日本的研究人员近期指出，那些对口服激素治疗疗效较差的青少年特发性关节炎（JIA）患儿对隔周8mg/kg的tocilizumab治疗应答良好，开始治疗后不久就可以观察到患者发热的消退及重要实验室检查指标的改善，治疗18周的不良反应发生率较低。

共有56名JIA患者入组，均对口服激素治疗应答不良。平均年龄为8.3岁，JIA平均病程为4.5年，激素用量平均为0.51mg/kg/d。最初6周为单盲、开放性研究阶段，在给予tocilizumab治疗后发现，症状改善达30%、50%和70%的患者分别占91.1%、85.7%和67.9%。大部分患者的高热症状在用药后立即得到控制。白细胞增多、血小板增多、贫血、C反应蛋白的升高及血沉等情况均于用药后得到明显改善。43名达到应答标准的患者随后自愿进入双盲研究阶段，随机进入tocilizumab治疗组（n=20）和安慰剂组（n=23）。在该阶段，两组中各有1人因为不良反应而中途退出研究，未发现新发结核病例。
      
           
研究人员指出，tocilizumab在治疗JIA方面具有光明的前景，目前仅日本批准了tocilizumab的上市，且卡斯尔曼氏病是唯一的治疗指征。

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RoActemra launched for rheumatoid arthritis

Roche has launched RoActemra (tocilizumab) for use in combination with methotrexate (MTX) to treat moderate to severe active rheumatoid arthritis in adults with an inadequate response or intolerance to one or more DMARDs or TNF antagonists, or as monotherapy in these patients in case of MTX intolerance or where continued treatment with MTX is inappropriate.

PHARMACOLOGY

Tocilizumab is a humanised IgG1 monoclonal antibody that prevents interleukin-6 [IL-6] from binding to the IL-6 receptor.¹ It is the first licensed biological agent to inhibit IL-6, a major cytokine in the inflammatory network.

CLINICAL STUDIES

In a randomised double-blind trial involving 622 patients with moderate to severe active rheumatoid arthritis with an inadequate response to MTX, significantly more patients receiving tocilizumab 8mg/kg (n=205) or 4mg/kg† (n=213) (given every four weeks with weekly MTX) had an ACR20* response by week 24 than those receiving placebo (n=204) (59 per cent and 48 per cent, respectively vs 26 per cent).²

In the same trial the disease activity score using 28 joint counts (DAS28) decreased rapidly in the tocilizumab groups with DAS28 remission (<2.6) at week 24 achieved in significantly more patients in the tocilizumab 8mg/kg and 4mg/kg^† groups than in the placebo group (27 per cent and 13 per cent vs 0.8 per cent).²

Similar results were observed in another trial involving 499 patients with moderate to severe active rheumatoid arthritis and failure to respond, or intolerance to one or more TNF antagonists within the previous year.³ In this trial significantly more patients receiving tocilizumab 8mg/kg or 4mg/kg^† (in combination with MTX) achieved an ACR20 response by week 24 compared with those receiving placebo (50.0 per cent and 30.4 per cent vs 10.1 per cent) and significantly more achieved DAS28 remission at week 24 (30.1 per cent and 7.6 per cent vs 1.6 per cent).

The proportion of patients who achieved an ACR70 response was significantly increased in the tocilizumab 8mg/kg groups in both studies.^2,3

Tocilizumab has also been shown to produce significant improvements in fatigue (FACIT-fatigue) and quality of life (SF-36 physical and mental) scores at both doses† compared with placebo.²

In the trials most adverse events were mild to moderate occurring with a similar overall incidence in all groups.³ The incidence of serious adverse events was comparable across all groups.^2,3

REFERENCES

1. RoActemra Summary of Product Characteristics, 2009.
2. Smolen JS et al. Lancet 2008; 371:987-97.
3. Emery P et al. Ann Rheum Dis 2008; 67:1516-23.

4mg/kg is not a licensed or recommended starting dose.

ACR20 or 70=20% or 70% improvement in rheumatoid arthritis signs and symptoms according to American College of Rheumatology (ACR) criteria.