Adalimumab - A new TNF-α antibody for treatment of inflammatory joint disease

Expert Opinion on Biological Therapy

Volumn 3, Issue 2, 2003, Pages 351-360

  Machold, Klaus P ^a   Smolen, Josef S ^a  

^a UNIVERSITY OF VIENNA   (Austria)

Author keywords

Adalimumab; D2E7; Inflammation; Monoclonal antibody; Rheumatoid arthritis; Rheumatology; TNF

Indexed keywords

ADALIMUMAB; ALKALINE PHOSPHATASE; ANTIRHEUMATIC AGENT; ETANERCEPT; INFLIXIMAB; METHOTREXATE; RECOMBINANT ANTIBODY; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA ANTIBODY;

ABDOMINAL PAIN; BACKACHE; CLINICAL TRIAL; CYTOKINE PRODUCTION; DRUG BINDING; DRUG EFFICACY; DRUG INHIBITION; DRUG MARKETING; DRUG SAFETY; DRUG TOLERABILITY; FEVER; FLU LIKE SYNDROME; HEADACHE; HEMATURIA; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; HYPERTENSION; IC 50; NAUSEA; NONHUMAN; QUALITY OF LIFE; RADIODIAGNOSIS; RASH; REVIEW; RHEUMATOID ARTHRITIS; SIDE EFFECT; SINGLE DRUG DOSE; SINUSITIS; TREATMENT OUTCOME; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION;

ANIMALS; ANTIBODIES, MONOCLONAL; ARTHRITIS; ARTHRITIS, RHEUMATOID; CLINICAL TRIALS; COMBINED MODALITY THERAPY; DISEASE PROGRESSION; HUMANS; TUMOR NECROSIS FACTOR-ALPHA;

MAMMALIA;

EID: 0037393418     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/eobt.3.2.351.21148     Document Type: Review

References (91)

1. FELSON DT: Epidemiology of the rheumatic diseases. In: Arthritis and Allied Conditions, 14th Edition. Koopman WJ (Ed.), Lippincott Williams & Wilkins (2001):3-38.
2. BRENNAN FM, MAINI RN, FELDMANN M: TNFα - a pivotal role in rheumatoid arthritis? Br. J. Rheumatol. (1992) 31:293-298. An overview over the role of TNF-α in inflammation pathology with regard to RA.
3. AREND WP, DAYER JM: Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. (1990) 33:305-315.
4. WEINBLATT ME, REDA D, HENDERSON W et al.: Sulfasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials. J. Rheumatol. (1999) 26:2123-2130.
5. VAN DER HEIJDE DM, VAN RIEL PL, NUVER-ZWART IH, GRIBNAU FW, VAN DE PUTTE LB: Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet (1989) 1:1036-1038.
6. FORRE O: Radiologic evidence of disease modification in rheumatoid arthritis patients treated with cyclosporine. Results of a 48-week multicenter study comparing low-dose cyclosporine with placebo. Norwegian Arthritis Study Group. Arthritis Rheum. (1994) 37:1506-1512.
7. DROSOS AA, VOULGARI PV, KATSARAKI A, ZIKOU AK: Influence of cyclosporin A on radiological progression in early rheumatoid arthritis patients: a 42-month prospective study. Rheumatol. Int. (2000) 19:113-118.
8. WEINBLATT ME: Efficacy of methotrexate in rheumatoid arthritis. Br. J. Rheumatol. (1995) 34(Suppl. 2):43-48.
9. SANDERS M: A review of controlled clinical trials examining the effects of antimalarial compounds and gold compounds on radiographic progression in rheumatoid arthritis. J. Rheumatol. (2000) 27:523-529.
10. CAPELL A: Clinical efficacy of sulphasalazine - a review. Br. J. Rheumatol. (1995) 34(Suppl. 2):35-39.
11. SMOLEN JS, KALDEN JR, SCOTT DL et al.: Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomized, multicentre trial. The European Leflunomide Study Group. Lancet (1999) 353:259-265.
12. ALETAHA D, SMOLEN JS: Effectiveness profiles and dose dependent retention of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. An observational study. J. Rheumatol. (2002) 29:1631-1638.
13. PALEOLOG EM, DELASALLE SA, BUURMAN WA, FELDMANN M: Functional activities of receptors for tumor necrosis factor-alpha on human vascular endothelial cells. Blood (1994) 84:2578-2590.
14. RYFFEL B, BROCKHAUS M, GREINER B, MIHATSCH MJ, GUDAT F: Tumour necrosis factor receptor distribution in human lymphoid tissue. Immunology (1991) 74:446-452.
15. RYFFEL B, MIHATSCH MJ: TNF receptor distribution in human tissues. Int. Rev. Exp. Pathol. (1993) 34(Pt B):149-156.
16. BRADLEY JR, THIRU S, POBER JS: Disparate localization of 55-kd and 75-kd tumor necrosis factor receptors in human endothelial cells. Am. J. Pathol. (1995) 146:27-32.
17. DYBEDAL I, BRYDER D, FOSSUM A, RUSTEN LS, JACOBSEN SE: Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor negatively regulates maintenance of cycling reconstituting human hematopoietic stem cells. Blood (2001) 98:1782-1791.
18. GRUSCHWITZ MS, ALBRECHT M, VIETH G, HAUSTEIN UF: In situ expression and serum levels of tumor necrosis factor-alpha receptors in patients with early stages of systemic sclerosis. J. Rheumatol. (1997) 24:1936-1943.
19. KOSKI H, JANIN A, HUMPHREYS-BEHER MG, SORSA T, MALMSTROM M, KONTTINEN YT: Tumor necrosis factor-alpha and receptors for it in labial salivary glands in Sjogren's syndrome. Clin. Exp. Rheumatol. (2001) 19:131-137.
20. ALSALAMEH S, WINTER K, AL-WARD R, WENDLER J, KALDEN JR, KINNE RW: Distribution of TNF-alpha, TNF-R55 and TNF-R75 in the rheumatoid synovial membrane: TNF receptors are localized preferentially in the lining layer, TNF-alpha is distributed mainly in the vicinity of TNF receptors in the deeper layers. Scand. J. Immunol. (1999) 49:278-285.
21. DELEURAN BW, CHU CQ, FIELD M et al.: Localization of tumor necrosis factor receptors in the synovial tissue and cartilagepannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor alpha. Arthritis Rheum. (1992) 35:1170-1178.
22. STEELE IC, NUGENT AM, MAGUIRE S et al.: Cytokine profile in chronic cardiac failure. Eur. J. Clin. Invest. (1996) 26:1018-1022.
23. KRISTENSEN M, CHU CQ, EEDY DJ, FELDMANN M, BRENNAN FM, BREATHNACH SM: Localization of tumour necrosis factor-alpha (TNF-alpha) and its receptors in normal and psoriatic skim epidermal cells express the 55- kD but not the 75-kD TNF receptor. Clin. Exp. Immunol. (1993) 94:354-362.
24. FELDMANN M, BRENNAN FM, CHANTRY D et al.: Cytokine production in the rheumatoid joint: implications for treatment. Ann. Rheum. Dis. (1993) 49:480-486.
25. PALEOLOG EM, HUNT M, ELLIOTT MJ, FELDMANN M, MAINI RN, WOODY JN: Deactivation of vascular endothelium by monoclonal antitumor necrosis factor alpha antibody in rheumatoid arthritis. Arthritis Rheum. (1996) 39:1082-1091.
26. CHU CQ, FIELD M, FELDMANN M, MAINI RN: Localization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis. Arthritis Rheum. (1991) 34:1125-1132.
27. SAXNE T, PALLADINO MA JR, HEINEGARD D, TALAL N, WOLLHEIM FA: Detection of tumor necrosis factor alpha but not tumor necrosis factor beta in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum. (1988) 31:1041-1045.
28. BRENNAN FM, CHANTRY D, JACKSON A, MAINI R, FELDMANN M: Inhibitory effect of TNF alpha antibodies on synovial cell interleukin- 1 production in rheumatoid arthritis. Lancet (1989) 2:244-247.
29. HAWORTH C, BRENNAN FM, CHANTRY D, TURNER M, MAINI RN, FELDMANN M: Expression of granulocytemacrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur. J. Immunol. (1991) 21:2575-2579.
30. THORBECKE GJ, SHAH R, LEU CH, KURUVILLA AP, HARDISON AM, PALLADINO MA: Involvement of endogenous tumor necrosis factor alpha and transforming growth factor beta during induction of collagen Type II arthritis in mice. Proc. Natl. Acad. Sci. USA (1992) 89:7375-7379.
31. WILLIAMS RO, FELDMANN M, MAINI RN: Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc. Natl Acad. Sci. USA (1992) 89:9784-9788.
32. ELLIOTT MJ, MAINI RN, FELDMANN M et al.: Randomised double- blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet (1994) 344:1105-1110. The first report on human application of anti-TNF therapy.
33. MAINI RN, BREEDVELD FC, KALDEN JR et al.: Therapeutic effects of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. (1998) 41:1552-1563. Description of combined efficacy of infliximab and MTX.
34. TAK PP, TAYLOR PC, BREEDVELD FC et al.: Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis. Arthritis Rheum. (1996) 39:1077-1081.
35. CHARLES P, ELLIOTT MJ, DAVIS D et al.: Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis. J. Immunol. (1999) 163:1521-1528.
36. LIPSKY PE, VAN DER HEIJDE DM, ST CLAIR EW et al.: Infliximab and methotrexate in the treatment of rheumatoid arthritis. N. Engl. J. Med. (2000) 343:1594-1602.
37. KIELY PD, JOHNSON DM: Infliximab and leflunomide combination therapy in rheumatoid arthritis: an open-label study. Rheumatology (2002) 41:631-637.
38. RIEGERT-JOHNSON DL, GODFREY JA, MYERS JL, HUBMAYR RD, SANDBORN WJ, LOFTUS EV JR: Delayed hypersensitivity reaction and acute respiratory distress syndrome following infliximab infusion. Inflamm. Bowel. Dis. (2002) 8:186-191.
39. 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) 41:1552-1563.
40. 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) 337:141-147.
41. 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) 340:253-259.
42. BATHON JM, MARTIN RW, FLEISCHMANN RM et al.: A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N. Engl. J. Med. (2000) 343:1586-1593. The only head to head comparison of MTX and a TNF antagonist.
43. BRAUN J, BRANDT J, LISTING J et al.: Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet (2002) 359:1187-1193.
44. GORMAN JD, SACK KE, DAVIS JC JR: Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N. Engl. J. Med. (2002) 346:1349-1356.
45. SALFELD J, KAYMAKCALAN Z, TRACEY D, ROBERTS A, KAMEN R: Generation of fully human anti-TNF antIbody D2E7. Arthritis Rheum. (1998) 41:S57.
46. LORENZ HM: Technology evaluation: adalimumab, Abbott laboratories. Curr. Opin. Mol. Ther. (2002) 4:185-190.
47. KAYMAKCALAN Z, KOLLIAS G, HARALAMBOUS S et al.: Development of a fully human anti-TNF monoclonal antibody. J. Interferon Cytokine Res. (1998) 18:A125.
48. SCALLON BJ, MOORE MA, TRINH H, KNIGHT DM, GHRAYEB J: Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine (1995) 7:251-259.
49. DEN BROEDER A, VAN DE PUTTE L, RAU R et al.: A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis. J. Rheumatol. (2002) 29:2288-2298. The first full original paper on adalimumab efficacy in RA.
50. DEN BROEDER AA, JOOSTEN LA, SAXNE T et al.: Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Ann. Rheum. Dis. (2002) 61:311-318. Description of the effects of adalimumab on radiological damage in RA.
51. BARRERA P, VAN DER MAAS A, VAN EDE AE et al.: Drug survival, efficacy and toxicity of monotherapy with a fully human anti-tumour necrosis factor-alpha antibody compared with methotrexate in long-standing rheumatoid arthritis. Rheumatology (2002) 41:430-439.
52. RAU R, SANDER O, DEN BROEDER A et al.: Long-term efficacy and tolerability of multiple i.v. doses of the fully human anti-TNF antibody D2E7 in patients with rheumatoid arthritis. Arthritis Rheum. (1998) 41 (Suppl.):S55.
53. SCHATTENKIRCHNER M, KRÜGER K, SANDER O et al.: Efficacy and tolerability of weekly subcutaneous injections of the fully human and TNF antibody D2E7 in patients with rheumatoid arthritis. Arthritis Rheum. (1998) 41 (Suppl.):S57.
54. FELSON DT, ANDERSON JJ, BOERS M et al.: American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. (1995) 38:727-735.
55. VAN GESTEL AM, ANDERSON JJ, VAN RIEL PL et al.: ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. American College of Rheumatology European League of Associations for Rheumatology. J. Rheumatol. (1999) 26:705-711.
56. TUGWELL P, BOERS M: OMERACT conference on outcome measures in RA clinical trials: conclusion. J. Rheumatol. (1993) 20:590.
57. VAN DE PUTTE LBA, RAU R, BREEDVELD FC et al.: Efficacy of the fully human anti-TNF antibody D2E7 in rheumatoid arthritis. Arthritis Rheum. (1999) 42(Suppl.):S400.
58. VAN DE PUTTE LBA, RAU R, BREEDVELD FC et al.: 1-year efficacy results of the fully human anti-TNF antibody D2E7 in rheumatoid arthritis. Arthritis. Rheum. (2000) 43:S269.
59. SCHATTENKIRCHNER M, VALLBRACHT I, RAU R et al.: Long-term use of the fully human anti-TNF antibody adalimumab (D2E7) in DMARD- refractory rheumatoid arthritis. Ann. Rheum. Dis. (2001) 60(Suppl.):66.
60. BURMESTER GR, VAN DE PUTTE LBA, RAU R et al.: 2-year experience with adalimumab (D2E7), the first fully human anti-TNF monoclonal antibody, in patients with DMARD-refractory rheumatoid arthritis. Ann. Rheum. Dis. (2002) 61 (Suppl. 1):206.
61. RAU R, HERBORN G, WASSENBERG S et al.: 2.5-year treatment results with adalimumab (D2E7), the first fully human anti-TNF monoclonal antibody, in combination with methotrexate in active rheumatoid arthritis. Ann. Rheum. Dis. (2002) 51(Suppl. 1):55.
62. BOERS M, RAMSDEN M: Longacting drug combinations in rheumatoid arthritis: a formal overview. J. Rheumatol. (1991) 18:316-324.
63. BUNCH TW, O'DUFFY JD, TOMPKINS RB, O'FALLON WM: Controlled trial of hydroxychloroquine and d-penicillamine singly and in combination in the treatment of rheumatoid arthritis. Arthritis Rheum. (1984) 27:267-276.
64. DOUGADOS M, SMOLEN JS: Pharmacological management of early rheumatoid arthritis-does combination therapy improve outcomes? J. Rheumatol. Suppl. (2002) 66:20-26.
65. FAARVANG KL, EGSMOSE C, KRYGER P, PODENPHANT J, INGEMAN-NIELSEN M, HANSEN TM: Hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis: a randomised double blind trial. Ann. Rheum. Dis. (1993) 52:711-715.
66. FERRAZ MB, PINHEIRO GRC, HELFENSTEIN M et al.: Combination therapy with methotrexate and chloroquine in rheumatoid arthritis. Scand. J. Rheumatol. (1994) 23:231-236.
67. LANDEWE RB, BOERS M, VERHOEVEN AC et al.: COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. (2002) 46:347-356.
68. MCCARTY DJ, CARRERA GF: Intractable rheumatoid arthritis. Treatment with combined cyclophosphamide, azathioprine, and hydroxychloroquine. JAMA (1982) 248:1718-1723.
69. MOTTONEN T, HANNONEN P, LEIRISALO-REPO M et al.: Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RA Co trial group. Lancet (1999) 353:1568-1573.
70. O'DELL JR, HAIRE CE, ERIKSON N et al.: Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N. Engl. J. Med. (1996) 334:1287-1291.
71. PINCUS T, O'DELL JR, KREMER JM: Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis: a preventive strategy. Ann. Intern. Med. (1999) 131:768-774.
72. TUGWELL P, PINCUS T, YOCUM D et al.: Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. N. Engl. J. Med. (1995) 333:137-141.
73. WALTERS MT, CAWLEY MID: Combined suppressive drug treatment in severe refractory rheumatoid disease: an analysis of the relative effects of parenteral methylprednisolone, cyclophosphamide, and sodium aurothiomalate. Ann. Rheum. Dis. (1988) 47:924-929.
74. WEINBLATT ME, KREMER JM, COBLYN JS et al.: Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis. Arthritis Rheum. (1999) 42:1322-1328.
75. WILLIAMS HJ, WARD JR, READING JC et al.: Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. Arthritis Rheum. (1992) 35:259-269.
76. WEINBLATT ME, KEYSTONE EC, FURST DE et al.: Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. (2003) 48:35-45.
77. KEYSTONE E, WEINBLATT M, FURST D et al.: The ARMADA trial: a double-blind, placebo-controlled trial of the fully human anti-TNF monoclonal antibody, adalimumab (D2E7), in patients with active RA on methotrexate (MTX). Arthritis Rheum. (2001) 44:S213.
78. KAVANAUGH AF, WEINBLATT M, KEYSTONE E et al.: The ARMADA trial: 12-month efficacy and safety of combination therapy with adalimumab (D2E7), the first fully human anti-TNF monoclonal antibody, and methotrexate (MTX) in patients with active rheumatoid arthritis. Ann. Rheum. Dis. (2002) 61(Suppl. 1):168.
79. STRAND V, WEINBLATT M, KEYSTONE E, FISCHKOFF S, CHARTASH E: Treatment with adalimumab (D2E7), a fully human anti-TNF monoclonal antibody, improves physical function and health related quality of life (HRQOL) in patients with active rheumatoid arthritis (RA). Ann. Rheum. Dis. (2002) 61 (Suppl. 1):175.
80. BREEDVELD FC, ALLAART CF, RAU R et al.: The fully human anti-TNF antibody adalimumab (D2E7) in combination with methotrexate (MTX) in the treatment of active rheumatoid arthritis: results of a 2-year study. Ann. Rheum. Dis. (2001) 60(Suppl. 1):60.
81. WEISMAN ME, KEYSTONE E, PAULUS H et al.: A dose escalation study designed to demonstrate the safety, tolerability, and efficacy of the fully human anti-TNF antibody, D2E7, given in combination with methotrexate (MTX) in patients with active RA. Arthritis Rheum. (2000) 43:S391.
82. ALETAHA D, SMOLEN JS: The rheumatoid arthritis patient in the clinic comparing more than 1300 consecutive DMARD courses. Rheumatology (2002) 41:1367-1374.
83. 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. Arthritis Rheum. (1999) 42(Suppl.):S400.
84. KEYSTONE E, KAVANAUGH AF, SHARP J et al.: Adalimumab (D2E7), a fully human anti-TNF-alpha monoclonal antibody, inhibits the progression of structural joint damage in patients with active RA despite concomitant methotrexate therapy. Arthritis Rheum. (2002) 46:S205.
85. TEMEKONIDIS TI, GEORGIADIS AN, ALAMANOS Y, BOUGIAS DV, VOULGARI PV, DROSOS AA: Infliximab treatment in combination with cyclosporin A in patients with severe refractory rheumatoid arthritis. Ann. Rheum. Dis. (2002) 61:822-825.
86. OCHSENKUHN T, GOKE B, SACKMANN M: Combining infliximab with 6-mercaptopurine/azathioprine for fistula therapy in Crohn's disease. Am. J. Gastroenterol. (2002) 97:2022-2025.
87. FURST DE, FLEISCHMANN R, BIRBARA C et al.: Efficacy of adalimumab (D2E7), a fully human anti-TNF monoclonal antibody, administered to rheumatoid arthritis patients in combination with other antirheumatic therapy in the STAR (safety trial of adalimumab in rheumatoid arthritis) trial. Ann. Rheum. Dis. (2002) 61(Suppl. 1):174.
88. SCHIFF M, FURST DE, STRAND V et al.: A randomized, controlled, safety trial of adalimumab (D2E7), a fully human anti-TNF monoclonal antibody, given to RA patients in combination with standard rheumatologic care: the STAR (safety trial of adalimumab in rheumatoid arthritis) trial. Ann. Rheum. Dis. (2002) 61(Suppl. 1):169.
89. KALDEN JR: Expanding role of biologic agents in rheumatoid arthritis. J. Rheumatol. Suppl. (2002) 66:27-37.
90. CHOY EH, HAZLEMAN B, SMITH M et al.: Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a Phase II double-blind, randomized, dose-escalating trial. Rheumatology (2002) 41(10):1133-1137.
91. DAVIS MW, FEIGE U, BENDELE AM, MARTIN SW, EDWARDS CK 3RD: Treatment of rheumatoid arthritis with PEGylated recombinant human soluble tumour necrosis factor receptor type I: a clinical update. Ann. Rheum Dis. (2000) 59(Suppl. 1):i41-i43.