西芦库单抗治疗类风湿关节炎疗效与安全性的Meta分析
|
摘要
目的评价西芦库单抗治疗类风湿关节炎(RA)的疗效与安全性。方法电子检索PubMed、Cochrane图书馆、 Embase、 Web of Science、中国知网、中国生物医学文献数据库、维普和万方数据库中关于西芦库单抗治疗RA的随机对照试验(RCT),检索时限为建库至2018年11月。采用RevMan 5.3软件对疗效指标和安全性指标进行Meta分析。结果共纳入5项RCT,合计3 103例RA患者。Meta分析结果显示,西芦库单抗组RA病情缓解20%、 50%、 70%的受试者人数(ACR20、 ACR50、 ACR70)均高于安慰剂组,差异有显著意义(P<0.01);西芦库单抗100 mg q2w组ACR指标显著优于西芦库单抗50 mg q4w组(RR=1.10, 95%CI:1.03～1.17, P=0.005)。安全性方面,西芦库单抗组不良事件发生率、严重不良事件发生率、因不良事件退出率、感染发生率以及注射部位反应发生率均显著高于安慰剂组(P <0.01);西芦库单抗100 mg q2w组注射部位反应发生率高于西芦库单抗50 mg q4w组(RR=1.53, 95%CI:1.07～2.19, P=0.02),两组间其他不良反应发生率相当(P> 0.05)。结论西芦库单抗治疗RA疗效肯定,但应注意治疗过程中发生严重不良事件的风险。
AIM To evaluate the efficacy and safety of sirukumab for patients with rheumatoid arthritis( RA). METHODS The randomized controlled trials( RCTs) of sirukumab in the treatment of RA were searched in PubMed, Cochrane library, Embase, Web of Science, CNKI, China biomedical literature database( CBM), VIP and Wanfang database with a search time limit of building the library until November2018. Meta-analysis of efficacy and safety indicators was performed using RevMan 5.3 software. RESULTS Five RCTs involving 3 103 patients were included. Meta-analysis results showed the America College of Rheumatology20, 50, 70 response( ACR20, ACR50 and ACR70) of the sirukumab group were higher than the placebo group(P < 0.01). The ACR index of the sirukumab 100 mg q2 w group was significantly better than that of the sirukumab 50 mg q4 w group(RR = 1.10, 95%CI: 1.03-1.17, P = 0.005). In terms of safety, the risks of adverse events, serious adverse events, withdrawal from adverse events, infections and injection site reactions in the sirukumab group were higher than the placebo group(P < 0.05). The incidence of injection site reactions in the sirukumab 100 mg q2 w group was higher than that in the sirukumab 50 mg q4 w group(RR = 1.53, 95%CI: 1.07-2.19, P = 0.02). The incidence of other adverse reactions between the two groups was similar(P >0.05). CONCLUSION Sirukumab is effective in the treatment of RA, but the risk of serious adverse events during treatment should be paid attention.
AIM To evaluate the efficacy and safety of sirukumab for patients with rheumatoid arthritis( RA). METHODS The randomized controlled trials( RCTs) of sirukumab in the treatment of RA were searched in PubMed, Cochrane library, Embase, Web of Science, CNKI, China biomedical literature database( CBM), VIP and Wanfang database with a search time limit of building the library until November2018. Meta-analysis of efficacy and safety indicators was performed using RevMan 5.3 software. RESULTS Five RCTs involving 3 103 patients were included. Meta-analysis results showed the America College of Rheumatology20, 50, 70 response( ACR20, ACR50 and ACR70) of the sirukumab group were higher than the placebo group(P < 0.01). The ACR index of the sirukumab 100 mg q2 w group was significantly better than that of the sirukumab 50 mg q4 w group(RR = 1.10, 95%CI: 1.03-1.17, P = 0.005). In terms of safety, the risks of adverse events, serious adverse events, withdrawal from adverse events, infections and injection site reactions in the sirukumab group were higher than the placebo group(P < 0.05). The incidence of injection site reactions in the sirukumab 100 mg q2 w group was higher than that in the sirukumab 50 mg q4 w group(RR = 1.53, 95%CI: 1.07-2.19, P = 0.02). The incidence of other adverse reactions between the two groups was similar(P >0.05). CONCLUSION Sirukumab is effective in the treatment of RA, but the risk of serious adverse events during treatment should be paid attention.
引文
[1]范小冬,向霞,孔文强,等.戈利木单抗治疗类风湿性关节炎的系统评价[J].华西药学杂志, 2018, 33(4):445-449.
[2]汪龙生,吴莉,杨思民,等.以腺苷及其受体信号为靶点的类风湿关节炎疾病和治疗研究进展[J].中国新药与临床杂志,2017, 36(2):70-75.
[3] BOONEN A, MAU W. The economic burden of disease:comparison between rheumatoid arthritis and ankylosing spondylitis[J]. Clin Exp Rheumatol, 2009, 27(4 Suppl 55):S112-S117.
[4] VALLEALA H, KAUPPIM J, KOURI VP, et al. Epstein-Barr virus in peripheral blood is associated with response to rituximab therapy in rheumatoid arthritis patients[J]. Clin Rheumatol, 2015,34(8):1485-1488.
[5] XU Z, BOUMAN TE, COMISAR C, et al. Pharmacokinetics,pharmacodynamics and safety of a human anti-IL-6 monoclonal antibody(sirukumab)in healthy subjects in a first-in-human study[J]. Br J Clin Pharmacol, 2011, 72(2):270-281.
[6] HIGGINS JPT, GREEN S. Cochrane handbook for systematic reviews of interventions version 5.1.0[EB/OL].(2011-03)[2017-11]. http://www.cochrane-handbook.org.
[7] JUNI P, ALTMAN DG, EGGER M. Systematic reviews in health care:assessing the quality of controlled clinical trials[J]. BMJ,2001, 323(7303):42-46.
[8] TAKEUCHI T, THORNE T, KARPOUZAS G, et al. Sirukumab for rheumatoid arthritis:the phaseⅢSIRROUND-D study[J].Ann Rheum Dis, 2017, 76(12):2001-2008.
[9] TAKEUCHI T, YAMANAKA H, HARIGAI M, et al. Sirukumab in rheumatoid arthritis refratory to sulfasalazine or methotrexate:a randomized phase 3 safety and efficacy study in Japanese patients[J]. Arthritis Res Ther, 2018, 20(1):1-11.
[10] ALETAHA D, BINGHAM CO, TANAKA Y, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy(SIRROUND-T):a randomised,double-blind, placebo-controlled, parallel-group, multinational,phase 3 study[J]. Lancet, 2017, 389(10075):1206-1217.
[11] SMOLEN JS, WEINBLATT ME, SHENG S, et al. Sirukumab, a human anti-interleukin-6 monoclonal antibody:a randomised,2-part(proof-of-concept and dose-finding), phaseⅡstudy in patients with active rheumatoid arthritis despite methotrexate therapy[J]. Ann Rheum Dis, 2014, 73(9):1616-1625.
[12] TAYLOR PC, SCHIFF MH, WANG Q, et al. Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic naive patients with active rheumatoid arthritis(SIRROUND-H)a randomised, double-blind, parallel group, multinational, 52-week, phase 3 study[J]. Ann Rheum Dis, 2018, 77(5):658-666.
[13] HOUSSIAU FA, DEVOGELAER JP, VAN DJ, et al. Interleukin-6in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides[J]. Arthritis Rheum, 1988,31(6):784-788.
[14]胡晓敏,宗英,余珊珊,等.类风湿关节炎治疗药物的研发进展及趋势[J].中国新药与临床杂志, 2017, 26(1):36-43.
[15] HODGE DR, HURT EM, FARRAR WL. The role of IL-6 and STAT3 in inflammation and cancer[J]. Eur J Cancer, 2005, 41(16):2502-2512.
[16] BAE SC, LEE YH. Comparison of the efficacy and tolerability of tocilizumab, sarilumab, and sirukumab in patients with active rheumatoid arthritis:a Bayesian network meta-analysis of randomized controlled trials[J]. Clin Rheumatol, 2018, 37(6):1471-1479.
[2]汪龙生,吴莉,杨思民,等.以腺苷及其受体信号为靶点的类风湿关节炎疾病和治疗研究进展[J].中国新药与临床杂志,2017, 36(2):70-75.
[3] BOONEN A, MAU W. The economic burden of disease:comparison between rheumatoid arthritis and ankylosing spondylitis[J]. Clin Exp Rheumatol, 2009, 27(4 Suppl 55):S112-S117.
[4] VALLEALA H, KAUPPIM J, KOURI VP, et al. Epstein-Barr virus in peripheral blood is associated with response to rituximab therapy in rheumatoid arthritis patients[J]. Clin Rheumatol, 2015,34(8):1485-1488.
[5] XU Z, BOUMAN TE, COMISAR C, et al. Pharmacokinetics,pharmacodynamics and safety of a human anti-IL-6 monoclonal antibody(sirukumab)in healthy subjects in a first-in-human study[J]. Br J Clin Pharmacol, 2011, 72(2):270-281.
[6] HIGGINS JPT, GREEN S. Cochrane handbook for systematic reviews of interventions version 5.1.0[EB/OL].(2011-03)[2017-11]. http://www.cochrane-handbook.org.
[7] JUNI P, ALTMAN DG, EGGER M. Systematic reviews in health care:assessing the quality of controlled clinical trials[J]. BMJ,2001, 323(7303):42-46.
[8] TAKEUCHI T, THORNE T, KARPOUZAS G, et al. Sirukumab for rheumatoid arthritis:the phaseⅢSIRROUND-D study[J].Ann Rheum Dis, 2017, 76(12):2001-2008.
[9] TAKEUCHI T, YAMANAKA H, HARIGAI M, et al. Sirukumab in rheumatoid arthritis refratory to sulfasalazine or methotrexate:a randomized phase 3 safety and efficacy study in Japanese patients[J]. Arthritis Res Ther, 2018, 20(1):1-11.
[10] ALETAHA D, BINGHAM CO, TANAKA Y, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy(SIRROUND-T):a randomised,double-blind, placebo-controlled, parallel-group, multinational,phase 3 study[J]. Lancet, 2017, 389(10075):1206-1217.
[11] SMOLEN JS, WEINBLATT ME, SHENG S, et al. Sirukumab, a human anti-interleukin-6 monoclonal antibody:a randomised,2-part(proof-of-concept and dose-finding), phaseⅡstudy in patients with active rheumatoid arthritis despite methotrexate therapy[J]. Ann Rheum Dis, 2014, 73(9):1616-1625.
[12] TAYLOR PC, SCHIFF MH, WANG Q, et al. Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic naive patients with active rheumatoid arthritis(SIRROUND-H)a randomised, double-blind, parallel group, multinational, 52-week, phase 3 study[J]. Ann Rheum Dis, 2018, 77(5):658-666.
[13] HOUSSIAU FA, DEVOGELAER JP, VAN DJ, et al. Interleukin-6in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides[J]. Arthritis Rheum, 1988,31(6):784-788.
[14]胡晓敏,宗英,余珊珊,等.类风湿关节炎治疗药物的研发进展及趋势[J].中国新药与临床杂志, 2017, 26(1):36-43.
[15] HODGE DR, HURT EM, FARRAR WL. The role of IL-6 and STAT3 in inflammation and cancer[J]. Eur J Cancer, 2005, 41(16):2502-2512.
[16] BAE SC, LEE YH. Comparison of the efficacy and tolerability of tocilizumab, sarilumab, and sirukumab in patients with active rheumatoid arthritis:a Bayesian network meta-analysis of randomized controlled trials[J]. Clin Rheumatol, 2018, 37(6):1471-1479.