Summary
Abstract
Etanercept, a fusion protein consisting of the extracellular ligand-binding domain of the 75kD receptor for tumour necrosis factor-α and the constant portion of human IgG1, is administered by subcutaneous injection and is the first specific anti-cytokine therapy approved for rheumatoid arthritis.
In patients with active rheumatoid arthritis [American College of Rheumatology (ACR) functional class I to III] who had failed to respond to previous treatment with ≥1 disease-modifying antirheumatic drug (DMARD), etanercept, alone or in combination with methotrexate, produced improvements in all components included in the ACR core set of disease activity measures.
A dose-response effect was apparent with etanercept 0.25 to 16 mg/m2 twice weekly in a randomised, double-blind study in 180 patients. The mean number of swollen or tender joints at the end of the 12-week study decreased by >50% in patients treated with etanercept 16 mg/m2 twice weekly and by >25% in patients treated with placebo.
In a 24-week multicentre, randomised, double-blind study in 234 patients who were not allowed to use DMARDs, etanercept 10 or 25mg twice weekly had a rapid onset of effect. Significantly more patients treated with etanercept 25mg twice weekly than placebo experienced 20 (ACR 20), 50 (ACR 50) or 70% (ACR 70) improvement in ACR criteria after 3 and 6 months. Limited evidence suggests that the therapeutic effects of etanercept are maintained for up to 2 years.
Etanercept 25mg twice weekly produced significant improvement in patients receiving oral or subcutaneous methotrexate 10 to 25 mg/week in a multicentre, randomised, double-blind, placebo-controlled study. A significantly greater proportion of patients treated with etanercept plus methotrexate (71%) than placebo plus methotrexate (27%) achieved the ACR 20 criteria after 6 months. Moreover, 39 and 15% of patients treated with etanercept plus methotrexate, but no placebo plus methotrexate recipients, had achieved the ACR 50 and ACR 70 criteria at this time.
Etanercept 0.4 mg/kg twice weekly reduced disease activity in a preliminary, noncomparative study in 69 children aged ≥4 years with refractory juvenile rheumatoid arthritis.
Although the overall frequency of infections was similar in patients treated with etanercept or placebo, upper respiratory tract infections were more common in patients treated with etanercept (29%) than placebo (16%). Injection site reactions occurred more frequently in etanercept-than placebo-treated patients, but did not bias the results of any study.
Conclusions: When etanercept is administered alone or in combination with methotrexate in patients with refractory rheumatoid arthritis, significant reductions in disease activity occur within 2 weeks and are sustained for at least 6 months. Thus, etanercept appears to be particularly well suited for use in patients who fail to respond to treatment with DMARDs.
References
McQueen FM, Stewart N, Crabbe J, et al. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset. Ann Rheum Dis 1998; 57: 350–6
van der Heijde DMFM. Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol 1995; 34 Suppl. 2: 74–8
Kingsley G, Panayi GS. Joint destruction in rheumatoid arthritis: biological bases. Clin Exp Rheumatol 1997; 15 Suppl. 17: S3–14
Buckley CD. Treatment of rheumatoid arthritis. BMJ 1997 Jul 26; 315: 236–8
Firestein GS, Zvaifler NJ. Anticytokine therapy in rheumatoid arthritis. N Engl J Med 1997 Jul 17; 337: 195–7
O’Dell JR. Anticytokine therapy — a new era in the treatment of rheumatoid arthritis? N Engl J Med 1999 Jan 28; 340: 310–2
Eigler A, Sinha B, Hartmann G, et al. Taming TNF: strategies to restrain this proinflammatory cytokine. Immunol Today 1997; 18: 487–92
Deleuran BW. Cytokines in rheumatoid arthritis: localization in arthritic joint tissue and regulation in vitro. Scand J Rheumatol 1996; 25 Suppl. 104: 1–38
Firestein GS. Invasive fibroblast-like synoviocytes in rheumatoid arthritis: passive responders or transformed aggressors? Arthritis Rheum 1996; 39: 1781–90
Feldmann M, Brennan FM, Williams RO, et al. Cytokine expression and networks in rheumatoid arthritis: rationale for anti-TNFα antibody therapy and its mechanism of action. J Inflammation 1996; 47: 90–6
Paleolog E. Target effector role of vascular endothelium in the inflammatory response: insights from the clinical trial of anti-TNFα antibody in rheumatoid arthritis. J Clin Pathol — Mol Pathol 1997; 50: 225–33
Starkebaum G. Role of cytokines in rheumatoid arthritis. Sci Med 1998 Mar–Apr; 5: 6–15
McQueen FM. The use of biologies in the treatment of rheumatoid arthritis (RA) — the good news and the bad news. Aust N Z J Med 1997; 27: 175–84
Armitage RJ. Tumor necrosis factor receptor superfamily members and their ligands. Curr Opin Immunol 1994; 6: 407–13
Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med 1996; 334: 1717–25
Cope AP. Regulation of autoimmunity by proinflammatory cytokines. Curr Opin Immunol 1998; 10: 669–76
Jones EY, Stuart DI, Walker NPC. Structure of tumour necrosis factor. Nature 1989 Mar 16; 338: 225–8
Poltorak A, Peppel K, Beutler B. Receptor-mediated label-transfer assay (RELAY): a novel method for the detection of plasma tumor necrosis factor at attomolar concentrations. J Immunol Methods 1994; 169: 93–9
Maury CPJ, Teppo A-M. Cachectin/tumour necrosis factor-α in the circulation of patients with rheumatic disease. Int J Tissue React 1989; XI(4): 189–93
Saxne T, Palladino MAJ, Heinegard D, et al. Detection of tumor necrosis factor (X but not tumor necrosis factor β in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum 1988; 31: 1041–5
Barrera P, Boerbooms AMT, Janssen EM, et al. Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor a, and interleukin-6 levels in rheumatoid arthritis: longitudinal evaluation during methotrexate and azathioprine therapy. Arthritis Rheum 1993; 36: 1070–9
Beckham JC, Caldwell DS, Peterson BL, et al. Disease severity in rheumatoid arthritis: relationships of plasma tumor necrosis factor-α, soluble interleukin 2-receptor, soluble CD4/CD8 ratio, neopterin, and fibrin D-dimer to traditional severity and functional measures. J Clin Immunol 1992; 12: 353–61
Thornton SC, Por SB, Penny R, et al. Identification of the major fibroblast growth factors released spontaneously in inflammatory arthritis as platelet derived growth factor and tumour necrosis factor-alpha. Clin Exp Immunol 1991; 86: 79–86
Husby G, Williams Jr RC. Synovial localization of tumor necrosis factor in patients with rheumatoid arthritis. J Autoimmunity 1988; 1: 363–71
Chu CQ, Field M, Feldmann M, et al. Localization of tumor necrosis factor (X in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis. Arthritis Rheum 1991; 34: 1125–32
Alvaro-Gracia JM, Zvaifler NJ, Firestein GS. Cytokines in chronic inflammatory arthritis. V. Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on HLA-DR expression, proliferation, collagenase production, and granulocyte macrophage colony-stimulating factor production by rheumatoid arthritis synoviocytes. J Clin Invest 1990; 86: 1790–8
Shingu M, Nagai Y, Isayama T, et al. The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells. Clin Exp Immunol 1993; 94: 145–9
Macnaul KL, Chartrain N, Lark M, et al. Differential effects of IL-1 and TNF alpha on the expression of stromelysin, collagenase and their inhibitor, TIMP, in rheumatoid human synovial fibroblasts. Matrix Suppl 1992; 1: 198–9
Ahmadzadeh N, Shingu M, Nobunaga M. The effect of recombinant tumor necrosis factor-ot on Superoxide and metal-loproteinase production by synovial cells and chondrocytes. Clin Exp Rheumatol 1990; 8: 387–91
Dayer JM, Beutler B, Cerami A. Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by synovial cells and dermal fibroblasts. J Exp Med 1985; 162: 2163–8
Saklatvala J. Tumour necrosis factor α stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 1986; 322: 547–9
Bertolini DR, Nedwin GE, Bringman TS, et al. Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature 1986; 319: 516–8
Brennan FMB, Chantry D, Jackson A, et al. Inhibitory effect of TNFα antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 1989 Jul 29; II: 244–7
van Lent PLEM, van de Loo FAJ, Holthuysen AEM, et al. Major role for interleukin 1 but not for tumor necrosis factor in early cartilage damage in immune complex arthritis in mice. J Rheumatol 1995; 22: 2250–8
Keffer J, Probert L, Cazlaris H, et al. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 1991; 10: 4025–31
Piguet PF, Grau GE, Vesin C, et al. Evolution of collagen arthritis in mice is arrested by treatment with anti-tumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor. Immunology 1992; 77: 510–4
Williams RO, Mason LJ, Feldmann M, et al. Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis. Proc Natl Acad Sci USA 1994; 91: 2762–6
Williams RO, Feldmann M, Maini RN. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A 1992; 89: 9784–8
Joosten LAB, Helsen MMA, van de Loo FAJ, et al. Anti-cytokine treatment of established type II collagen-induced arthritis in DBA/1 mice. Arthritis Rheum 1996; 39: 797–809
Elliott MJ, Maini RN, Feldmann M, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor a. Arthritis Rheum 1993; 36: 1681–90
Deleuran BW, Chu C-Q, Field M, et al. Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis: implications for local actions of tumor necrosis factor α. Arthritis Rheum 1992; 35: 1170–8
Butler DM, Feldmann M, Di Padova F, et al. p55 and p75 tumor necrosis factor receptors are expressed and mediate common functions in synovial fibroblasts and other fibroblasts. Eur Cytokine Netw 1994; 5: 441–8
Seckinger P, Isaaz S, Dayer JM. A human inhibitor of tumor necrosis factor alpha. J Exp Med 1988; 167: 1511–6
Olsson I, Lantz M, Nilsson E, et al. Isolation and characterization of a tumor necrosis factor binding protein from urine. Eur J Haematol 1989; 42: 270–5
Engelmann H, Aderka D, Rubinstein M, et al. A tumor necrosis factor-binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity. J Biol Chem 1989; 264: 11974–80
Ferrante A, Hauptmann B, Seckinger P, et al. Inhibition of tumour necrosis factor alpha (TNF-α)-induced neutrophil respiratory burst by a TNF inhibitor. Immunology 1991; 72: 440–2
Cope AP, Aderka D, Doherty M, et al. Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum 1992; 35: 1160–9
Heilig B, Wermann M, Gallati H, et al. Elevated TNF receptor plasma concentrations in patients with rheumatoid arthritis. Clin Invest 1992; 70: 22–7
Roux-Lombard P, Punzi L, Hasler F, et al. Soluble tumor necrosis factor receptors in human inflammatory synovial fluids. Arthritis Rheum 1993; 36: 485–9
Taylor DJ. Cytokine combinations increase p75 tumor necrosis factor receptor binding and stimulate receptor shedding in rheumatoid synovial fibroblasts. Arthritis Rheum 1994; 37: 232–5
Enbrel Prescribing Information. Immunex Corporation, Seattle, Washington, USA, NOv 1998
Fisher Jr CJ, Agosti JM, Opal SM, et al. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. N Engl J Med 1996 Jun 27; 334: 1697–702
Eason JD, Pascual M, Wee S, et al. Evaluation of recombinant human soluble dimeric tumor necrosis factor receptor for prevention of OKT3-associated acute clinical syndrome. Transplantation 1996; 61(2): 224–8
Novak EJ, Blosch CM, Perkins JD, et al. Recombinant human tumor necrosis factor receptor Fc fusion protein therapy in kidney transplant recipients undergoing OKT3 induction therapy. Transplantation 1998 Dec 27; 66: 1732–5
Du Bois J, Trehu E, Mier J, et al. Randomized placebo controlled clinical trial of high-dose interleukin-2 (IL-2) in combination with the soluble TNF receptor IgG chimera (TNFR:Fc) [abstract no. 704]. Proc Am Soc Clin Oncol 1995 Mar; 14: 258
Bozkurt B, Torre-Amione G, Soran OZ, et al. Results of amulti-dose phase I trial with tumor necrosis factor receptor (p75) fusion protein (Etanercept) in patients with heart failure [abstract no. 1110-14]. J Am Coll Cardiol 1999 Feb; 33 Suppl. A: 184A
Mohler KM, Torrance DS, Smith CA, et al. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 1993; 151: 1548–61
Jacobs CA, Beckmann MP, Mohler K, et al. Pharmacokinetic parameters and biodistribution of soluble cytokine receptors. Int Rev Exp Pathol 1993; 34B: 123–35
Wee S, Pascual M, Eason JD, et al. Biological effects and fate of a soluble, dimeric, 80-kDa tumor necrosis factor receptor in renal transplant recipients who receive OKT3 therapy. Transplantation 1997 Feb 27; 63: 570–7
Wooley PH, Dutcher J, Widmer MB, et al. Influence of a recombinant human soluble tumor necrosis factor receptor FC fusion protein on type II collagen-induced arthritis in mice. J Immunol 1993; 151: 6602–7
Moreland LW, Bucy RP, Weinblatt ME, et al. Effects of TNF receptor (P75) fusion protein (TNFR:Fc;Enbrel) on immune function [abstract no. 158]. Arthritis Rheum 1998; 41 Suppl.: S59
Chatham WW, McDuffie D, Zhang L, et al. Effects of rhuTNFR:Fc on neutrophil function [abstract]. Arthritis Rheum 1997 Sep; 40 Suppl.: S81
Nam MH, Reda D, Boujoukos AJ, et al. Recombinant human dimeric tumor necrosis factor (TNF) receptor (TNFR:Fc): safety and pharmacokinetics in human volunteers. Clin Res 1993; 41(2): 249A
Lebsack ME, Hanna RK, Lange MA, et al. Absolute bioavailability of TNF receptor fusion protein following subcutaneous injection in healthy volunteers [abstract]. Pharmacotherapy 1997 Sep–Oct; 17: 1118–9
Moreland LW, Margolies G, Heck JLW, et al. Recombinant soluble tumor necrosis factor receptor (p80) fusion protein: toxicity and dose finding trial in refractory rheumatoid arthritis. J Rheumatol 1996 Nov; 23: 1849–55
Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997 Jul 17; 337: 141–7
Weinblatt ME, Kremer JM, Bankhurst AD, et al. A trial of Etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999 Jan 28; 340: 253–9
Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled study. Ann Intern Med 1999; 130: 478–86
Hochberg MC, Chang RW, Dwosh I, et al. American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum 1992; 35: 498–502
Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995; 38: 727–35
Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum 1993; 36: 729–40
Epstein WV. Expectation bias in rheumatoid arthritis clinical trials: the anti-CD4 monoclonal antibody experience. Arthritis Rheum 1996 Nov; 39: 1773–80
Epstein WV. Treatment of rheumatoid arthritis with a tumor necrosis factor receptor-Fc fusion protein [letter and discussion]. N Engl J Med 1997 Nov 20; 337: 1559–61
Moreland LW, Widmer MB, Blosch CM. Treatment of rheumatoid arthritis with a tumor necrosis factor receptor-Fc fusion protein [reply: letter]. N Engl J Med 1997; 337: 1560–1
Baumgartner SW, Moreland LW, Schiff MH, et al. Response of elderly patients to the TNF receptor p75 FC fusion protein (TNFR:FC; Enbrel) [abstract no. 160]. Arthritis Rheum 1998; 41 Suppl.: S59
Moreland L, Blosch C, Colwell H, et al. Functioning and well-being of DMARD-failed rheumatoid arthritis patients receiving P75 TNFR:FC (Enbrel) [abstract no. 159]. Arthritis Rheum 1998; 41 Suppl.: S59
Moreland LW, Baumgartner SW, Tindall EA, et al. Long term safety and efficacy of Etanercept (Enbrel) in DMARD refractory rheumatoid arthritis (RA) [abstract]. XIV European League Against Rheumatism (EULAR) Congress; 1999 Jun 6–11; Glasgow
Lovell DJ, Giannini EH, Whitmore JB, et al. Safety and efficacy of tumor necrosis factor receptor p75 FC fusion protein (TNFR:FC; Enbrel) in polyarticular course juvenile rheumatoid arthritis [abstract no. 584]. Arthritis Rheum 1998; 41 Suppl.: S130
Giannini EH, Ruperto N, Ravelli A, et al. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 1997; 40: 1202–9
Terranova PF, Hunter VJ, Roby KF, et al. Tumor necrosis factor-α in the female reproductive tract. Proc Soc Exp Biol Med 1995; 209: 325–42
Robertson SA, Seamark RF, Guilbert LJ, et al. The role of cytokines in gestation. Crit Rev Immunol 1994; 14: 239–92
Pincus T. Long term outcomes in rheumatoid arthritis. Br J Rheumatol 1995 Nov; 34 Suppl. 2: 59–73
Callahan LF. The burden of rheumatoid arthritis: facts and figures. J Rheumatol 1998 Jul; 25 Suppl. 53: 8–12
Mclntosh E. The cost of rheumatoid arthritis. Br J Rheumatol 1996; 35: 781–90
Yelin E. The costs of rheumatoid arthritis: absolute, incremental, and marginal estimates. J Rheumatol 1996; 23 Suppl. 44: 47–51
Wolfe F, Kleinheksel SM, Spitz PW, et al. A multicenter study of hospitalization in rheumatoid arthritis: effect of health care system severity and regional difference. J Rheumatol 1986; 13: 277–84
American College of Rheumatology Ad Hoc Committee On Clinical Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis Rheum 1996; 39: 713–22
Fries JF, Miller SR, Spitz PW, et al. Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use. Gastroenterology 1989; 96: 647–55
Fries JF, Williams CA, Bloch DA, et al. Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factor models. Am J Med 1991; 91: 213–22
Kirwan JR, The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 1995; 333: 142–6
Hickling P, Jacoby RK, Kirwan JR, et al. Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Br J Rheumatol 1998; 37: 930–6
Yocum DE. Glucocorticoids in rheumatoid arthritis: lessons for the future. Br J Rheumatol 1998; 37: 1145–7
Weinblatt ME. Rheumatoid arthritis: treat now, not later! Ann Intern Med 1996; 124: 773–4
Jain R, Lipsky PE. Treatment of rheumatoid arthritis. Adv Rheumatol 1997; 81: 57–84
van Gestel AM, Haagsma CJ, Furst DE, et al. Treatment of early rheumatoid arthritis patients with slow-acting anti-rheumatic drugs (SAARDS). Baillieres Clin Rheumatol 1997; 11: 65–82
Scott.DL. Clinical guidelines for management. Baillieres Clin Rheumatol 1997; 11: 157–79
Box SA, Pullar T. Sulphasalazine in the treatment of rheumatoid arthritis. Br J Rheumatol 1997 Mar; 36: 382–6
Rozman B, Leflunomide Investigators Group. Clinical experience with leflunomide in rheumatoid arthritis. J Rheumatol 1998 Jul; 25 Suppl. 53: 27–32
Gaffney K, Scott DGI. Azathioprine and cyclophosphamide in the treatment of rheumatoid arthritis. Br J Rheumatol 1998 Aug; 37: 824–36
Furst DE. The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases. Br J Rheumatol 1997 Nov; 36: 1196–204
Jones G, Brooks PM. Injectable gold compounds: an overview. Br J Rheumatol 1996 Nov; 35: 1154–8
Kean WF, Hart L, Buchanan WW. Auranofin. Br J Rheumatol 1997 May; 36: 560–72
Chaudhuri K, Torley H, Madhok R. Cyclosporin. Br J Rheumatol 1997 Sep; 36: 1016–21
Munro R, Capell HA. Penicillamine. Br J Rheumatol 1997; 36: 104–9
Rynes RI. Antimalarial drugs in the treatment of rheumatological diseases. Br J Rheumatol 1997; 36: 799–805
American College of Rheumatology Ad Hoc Committee On Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996; 39: 723–31
Anon. Arava (leflunomide) prescribing information. Hoechst Marion Roussel Inc., Kansas City, Missouri, 1998 Sep
Cash JM, Klippel JH. Second-line drug therapy for rheumatoid arthritis. N Engl J Med 1994; 330: 1368–75
Comer M, Scott DL, Doyle DV, et al. Are slow-acting anti-rheumatic drugs monitored too often? An audit of currentclinical practice. Br J Rheumatol 1995; 34: 966–70
Farr M, Bacon PA. How and when should combination therapy be used? The role of an anchor drug. Br J Rheumatol 1995 Nov; 34 Suppl. 2: 100–3
Wolfe F. Adverse drug reactions of DMARDs and DC-ARTs in rheumatoid arthritis. Clin Exp Rheumatol 1997; 15 Suppl. 17: S75–81
O’Dell J. Combination DMARD therapy for rheumatoid arthritis: apparent universal acceptance [abstract]. Arthritis Rheum 1997; 40 Suppl.: S50
Onrust SV, Lamb HM. Infliximab: a review of its use in Crohn’s disease and rheumatoid arthritis. Biodrugs 1998; 10: 397–422
Elliott MJ, Maini RN, Feldmann M, et al. Repeated therapy with monoclonal antibody to tumour necrosis factor α (cA2) in patients with rheumatoid arthritis. Lancet 1994; 344: 1125–7
Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor α monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998; 41: 1552–63
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Various sections of the manuscript reviewed by: A.P. Cope, The Kennedy Institute of Rheumatology, Immunology Division, London, England; B. Deleuran, Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; M. Dougados, Clinique de Rheumatologie, Hôpital Cochin, Paris, France; A. Eigler, Medizinische Klinik, Klinikum Innenstadt der Ludwig Maximilians Universität, Munich, Germany; S. Endres, Medizinische Klinik, Klinikum Innenstadt der Ludwig Maximilians Universität, Munich, Germany; G.S. Firestein, Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, La Jolla, California, USA; Ø. Førre, Rikshospitalet, The National Hospital, University of Oslo, Oslo, Norway; D.J. Lovell, Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA; M. Østergaard, Department of Rheumatology, Hvidovre Hospital, Hvidovre, Denmark; M. Swims, Department of Pharmacy Practice and Pharmacoeconomics, College of Pharmacy, University of Tennessee, and Veterans Affairs Medical Center, Memphis, Tennessee, USA.
Data Selection
Sources: Medical literature published in any language since 1966 on etanercept, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand), Medline and EMBASE. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: AdisBase search terms were ‘etanercept’, ‘enbrel’, ‘TNF-001’ and ‘TNFR-Fc’. Medline and EMBASE search terms were ‘etanercept’, ‘enbrel’, ‘TNF-001’ and ‘TNFR-Fc’. Searches were last updated 10 May, 1999.
Selection: Studies in patients with rheumatoid arthritis who received etanercept. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: etanercept, pharmacodynamics, pharmacokinetics, rheumatoid arthritis, therapeutic use.
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Jarvis, B., Faulds, D. Etanercept. Drugs 57, 945–966 (1999). https://doi.org/10.2165/00003495-199957060-00014
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DOI: https://doi.org/10.2165/00003495-199957060-00014