Intravenous human recombinant tumor necrosis factor receptor p55-Fc IgG1 fusion protein Ro 45-2081 (lenercept): A double blind, placebo controlled dose-finding study in rheumatoid arthritis

Journal of Rheumatology

Volumn 30, Issue 4, 2003, Pages 680-690

  Rau, Rolf ^a   Sander, Oliver ^a   Van Riel, Piet ^b   Van de Putte, Leo ^b   Hasler, Fritz ^c   Zaug, Michel ^d   Kneer, Johannes ^d   Van der Auwera, Philippe ^d   Stevens, Randall M ^e   Baudin, M ^a   Dickson, S ^a   Herbold, D ^a   Kaehny, M R ^a   Luedin, E ^a   McAuliffe, T ^a  

^a Evangelisches Fachkrankenhaus ^*

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^c Arthritis Research Unit   (Switzerland)

^d Novartis Pharma   (Switzerland)

^e Clinical Science   (United States)

Author keywords

Antibody formation; Controlled trial; Rheumatoid arthritis; Ro 45 2081; Tumor necrosis factor receptor fusion protein

Indexed keywords

ACUTE PHASE PROTEIN; ANTIBODY; ANTIINFLAMMATORY AGENT; ANTIRHEUMATIC AGENT; AURANOFIN; AUROTHIOGLUCOSE; AUROTHIOMALATE; AZATHIOPRINE; CHLOROQUINE; CORTICOSTEROID DERIVATIVE; CYCLOPHOSPHAMIDE; CYCLOSPORIN; HYDROXYCHLOROQUINE; LENERCEPT; METHOTREXATE; NONSTEROID ANTIINFLAMMATORY AGENT; PENICILLAMINE; PLACEBO; SALAZOSULFAPYRIDINE;

ADULT; AGED; ANEMIA; ARTICLE; BACKACHE; CLINICAL TRIAL; CONCENTRATION (PARAMETERS); CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE ACTIVITY; DOSE CALCULATION; DOUBLE BLIND PROCEDURE; DRUG CLEARANCE; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; EDEMA; EROSIVE GASTRITIS; FEMALE; HEADACHE; HUMAN; INFLUENZA; LEG EDEMA; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; PAIN; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN INTERACTION; RHEUMATOID ARTHRITIS; SIDE EFFECT; STATISTICAL ANALYSIS; STOMACH PAIN; TIME;

ADULT; AGED; ANTIBODIES; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOGLOBULIN GAMMA-CHAINS; IMMUNOGLOBULIN HEAVY CHAINS; INFECTION; INJECTIONS, INTRAVENOUS; MALE; MIDDLE AGED; PLACEBOS; RECEPTORS, TUMOR NECROSIS FACTOR; RECOMBINANT FUSION PROTEINS; TREATMENT OUTCOME;

EID: 12444335752     PISSN: 0315162X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (37)

1. Brooks PM. Clinical management of rheumatoid arthritis. Lancet 1993;341:286-90.
2. Pincus T. The paradox of effective therapies but poor long-term outcome in rheumatoid arthritis. Semin Arthritis Rheum 1992;21 Suppl 3:2-15.
3. Scott DL, Symmons DPM, Coulton BL, Popert AJ. Long-term outcome of treating rheumatoid arthritis: Results after 20 years. Lancet 1987;1:1108-11.
4. Brennan FM, Maini RN, Feldmann M. TNF-α: a pivotal role in rheumatoid arthritis? Br J Rheumatol 1992;31:293-8.
5. Dayer JM, Fenner H. The role of cytokines and their inhibitors in arthritis. Baillieres Clin Rheumatol 1992;6:485-516.
6. Feldmann M, Brennan FM, Chantry D, et al. Cytokine production in the rheumatoid joint: implications for treatment. Ann Rheum Dis 1990;49:480-6.
7. Saxne T, Palladino MA, Heinegard D, Talal N, Wollheim FA. Detection of tumor necrosis factor α, but not tumor necrosis factor β in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum 1988;31:1041-5.
8. Elliott MJ, Maini RN, Feldmann M, et al. Treatment of rheumatoid arthritis with chimaeric monoclonal antibodies to tumour necrosis factor α. Arthritis Rheum 1993;36:1681-90.
9. Elliott MJ, Maini RN, Feldmann M, et al. Randomized double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994;344:1105-10.
10. 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.
11. Rankin ECC, Choy EHS, Kassimos D, et al. The therapeutic effects of an engineered human anti-mmour necrosis factor alpha antibody (CDP571) in rheumatoid arthritis. Br J Rheumatol 1995;34:334-42.
12. Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998;41:1552-63.
13. Lipsky PE, van der Heijde D, St. Clair W, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 2000;343:1594-602.
14. 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;337:141-7.
15. Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intem Med 1999;130:478-86.
16. 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;340:253-9.
17. Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. New Engl J Med 2000;343:1586-93.
18. Rau R, Herborn G, Sander O, et al. Long-term treatment with the fully human anti-TNF antibody D2E7 slows radiographic disease progression in rheumatoid arthritis [abstract]. Arthritis Rheum 1999;42 Suppl:S400.
19. Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: Two-year radiographic and clinical outcomes. Arthritis Rheum 2002;46:1443-50.
20. Lesslauer W, Tabuchi H, Gentz R, et al. Recombinant soluble TNF receptor proteins protect mice from LPS-induced lethality. Eur J Immunol 1991;21:2883-6.
21. Ashkenazy A, Marsters SA, Capon DJ, et al. Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin. Proc Natl Acad Sci USA 1991;88:10535-9.
22. Hasler F, van de Putte L, Dumont E, et al. Safety and efficacy of TNF neutralization by lenercept in patients with rheumatoid arthritis exposed to a single dose [abstract]. Arthritis Rheum 1996;39 Suppl:S243.
23. Hasler F, van de Putte L, Baudin M, et al. Chronic TNF neutralization (up to I year) by lenercept (TNFR 55 IgG 1, Ro 45-2081) in patients with rheumatoid arthritis: Results for open label extension of a double-blind single-dose phase I study [abstract]. Arthritis Rheum 1996;39 Suppl:S243.
24. Sander O, Rau R, van Riel P, et al. Neutralization of TNF by lenercept (TNFR55-IgG1, Ro 45-2081) is associated with a dose-dependent reduction in disease activity in patients with rheumatoid arthritis treated for 3 months [abstract]. Rheumatol Eur 1996;25:S1,52.
25. Sander O, Rau R, van Riel P, et al. Neutralization of TNF by lenercept (TNFR55-IgG1, Ro 45-2081) in patients with rheumatoid arthritis treated for 3 months: Results of a European Phase II trial [abstract]. Arthritis Rheum 1996;39 Suppl:S242.
26. Furst D, Weisman M, Paulus H, et al. Neutralization of TNF by lenercept (TNFR 55 TgGt, Ro 45-2081) in patients with rheumatoid arthritis treated for 3 months: Results of a phase II trial [abstract]. Arthritis Rheum 1996;39 Suppl:S243.
27. Boers M, Tugwell P, Felson DT, et al. WHO and ILAR core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis trials. J Rheumatol 1994;21 Suppl 41:86-9.
28. Margolin BH. Test for trend in proportions. In: Johnson N, Kotz S, editors. Encyclopedia of statistical sciences. New York: John Wiley & Sons; 1988:334-6.
29. Furst DE. Considerations on measuring decreased synovitis. Fifth Joint WHO/ILAR Task Force Meeting on Rheumatic Diseases. ILAR Bulletin 1994;2:17-21.
30. Garcia I, Miyazaki Y, Araki K, et al. Transgenic mice expressing high levels of soluble TNF-R1 fusion protein are protected from lethal septic shock and cerebral malaria, and are highly sensitive to Listeria monocytogenes and Leishmania major infections. Eur J Immunol 1995;25:2401-7.
31. Garcia I, Miyazaki Y, Marchal G, Lesslauer W, Vassalli P. High sensitivity of transgenic mice expressing soluble TNFR1 fusion protein to mycobacterial infections: synergistic action of TNF and IFN-γ in the differentiation of protective granulomas. Eur J Immunol 1997;27:3182-90.
32. Havell EA. Evidence that tumour necrosis factor has an important role in antibacterial resistance. J Immunol 1989;143:2894-9.
33. Pfeffer K, Matsuyama T, Kuendig TM, et al. Mice deficient for the 55kd tumour necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 1993;73:457-67.
34. Rothe J, Lesslauer W, Loetscher H, et al. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 1993;364:798-802.
35. Abraham E, Laterre PF, Garbino J, et al. Lenercept (p55-tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: A randomized, double-blind, placebo-controlled multicenter phase III trial with 1342 patients. Crit Care Med 2001;29:503-10.
36. The Lenercept Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. TNF neutralization in MS. Results of a randomized, placebo-controlled multicenter study. Neurology 1999;53:457-65.
37. Kneer J, Dumont E, Bimboeck H, Kusano T, Gallati H, Lesslauer W. A new TNF-neutralizing agent - lenercept (TNFR55-IgG1, Ro 45-2081): pharmacokinetic/dynamic data over a 100-fold dose range in healthy volunteers [abstract]. Rheumatol Eur 1996;25:S1,52.