Background/Purpose: The BREVACTA study assessed the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) in pts with moderate to severe RA who had an inadequate response to ≥ 1 DMARD (21% had failed an antiTNF). The primary objective of the study was to assess efficacy and safety up to week 24; as reported previously, superiority over placebo was demonstrated, with a safety profile comparable to intravenous TCZ (TCZ IV). Here we report the longer-term efficacy and safety data for TCZ SC administration to Week 48.

Methods: This phase 3, randomized, multicenter, parallel-arm study included a 24 week double-blind, PBO controlled period followed by open label treatment for 72 weeks and 8 weeks of safety follow up. Pts were randomized 2:1 to receive TCZ SC 162 mg every 2 weeks (q2w) or PBO SC q2w via a pre-filled syringe (PFS), in combination with stable doses of pre-study DMARD(s). Escape therapy with TCZ SC qw (PFS) was available from week 12. At week 24, pts remaining on q2w therapy in both arms were re-randomized 1:1 to receive open-label TCZ SC q2w via PFS or Autoinjector Pen. The data presented here focuses on pts who received TCZ SC from baseline to week 48, regardless of injection device used.  Efficacy was  assessed  to week 48. Safety was assessed to 29 October 2012 (when all pts had reached ≥ week 48) using AE reports and laboratory data.

Results: 437 pts were randomized at baseline to receive TCZ SC q2w, with 334 (76%) re-randomized at week 24 to continue to receive TCZ SC q2w in the open-label phase. Efficacy was maintained to week 48, with the proportion of pts with ACR20/50/70 responses, in clinical remission (DAS28 < 2.6) and with a clinically meaningful improvement in physical function (change from baseline in HAQ-DI ≥ 0.3) remaining stable or improving from week 24 to 48 (table). Mean reduction in radiographic progression of structural joint damage (measured as change in modified Total Sharp Score, mTSS) was also maintained from week 24 to 48. The rates of AEs and SAEs, including serious infections, remained stable or decreased between weeks 24 and 48. The most common AEs were infections, particularly respiratory ones. No anaphylaxis or medically confirmed serious hypersensitivity occured. The most common injection site reactions were erythema, pain and pruritis. Ten pts developed antiTCZ antibodies postbaseline, but did not experience loss of efficacy or clinically significant or serious hypersensitivity. A total of 21 pts withdrew from TCZ SC due to AEs, most commonly due to infections or elevated liver enzymes. Six pts died up to the week 48 cut-off. 

Conclusion: TCZ SC demonstrated long term efficacy, including sustained ACR response rates and reduced progression of joint damage over 48 weeks. There was no change in the AE profile for TCZ SC compared with earlier evaluations. TCZ SC is an effective treatment in RA, and will offer an alternative route of administration and the possibility of self-administration for pts.