期刊论文详细信息
BMC Musculoskeletal Disorders
Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized double-blind controlled studies
Asres Berhan1 
[1] Hawassa University College of Medicine and Health Sciences, P. O. Box: 1560, Hawassa, Ethiopia
关键词: Tofacitinib;    Rheumatoid arthritis;    Meta-analysis;    JAK Inhibitor;    ACR20 response;   
Others  :  1129125
DOI  :  10.1186/1471-2474-14-332
 received in 2013-07-16, accepted in 2013-11-25,  发布年份 2013
PDF
【 摘 要 】

Background

This meta-analysis was conducted to determine the efficacy, safety and tolerability of tofacitinib in the treatment of rheumatoid arthritis in patients with an inadequate response or intolerance to at least one of the nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs).

Methods

Electronic based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), MEDLINE and Cochrane library. The studies included in the meta-analysis were double-blind randomized clinical trials that were conducted in treatment-refractory or intolerant patients with rheumatoid arthritis. The odds ratios (OR), standardized mean differences (SMD) and the 95% confidence intervals (95% CI) were determined by using the random effects model. Heterogeneity among the included studies was evaluated by I2 statistics.

Results

The odds of tofacitinib treated patients who met the criteria for an at least a 20% improvement in the American College of Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated patients (overall OR = 4.15; 95% CI, 3.23 to 5.32). Even though the discontinuation rate due to adverse events was not different from placebo groups, tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to 2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to -0.223) and elevated levels of LDL cholesterol and liver enzymes.

Conclusions

Tofacitinib was effective in the treatment of active rheumatoid arthritis in patients with an inadequate response or intolerance to at least one DMARDs. However, treatment with tofacitinib was associated with infections and laboratory abnormalities.

【 授权许可】

   
2013 Berhan; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150225222304877.pdf 2208KB PDF download
Figure 6. 111KB Image download
Figure 5. 91KB Image download
Figure 4. 83KB Image download
Figure 3. 92KB Image download
Figure 2. 109KB Image download
Figure 1. 28KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】
  • [1]Smolen JS, Aletaha D, Bijlsma JWJ, Breedveld FC, Boumpas D, Burmester G, Combe B, Cutolo M, de Wit M, Dougados M, Emery P, Gibofsky A, Gomez-Reino JJ, Haraoui B, Kalden J, Keystone EC, Kvien TK, McInnes I, Martin-Mola E, Montecucco C, Schoels M, van der Heijde D: Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010, 69:631-637.
  • [2]Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, Paulus HE, Mudano AM, Pisu M, Elkins-Melton M, Outman R, Allison JJ, Almazor MS, Bridges SL, Chatham WW, Hochberg M, Maclean C, Mikuls T, Moreland LW, O’Dell J, Turkiewicz AM, Furst DE: American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008, 59:762-784.
  • [3]Mikuls TR, O’Dell J: The changing face of rheumatoid arthritis therapy: results of serial surveys. Arthritis Rheum 2000, 43(2):464-467.
  • [4]O'Dell JR: Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004, 350:2591-2602.
  • [5]Yazici Y: Treatment of rheumatoid arthritis: we are getting there. Lancet 2009, 374:178-180.
  • [6]Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Genovese MC, Wasko MC, Moreland LW, Weaver AL, Markenson J, Finck BK: A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000, 343(22):1586-1593.
  • [7]Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Mola EM, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M: Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. The Lancet 2004, 363(9410):675-681.
  • [8]LaBranche TP, Jesson MI, Radi ZA, Storer CE, Guzova JA, Bonar SL, Thompson JM, Happa FA, Stewart ZS, Zhan Y, Bollinger CS, Bansal PN, Wellen JW, Wilkie DP, Bailey SA, Symanowicz PT, Hegen M, Head RD, Kishore N, Mbalaviele G, Meyer DM: JAK inhibition with tofacitinib suppresses arthritic joint structural damage through decreased RANKL production. Arthritis Rheum 2012, 64(11):3531-3542.
  • [9]Maeshima K, Yamaoka K, Kubo S, Nakano K, Iwata S, Saito K, Ohishi M, Miyahara H, Tanaka S, Ishii K, Yoshimatsu H, Tanaka Y: The JAK inhibitor tofacitinib regulates synovitis through inhibition of interferon and interleukin17 production by human CD4+ T cells. Arthritis Rheum 2012, 64(6):1790-1798.
  • [10]Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, Gruben D, Wallenstein G, Krishnaswami S, Zwillich SH, Koncz T, Sama K, Bradley J, Mebus C: Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet 2013, 381:451-460.
  • [11]Fleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD, Gruben D, Wallenstein GV, Zwillich SH, Kanik KS: Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 2012, 367(6):495-507.
  • [12]van der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, Cardiel MH, Cohen S, Nash P, Song Y, Tegzova D, Wyman BT, Gruben D, Benda B, Wallenstein G, Krishnaswami S, Zwillich SH, Bradley JD, Connell CA: Tofacitinib (CP690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelvemonth data from a twenty four month phase III randomized radiographic study. Arthritis Rheum 2013, 65(3):559-570.
  • [13]van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, Meijide JAG, Wagner S, Forejtova S, Zwillich SH, Gruben D, Koncz T, Wallenstein GV, Krishnaswami S, Bradley JD, Wilkinson B: Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 2012, 367(6):508-519.
  • [14]Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Jealey LA, Kaplan SR, Liang MH, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31(3):315-324.
  • [15]Sterne JAC, Sutton AJ, Ioannidis JPA, Terrin N, Jones DR, Lau J, Carpenter J, Rücker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duva S, Altman DG, Moher D, Higgins JPT: Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011., 342(d4002) 10.1136/bmj.d4002
  • [16]Fleischmann R, Cutolo M, Genovese MC, Lee EB, Kanik KS, Sadis S, Connell CA, Gruben D, Krishnaswami S, Wallenstein G, Wilkinson BE, Zwillich SH: Phase IIb doseranging study of the oral JAK inhibitor tofacitinib (CP690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to diseasemodifying antirheumatic drugs. Arthritis Rheum 2012, 64(3):617-629.
  • [17]Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, Krishnaswami S, Burgos-Vargas R, Wilkinson B, Zerbini CAF, Zwillich SH: The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum 2009, 60(7):1895-1905.
  • [18]Kremer JM, Cohen S, Wilkinson BE, Connell CA, French JL, Gomez-Reino J, Gruben D, Kanik KS, Krishnaswami S, Pascual-Ramos V, Wallenstein G, Zwillich SH: A phase IIb doseranging study of the oral JAK inhibitor tofacitinib (CP690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum 2012, 64(4):970-981.
  • [19]Tanaka Y, Suzuki M, Nakamura H, Toyoizumi S, Zwillich SH: Phase II study of tofacitinib (CP690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthrit Care Res 2011, 63(8):1150-1158.
  • [20]Fanelli D: How many scientists fabricate and falsify research? a systematic review and meta-analysis of survey data. PLoS One 2009, 4(5):e5738.
  • [21]Orme ME, MacGilchrist KS, Mitchell S, Spurden D, Bird A: Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70. BTT 2012, 6:429-464.
  • [22]Salliot C, van der Heijde D: Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 2009, 68(7):1100-1104.
  • [23]McLean-Tooke A, Aldridge C, Waugh S, Spickett GP, Kay L: Methotrexate, rheumatoid arthritis and infection risk—what is the evidence? Rheumatology 2009, 48:867-871.
  • [24]Greenberg SB: Infections in the immunocompromised rheumatologic patient. Crit Care Clin 2002, 18:931-956.
  • [25]Gilani STA, Khan DA, Khan FA, Ahmed M: Adverse effects of low dose methotrexate in rheumatoid arthritis patients. JCPSP 2012, 22(2):101-104.
  • [26]Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE: Predictors of infection in rheumatoid arthritis. Arthritis Rheum 2002, 46(9):2294-2300.
  • [27]Ruyssen-Witrand A, Fautrel B, Saraux A, Le-LoÃet X, Pham T: Infections induced by low-dose corticosteroids in rheumatoid arthritis: a systematic literature review. Joint Bone Spine 2010, 77:246-251.
  • [28]McInnes IB, Kim H, Lee S, Mandel D, Song Y, Connell CA, Luo Z, Brosnan MJ, Zuckerman A, Zwillich SH, Bradley JD: Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study. Ann Rheum Dis 2013, 0:1-8.
  • [29]Walker E, Hernandez AV, kattan m W: Meta-analysis: its strengths an meta-analysis: its strengths and limitations. Clev Clin J Med 2008, 75(6):431-439.
  • [30]Lexchin J, Bero LA, Djulbegovic B, Clark O: Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 2003, 326:1167.
  • [31]Sismondo S: Pharmaceutical company funding and its consequences: a qualitative systematic review. Contemp Clin Trials 2008, 25:109-113.
  文献评价指标  
  下载次数:15次 浏览次数:2次