Biological therapies for rheumatoid arthritis: Progress to date

BioDrugs

Volumn 27, Issue 4, 2013, Pages 329-345

  Malviya, Gaurav ^a,b   Salemi, Simonetta ^c   Laganà, Bruno ^c   Diamanti, Andrea Picchianti ^c   D'Amelio, Raffaele ^c   Signore, Alberto ^a,b  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ABATACEPT; ADALIMUMAB; CERTOLIZUMAB PEGOL; CYCLOPHOSPHAMIDE; ETANERCEPT; GOLIMUMAB; HYBRID PROTEIN; INFLIXIMAB; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; METHOTREXATE; MONOCLONAL ANTIBODY; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RITUXIMAB; TOCILIZUMAB;

ABDOMINAL PAIN; ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS; ALLERGIC REACTION; ANEMIA; ARTHRALGIA; ASTHENIA; BACTERIAL INFECTION; BIOLOGICAL THERAPY; BONE INFECTION; BRONCHITIS; BRONCHOSPASM; CELLULITIS; CONJUNCTIVITIS; COUGHING; DIARRHEA; DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERANCE; DYSPNEA; ECCHYMOSIS; ERYTHEMA; FEVER; FLUSHING; HEADACHE; HUMAN; HYPERLIPIDEMIA; HYPERSENSITIVITY; HYPERTENSION; INFECTION; INFECTIOUS ARTHRITIS; INFLAMMATION; INJECTION SITE PAIN; INJECTION SITE REACTION; LEUKOPENIA; LOWER RESPIRATORY TRACT INFECTION; MYALGIA; NAUSEA; PAIN; PNEUMONIA; PRIORITY JOURNAL; PRURITUS; RASH; RESPIRATORY TRACT INFECTION; REVIEW; RHEUMATOID ARTHRITIS; RHINOPHARYNGITIS; SIDE EFFECT; SINUSITIS; SKIN INFECTION; SORE THROAT; TUBERCULOSIS; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; URTICARIA; VERTIGO; VIRUS INFECTION; VOMITING;

EID: 84880790447     PISSN: 11738804     EISSN: 1179190X     Source Type: Journal    
DOI: 10.1007/s40259-013-0021-x     Document Type: Review

References (161)

1. Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002;46:2287-93.
2. Baecklund E, Ekbom A, Sparen P, Feltelius N, Klareskog L. Disease activity and risk of lymphoma in patients with rheumatoid arthritis: nested case-control study. BMJ. 1998;317:180-1.
3. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003;107:1303-7.
4. Wolfe F, Freundlich B, Straus WL. Increase in cardiovascular disease prevalence in rheumatoid arthritis. J Rheumatol. 2003;30:36-40.
5. Thomas E, Brewster DH, Black RJ, Macfarlane GJ. Risk of malignancy among patients with rheumatic conditions. Int J Cancer. 2000;88:497-502.
6. Ortega-Hernández OD, Pineda-Tamayo R, Pardo AL, Rojas-Villaraga A, Anaya JM. Cardiovascular disease is associated with extra-articular manifestations in patients with rheumatoid arthritis. Clin Rheumatol. 2009;28:767-75.
7. Anaya JM, Correa PA, Mantilla RD, Arcos-Burgos M. Rheumatoid arthritis association in Colombian population is restricted to HLA-DRB1*04 QRRAA alleles. Genes Immun. 2002;3:56-68.
8. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37:481-94.
9. Young A, Koduri G, Batley M, Kulinskaya E, Gough A, Norton S, et al. Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischemic heart disease and in pulmonary fibrosis. Rheumatology. 2007;46:350-7.
10. Gabriel SE, Crowson CS, Kremers HM, Doran MF, Turesson C, O'Fallon WM, et al. Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum. 2003;48:54-8.
11. O'Dell JR, Haire CE, Erickson N, Drymalski W, Palmer W, Eckhoff PJ, et al. Treatment of rheumatoid arthritis with methotrexate, sulphasalazine and hydroxychloroquine, or a combination of these medications. New Engl J Med. 1996;334:1287-91.
12. Landewè RB, Boers M, Verhoeven AC, Westhovens R, van de Laar MA, Markusse HM, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. 2002;46:347-56.
13. Rantalaiho V, Korpela M, Laasonen L, Kautiainen H, Järvenpä ä S, Hannonen P, et al. Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial. Arthritis Res Ther. 2010;12:R122.
14. Choy EHS, Kingsley GH, Panayi GS. Monoclonal antibody therapy in rheumatoid arthritis. Br J Rheumatol. 1998;37:484-90.
15. Fan PT, Leong KH. The use of biological agents in the treatment of rheumatoid arthritis. Ann Acad Med Singapore. 2007;36:128-34.
16. Malviya G, Galli F, Sonni I, Pacilio M, Signore A. Targeting T and B lymphocytes with radiolabelled antibodies for diagnostic and therapeutic applications. Q J Nucl Med Mol Imaging. 2010;54:654-76.
17. Kindt TJ, Goldsby RA, Osborne BA. Kuby immunology. 6th ed. New York: Freeman; 2007.
18. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495-7.
19. Brekke OH, Sandlie I. Therapeutic antibodies for human diseases at the dawn of the twenty-first century. Nat Rev Drug Discov. 2003;2:52-62.
20. Aksentijevich I, Flinn IW. Monoclonal antibody therapy with autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Cancer Control. 2002;9:99-105.
21. Morrison SL, Johnson MJ, Herzenberg LA, Oi VT. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci. 1984;81:6851-5.
22. Hanauer SB. Safety of infliximab in clinical trials. Aliment Pharmacol Ther. 1999;13:16-22.
23. Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature. 1986;321:522-5.
24. Holmes MA, Buss TN, Foote J. Conformational correction mechanisms aiding antigen recognition by a humanized antibody. J Exp Med. 1998;187:479-85.
25. Rajagopalan K, Pavlinkova G, Levy S, Pokkuluri PR, Schiffer M, Haley BE, et al. Novel unconventional binding site in the variable region of immunoglobulins. Proc Natl Acad Sci. 1996;93:6019-24.
26. Hoogenboom HR. Selecting and screening recombinant antibody libraries. Nat Biotechnol. 2005;23:1105-16.
27. Lonberg N. Human antibodies from transgenic animals. Nat Biotechnol. 2005;23:1117-25.
28. Trikha M, Yan L, Nakada MT. Monoclonal antibodies as therapeutics in oncology. Curr Opin Biotechnol. 2002;13:609-14.
29. Sidhu S. Phage display in pharmaceutical biotechnology. Curr Opinion Biotechnol. 2000;11:610-6.
30. Kay BK, Kurakin AV, Hyde-De Ruyscher R. From peptides to drugs via phage display. Drug Discov Today. 1998;3:370-8.
31. Bain B, Brazil M. Adalimumab. Nat Rev Drug Discov. 2003;2:693-4.
32. Weir AN, Nesbitt A, Chapman AP, Popplewell AG, Antoniw P, Lawson AD. Formatting antibody fragments to mediate specific therapeutic functions. Biochem Soc Trans. 2002;30:512-6.
33. Kaushik VV, Moots RJ. CDP-870 (certolizumab) in rheumatoid arthritis. Expert Opin Biol Ther. 2005;5:601-6.
34. Knight DM, Trinh H, Le J, Siegel S, Shealy D, McDonough M, et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol. 1993;30:1443-53.
35. Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J. Chimeric anti-TNFα monoclonal antibody cA2 binds recombinant transmembrane TNFα and activates immune effector functions. Cytokine. 1995;7:251-9.
36. Remicade® (infliximab) package insert. Malvern, Pennsylvania: Centocor; revised Apr 2007.
37. ten Hove T, van Montfrans C, Peppelenbosch MP, van Deventer SJ. Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease. Gut. 2002;50:206-11.
38. Siegel SA, Shealy DJ, Nakada MT, Le J, Woulfe DS, Probert L, et al. The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo. Cytokine. 1995;7:15-25.
39. Barone D, Krantz C, Lambert D, Maggiora K, Mohler K. Comparative analysis of the ability of etanercept and infliximab to lyse TNF-expressing cells in a complement dependent fashion. Arthritis Rheum. 1999;42:S90.
40. Verstappen SM, King Y, Watson KD, Symmons DP, Hyrich KL, BSRBR Control Centre Consortium, BSR Biologics Register. Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2011;70(5):823-6.
41. Gardam MA, Keystone EC, Menzies R, Manners S, Skamene E, Long R, et al. Anti-tumor necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis. 2003;3:148-55.
42. EMEA. European Public Assessment Report (EPAR) on Remicade. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Summary-for-the- public/human/000240/WC500050883.pdf. Accessed 22 Feb 2013.
43. Baert F, Noman M, Vermeire S, Van Assche G, D'Haens G, Carbonez A, et al. Influence of immunogenicity on the longterm efficacy of infliximab in Crohn's disease. N Engl J Med. 2003;348:601-8.
44. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359:1541-9.
45. Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology. 2003;124:917-24.
46. Lipsky PE, van der Heijde DM, St. Clair EW, Furst DE, Breedveld FC, Kalden JR, et al; for the Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 2000;343:1594-602.
47. St. Clair EW, van Der Heijde DM, Smolen JS. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis. Arthritis Rheum. 2004;50:3432-43.
48. Westhovens R, Yocum D, Han J, Berman A, Strusberg I, Geusens P, Rahman MU, START Study Group. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial. Arthritis Rheum. 2006;54:1075-86.
49. Smolen JS, Han C, Bala M, Maini RN, Kalden JR, van der Heijde D, Breedveld FC, Furst DE, Lipsky PE. Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement. Arthritis Rheum. 2005;52:1020-30.
50. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381-90.
51. Paul J, Anderson PJ. Tumor necrosis factor inhibitors: clinical implications of their different immunogenicity profiles. Semin Arthritis Rheum. 2005;34(Suppl):19-22.
52. Rau R. Adalimumab (a fully human anti-tumour necrosis factor a monoclonal antibody) in the treatment of active rheumatoid arthritis: the initial results of five trials. Ann Rheum Dis. 2002;61(Suppl II):70-3.
53. Adalimumab (Humira). European Public Assessment Report: scientific discussion. http://www.emea.europa.eu/docs/en-GB/document-library/EPAR- Scientific-Discussion-Variation/human/000481/WC500050878.pdf. Accessed 16 Mar 2011.
54. Humira® (adalimumab) package insert. Abbott Park, Illinois: Abbott Laboratories; revised Feb 2007.
55. Keystone E, Haraoui B. Adalimumab therapy in rheumatoid arthritis. Rheum Dis Clin N Am. 2004;30:349-64.
56. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, 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.
57. Weinblatt ME, Keystone EC, Furst DE, Kavanaugh AF, Chartash EK, Segurado OG. Long-term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4-year extended study. Ann Rheum Dis. 2006;65:753-9.
58. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen S, Pavelka K, van Vollenhoven R, et al. The PREMIER study a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54:26-37.
59. Burmester GR, Mariette X, Montecucco C, Monteagudo-Sàez I, Malaise M, Tzioufas AG, et al. Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis: the Research in Active Reumatoid Arthritis (ReAct) trial. Ann Rheum Dis. 2007;66:732-9.
60. Rituxan® (Rituximab), package insert. Genentech, San Francisco, CA; revised 21 Feb 2007.
61. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435-45.
62. Stashenko P, Nadler LM, Hardy R, Schlossman SF. Characterization of a human B lymphocyte-specific antigen. J Immunol. 1980;125:1678-85.
63. Tedder TF, Boyd AW, Freedman AS, Nadler LM, Schlossman SF. The B cell surface molecule B1 is functionally linked with B-cell activation and differentiation. J Immunol. 1985;135:973-9.
64. Dorner T, Rumester G. The role of B-cells in rheumatoid arthritis: mechanisms and therapeutic targets. Curr Op Rheum. 2003;15:246-52.
65. Stern M, Herrmann R. Overview of monoclonal antibodies in cancer therapy: present and promise. Crit Rev Oncol Hematol. 2005;54:11-29.
66. Johnson PW, Glennie MJ. Rituximab: mechanisms and applications. Br J Cancer. 2001;85:1619-23.
67. Olszewski AJ, Grossbard ML. Empowering targeted therapy: lessons from rituximab. Sci STKE. 2004;2004(241):30. doi: 10.1126/stke.2412004pe30.
68. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350:2572-81.
69. Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54:2793-806.
70. Sato K, Tsuchiya M, Saldanha J, Koishihara Y, Ohsugi Y, Kishimoto T, et al. Reshaping a human antibody to inhibit the interleukin 6 dependent tumor cell growth. Cancer Res. 1993;53:851-6.
71. Mihara M, Kasutani K, Okazaki M, Nakamura A, Kawai S, Sugimoto M, et al. Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family. Int Immunopharmacol. 2005;5:1731-40.
72. Kishimoto T. Interleukin-6: from basic science to medicine - 40 years in immunology. Annu Rev Immunol. 2005;23:1-21.
73. Keizer RJ, Huitema AD, Schellens JH, Beijnen JH. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49:493-7.
74. RoActemra (tocilizumab). European Medicines Agency. http://www.ema. europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000955/ human-med-001042.jsp&mid=WC0b01ac058001d125&murl=menus/medicines/ medicines.jsp&jsenabled=true. Accessed 22 Feb 2013.
75. Köller MD. Targeted therapy in rheumatoid arthritis. Wien Med Wochenschr. 2006;156:53-60.
76. Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiological benefit from x ray reader-blind randomized controlled trial of tocilizumab. Ann Rheum Dis. 2007;66:1162-7.
77. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Rieke Alten R, for the OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371:987-97.
78. Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, Woodworth T, Gomez-Reino JJ. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008;58:2968-80.
79. Kremer J, Fleischmann R, Brzezicki J, Ambs P, Alecock E, Burgos-Vargas R, Halland A. Tocilizumab inhibits structural joint damage, improves physical function, and increases DAS28 remission rates in RA patients who respond inadequately to methotrexate: The LITHE Study. Oral presentation at EULAR 2009, 10-13 June.
80. Hirohata S. Fully human anti TNF-alpha monoclonal antibodies (adalimumab, golimumab). Nippon Rinsho. 2007;65:1202-28.
81. SIMPONI™ (golimumab) [prescribing information]. Malvern: Centocor Ortho Biotech.
82. Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, et al. Golimumab, a human antibody to tumour necrosis factor α given by monthly sub cutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis. 2009;68:789-96.
83. Smolen JS, Kay J, Doyle MK, Landewé R, Matteson EL, Wollenhaupt J, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor a inhibitors (GO-AFTER study): a multicentre, randomised, doubleblind, placebo-controlled phase III trial. Lancet. 2009;374:210-21.
84. Emery P, Fleischmann RM, Moreland LW, Hsia EC, Strusberg I, Durez P, et al. Golimumab, a new human anti-tumor necrosis factor-α monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naïve patients with active rheumatoid arthritis. Arthritis Rheumatol. 2009;60:2272-83.
85. Winter TA, Wright J, Ghosh S, Jahnsen J, Innes A, Round P. Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study. Aliment Pharmacol Ther. 2004;20:1337-46.
86. Schreiber S, Rutgeerts P, Fedorak RN, Kareemi MK, Kamm MA, Boivin M, et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology. 2005;129:807-18.
87. Nesbitt AM, Henry AJ. High affinity and potency of the pegylated Fab' fragment CDP870 - a direct comparison with other anti-TNF agents. Am J Gastroenterol. 2004;99:S253.
88. Fossati G, Nesbitt A. In vitro complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by the anti-TNF agents adalimumab, etanercept, infliximab and certolizumab pegol (CDP870). Am J Gastroenterol. 2005;100(Suppl):S299.
89. Fossati G, Nesbitt A. Effect of the anti-TNF agents, adalimumab, etanercept, infliximab, and certolizumab pegol (CDP870) on the induction of apoptosis in activated peripheral blood lymphocytes and monocytes. Am J Gastroenterol. 2005;100:S298-9.
90. Nesbitt AM, Gramlick A, Fossati G. Neutralization of soluble and membrane tumor necrosis factor-α (TNF-α) by infliximab, adalimumab or certolizumab pegol using p55 or p75 TNF-α receptor-specific bioassays. Gastroenterology. 2006;130:A-697. [Abstract W1634].
91. Fleischmann R, Vencovsky J, van Vollenhoven RF, Borenstein D, Box J, et al. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis. 2009;68:805-11.
92. Smolen J, Landewé RB, Mease P, Brzezicki J, Mason D, Luijtens K, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis. 2009;68:797-804.
93. Keystone E, van der Heijde D, Mason D, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2008;58:3319-29.
94. Ikonomidis I, Lekakis JP, Nikolaou M, Paraskevaidis I, Andreadou I, Kaplanoglou T, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation. 2008;117:2662-9.
95. Le Loet X, Nordstrom D, Rodriguez M, Rubbert A, Sarzi-Puttini P, Wouters JM, et al. Effect of anakinra on functional status in patients with active rheumatoid arthritis receiving concomitant therapy with traditional disease modifying antirheumatic drugs: evidence from the OMEGA trial. J Rheumatol. 2008;35:1538-44.
96. Mertens M, Singh JA. Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol. 2009;36:1118-25.
97. Moreland L, Bate G, Kirkpatrick P. Abatacept. Nat Rev Drug Discov. 2006;5:185-6.
98. Todd DJ, Costenbader KH, Weinblatt ME. Abatacept in the treatment of rheumatoid arthritis. Int J Clin Pract. 2007;61(3):494-500.
99. Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov. 2003;2:473-88.
100. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991;174:561-9.
101. Linsley PS, Wallace PM, Johnson J, Gibson MG, Greene JL, Ledbetter JA, et al. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science. 1992;257:792-5.
102. FDA labelling information. http://www.fda.gov/ohrms/dockets/ac/05/ briefing/2005-4170B1-02-01-FDA-Abatacept.pdf. Accessed 22 Feb 2013.
103. Reiser H, Stadecker MJ. Costimulatory B7 molecules in the pathogenesis of infectious and autoimmune diseases. N Engl J Med. 1996;335:1369-77.
104. Nogid A, David Q. Role of abatacept in the management of rheumatoid arthritis. Clin Therap. 2006;28:11.
105. Orencia® (abatacept), package insert. Bristol-Myers Squibb, Princeton, NJ, USA; revised Mar 2007.
106. Emery P, Kosinski M, Li T, Martin M, Williams GR, Becker JC, et al. Treatment of rheumatoid arthritis patients with abatacept and methotrexate significantly improved health-related quality of life. J Rheumatol. 2006;33:681-9.
107. Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: a one-year randomized, placebo-controlled study. Arthritis Rheum. 2006;54:2807-16.
108. Gatto B. Biologics targeted at TNF: design, production and challenges. Reumatismo. 2006;58:94-103.
109. Feldmann M, Maini RN. Anti-TNF-α therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol. 2001;19:163-96.
110. Enbrel® (etanercept) package insert. Thousand Oaks, CA: Immunex; issued 1 Dec 2006.
111. Keystone E, Schiff M, Kremer JM, Kafka S, Lovy M, DeVries T, et al. Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: results of a multicentre, randomized, double blind placebo controlled trial. Arthritis Rheum. 2004;50:353-63.
112. Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-93.
113. Nanda S, Bathon JM. Etanercept: a clinical review of current and emerging indications. Expert Opin Pharmacother. 2004;5:1175-86.
114. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, 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.
115. Foerder C, Rogge M. Immunogenicity of Enbrel®: clinical trial observations. Annual European Congress of Rheumatology 2002.
116. Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002;46:1443-50.
117. van der Heijde D, Klareskog L, Rodriguez-Valverde V, Codreanu C, Bolosiu H, Melo-Gomes J, Tornero-Molina J, Wajdula J, Pedersen R, Fatenejad S. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum. 2006;54:1063-74.
118. Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-82.
119. Ding C, Jones G. Belimumab Human Genome Sciences/Cambridge Antibody Technology/GlaxoSmithKline. Curr Opin Investig Drug. 2006;7:464-72.
120. Baker KP, Edwards BM, Main SH, Choi GH, Wager RE, Halpern WG, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. 2003;48:3253-65.
121. Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999;189:1747-56.
122. Huard B, Schneider P, Mauri D, Tschopp J, French LE. T cell costimulation by the TNF ligand BAFF. J Immunol. 2001;167:6225-31.
123. Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285:260-3.
124. Moreland LW. Biologic therapies on the horizon for rheumatoid arthritis. J Clin Rheumatol. 2004;10:S32-9.
125. Parry TJ, Riccobene TA, Strawn SJ, Williams R, Daoud R, Carrell J, et al. Pharmacokinetics and immunological effects of exogenously administered recombinant human B lymphocyte stimulator (BLyS) in mice. J Pharmacol Exp Ther. 2001;296:396-404.
126. Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001;44:1313-9.
127. Tan SM, Xu D, Roschke V, Perry JW, Arkfeld DG, Ehresmann GR, et al. Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis. Arthritis Rheum. 2003;48:982-92.
128. Jin X, Ding C. Belimumab - an anti-BLyS human monoclonal antibody for rheumatoid arthritis. Expert Opin Biol Ther. 2013;13:315-22.
129. McInnes IB, al-Mughales J, Field M, Leung BP, Huang FP, Dixon R, et al. The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis. Nat Med. 1996;2:175-82.
130. McInnes IB, Leung BP, Sturrock RD, Field M, Liew FY. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. Nat Med. 1997;3:189-95.
131. Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103:1345-52.
132. Waldmann TA. Targeting the interleukin-15 system in rheumatoid arthritis. Arthritis Rheum. 2005;52:2585-8.
133. McInnes I, Martin R, Zimmerman-Gorska I, Nayiager, Sun, Patel, Appleton. Safety and efficacy of a human monoclonal antibody to IL-15 (AMG 714) in patients with rheumatoid arthritis (RA): results from a multicenter, randomized, double-blind, placebo-controlled trial. American College of Rheumatology National Scientific meetings 2004. [Abstract 527].
134. Baslund B, Tvede N, Danneskiold-Samsoe B, Larsson P, Panayi G, Petersen J, et al. Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum. 2005;52:2686-92.
135. Vugmeyster Y, Beyer J, Howell K, Combs D, Fielder P, Yang J, Qureshi F, Sandlund B, Kawaguchi L, Dummer W, Lowman H, McKeever K. Depletion of B cells by a humanized anti-CD20 antibody PRO70769 in Macaca fascicularis. J Immunother. 2005;28:212-9.
136. Genovese MC, Kaine JL, Lowenstein MB, Del Giudice J, Baldassare A, Schechtman J, et al. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008;58:2652-61.
137. Haringman JJ, Oostendorp RL, Tak PP. Targeting cellular adhesion molecules, chemokines and chemokine receptors in rheumatoid arthritis. Expert Opin Emerg Drugs. 2005;10:299-310.
138. Koch AE. Chemokines and their receptors in rheumatoid arthritis: future targets? Arthritis Rheum. 2005;52:710-21.
139. Haringman JJ, Gerlag DM, Smeets TJM, Baeten D, Bosch FV, Bresnihan B, et al. A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:2387-92.
140. Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997;390:175-9.
141. Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol. 2002;22:549-53.
142. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, et al. A single-dose placebo controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19:1059-66.
143. Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, et al.
144. Geusens P. The role of RANK ligand/osteoprotegerin in rheumatoid arthritis. Ther Adv Musculoskel Dis. 2012;4:225-33.
145. A randomized, double-blind, placebo-controlled, multiple dose study to evaluate the efficacy, safety, and pharmacokinetics of subcutaneous AMG 108 in subjects with rheumatoid arthritis. http://clinicaltrials.gov/ct/show/ NCT00293826. Accessed 22 Feb 2013.
146. Ostergaard M, Wiell C, Dawes PT, Rigby W, Petersen J, Kastberg H, et al. First clinical results of HuMax-CD20 fully human monoclonal IgG1 antibody treatment in rheumatoid arthritis. The Johns Hopkins Arthritis Centre, Highlights from the annual European congress of rheumatology 2006.
147. Hagenbeek A, Plesner T, Johnson P, Pedersen LM, Walewski J, Hellmann A, et al. HuMax-CD20 fully human monoclonal antibody in follicular lymphoma. First human exposure: early results of an ongoing phase I/II trial. ASH 46th Annual Meeting 2004.
148. Pawluczkowycz AW, Beurskens FJ, Beum PV, et al. Binding of submaximal C1q promotes complement-dependent cytotoxicity (CDC) of B cells opsonized with anti-CD20 mAbs ofatumumab (OFA) or rituximab (RTX): considerably higher levels of CDC are induced by OFA than by RTX. J. Immunol. 2009;183:749-58.
149. Palladino MA, Bahjat FR, Theodorakis EA, Moldawer LL. Anti-TNF-α therapies: the next generation. Nature. 2003;2:736-46.
150. Genovese MC. Biologic therapies in clinical development for the treatment of rheumatoid arthritis. J Clin Rheumatol. 2005;11:S45-54.
151. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-24.
152. 99mTc-infliximab. Arthritis Rheum. 2005;52:1224-6.
153. Barrera P, Oyen WJ, Boerman OC, van Riel PL. Scintigraphic detection of tumour necrosis factor in patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62:825-8.
154. 99mTechnetium labelled anti-TNF-α antibodies for the therapy decision making and follow-up of patients with rheumatoid arthritis. Q J Nucl Med Mol Imaging. 2008;52(Suppl 1):13-4.
155. Malviya G, Laganà B, Milanetti F, Del Mastro C, Familiari D, Dierckx RA, Scopinaro F, D'Amelio R, Signore A. Use of 99m-technetium labelled rituximab for imaging of patients with chronic inflammatory diseases. Eur J Nucl Med Mol Imaging. 2008;35(Suppl 2):S142.
156. 99mTc-anti- CD3. Brit J Radiol. 2008;81:25-9.
157. Malviya G, Conti F, Chianelli M, Scopinaro F, Dierckx RA, Signore A. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies. Eur J Nucl Med Mol Imaging. 2010;37:386-98.
158. Malviya G, de Vries EF, Dierckx RA, Signore A. Synthesis and evaluation of (99m)Tc-labelled monoclonal antibody 1D09C3 for molecular imaging of major histocompatibility complex class II protein expression. Mol Imaging Biol. 2011;13:930-39. doi: 10.1007/s11307-010-0407-9.
159. Malviya G, D'Alessandria C, Bonanno E, Vexler V, Massari R, Trotta C, Scopinaro F, Dierckx R, Signore A. Radiolabeled humanized anti-CD3 monoclonal antibody visilizumab for imaging human T-lymphocytes. J Nucl Med. 2009;50:1683-91.
160. Goldsmith SJ, Signore A. An overview of the diagnostic and therapeutic use of monoclonal antibodies in medicine. Q J Nucl Med Mol Imaging. 2010;54:574-81.
161. Signore A, Mather SJ, Piaggio G, Malviya G, Dierckx RA. Molecular imaging of inflammation/infection: nuclear medicine and optical imaging agents and methods. Chem Rev. 2010;110:3112-45.