts with serious adverse events (SAEs). Secondary endpoints included the proportions of pts with adverse events of special interest and pts who discontinued, incidence of laboratory abnormalities and efficacy assessments.
Results Of 217 pts treated, 76.5% were female and mean age was 58.4 years. A total of 23 pts (10.6%) had ≥1 SAEs, for a rate of 14.7/100 pt-years (Table). The most common SAEs were infections (n=7, 3.2%). Eight pts had ≥1 serious or opportunistic infections or infections requiring IV anti-infectives. Thirty-four pts withdrew from TCZ-SC treatment, 13 (6.0%) due to AEs, 21 (9.7%) due to nonsafety reasons. Aminotransferase elevations were reported in 27.2% of pts but were not associated with liver toxicity. Neutropenia (5.1%) was transient. Injection site reactions occurred in 6 patients, were nonserious and resolved without sequelae. No anaphylaxis or deaths were reported. Mean Clinical Disease Activity Index and 28-joint Disease Activity Scores (DAS28) decreased from baseline and remained stable thereafter.
Conclusions The safety of TCZ-SC during the long-term extension period of the SUMMACTA and BREVACTA studies was consistent with the safety profile established during the core studies, with no new safety signals identified. Mean efficacy improvements observed from baseline were stable over time. These results demonstrate the durability of the safety and efficacy responses with long-term exposure to TCZ-SC.
Disclosure of Interest A. Kivitz Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, Janssen, Pfizer, UCB, Consultant for: BMS, Genentech, UCB, Speakers bureau: BMS, E. Olech Grant/research support from: Genentech, Consultant for: Genentech, M. Borofsky: None declared, J. Devenport Employee of: Genentech, J. Pei Employee of: Genentech, T. Wallace Employee of: Genentech, M. Michalska Employee of: Genentech
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