Background/Purpose: Tocilizumab (TCZ) blocks interleukin-6-receptor signaling and is an effective rheumatoid arthritis (RA) therapy. The MUSASHI¹ and SUMMACTA² studies showed the efficacy and safety of TCZ 162 mg subcutaneous injection (TCZ-SC) to be comparable to those of TCZ 8 mg/kg intravenous infusion (TCZ-IV). Here we assess the long-term (108-wk) safety and efficacy of TCZ-SC monotherapy in Japanese RA patients (pts).

Methods: This long-term, open-label study followed a 24-wk double-blind, non-inferiority study (MUSASHI study). Pts completing the MUSASHI study were administered 162 mg TCZ-SC every 2nd wk for 84 wks without concomitant DMARDs. Depending on disease activity of individual pts, adjustment of administration interval within a 1- to 3-wk range was allowed after Wk 36.

Results: 346 pts received TCZ for a total exposure of 639.0 pt-yrs. At last observation (Wk 108), 278 pts remained. Most withdrawals were due to AEs (10.3%, 36/346) and insufficient therapeutic response (4.9%, 17/346). AEs occurred at 498.3 events/100 pt-yrs (E/100PY); most common were infections and infestations (138.3 E/100PY). SAEs occurred at 16.9 E/100PY; most common were infections and infestations (5.3 E/100PY). There was 1 death from gastric cancer and disseminated intravascular coagulation. Incidence of malignancy was 0.8 E/100PY. There were no serious anaphylactic events during the TCZ-SC dosing period. The incidence rate of injection site reaction was 13.2% (44/333) in patients who were administered TCZ-SC. The severity of all injection site reactions was mild and tolerable.

  ACR20, 50, and 70 response rates increased slightly with continuous TCZ-SC treatment. At Wk 24, ACR20, 50, and 70 response rates were 84.8% (274/323), 65.9% (213/323), and 39.9% (129/323); and at Wk 108, they were 92.5% (258/279), 80.6% (225/279), and 61.6% (172/279). DAS28 and CDAI remission rates at Wk 48 were 64.7% (202/312) and 27.6% (86/312); at Wk 108 they were 79.6% (222/279) and 47.7% (133/279). TCZ administration interval was shortened in 24 pts due to insufficient response; in those pts, DAS28(SD) improved from 4.63(1.56) at before shortening to 2.39(1.14) at 12 wks after shortening. Administration interval was extended in 26 pts due to sufficient response; in 61.5% of those pts, disease activity remained low during the study period with the interval extended.

Conclusion: The incidence rates of SAEs, serious infections, malignancies, and deaths with TCZ-SC were comparable to those of TCZ-IV pooled data³ in Japanese RA pts, suggesting that the long-term safety profile of TCZ-SC is not different from established TCZ-IV. Efficacy remained stable with long-term exposure to TCZ-SC. TCZ-SC is a tolerable and useful treatment option for RA.

Table Events per 100 pt-yrs in TCZ-SC and TCZ-IV³

1. A Ogata et al. Ann Rheum Dis 2012; 71 suppl 3: 373.

2. G.R.Burmester et al. Arthritis Rheum 2012; 64 suppl 10: S1075

3. Nishimoto et al. Mod Rheumatol 2010; 20:222-32