Monoclonal antibodies in rheumatoid arthritis

A large munber of mAbs targeting different mediators have been tested in RA. They inhibit either C3dokines, adhesion molecules, MHC, or T cells. 

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Choy EH, Panayi GS, Emery P, Madden S, Breedveld EC, Kraan MC, Kalden JR, Rascu A, Brown JC, Rapson N, Johnston JM. Repeat-cycle study of high-dose intravenous 4162W94 anti-CD4 humanized monoclonal antibody in rheumatoid arthritis. A randomized placebo-controUed trial. Rheumatology (Oxford) 2002 41(10) 1142-8. 

Ng C M, Bruno R, Combs D, et al. (2005). Population pharmacokinetics of rituximab (anti-CD20 monoclonal antibody) in rheumatoid arthritis patients during a phase II clinical trial. Clin. Pharmacol. 45 792-801. 

Paleolog, E. W., Hunt, M., Elliott, M., Feldmann, M., Maini, R. N., and Woody, J. (1996). Deactivation of vascular endothelium by monoclonal anti tumor necrosis factor a antibody in rheumatoid arthritis. Arthritis Rheum. 39, 1082-1091. 

Haringman JJ, Gerlag DM, Smeets TJ, et al. A randomized placebo controlled trial with an anti-MCP-1 (CCL2) monoclonal antibody in patients with rheumatoid arthritis [Abstract 519], Arthritis Rheum 2004 50(Suppl) S238. 

Maini, R. N., Breedveld, E. C., Kalden, J. R., et al. (1998) Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis and Rheumatism. 41, 1552-1563. 

Keystone, E. C., Kavanaugh, A. E., Sharp, J. T., et al. (2004) Radiographic, cUnical, and functional outcomes of treatment with adaUmumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy a randomized, placebo-controUed, 52-week trial. Arthritis and Rheumatism. 50, 1400-1411. 

Mecfianism of Action A monoclonal antibody that binds specifically to tumor necrosis factor (TNF) alpha, blocking its interaction with cell surface TNF receptors, Tfier-apeutic Effect Reduces inflammation, tenderness, and swelling of joints slows or prevents progressive destruction of joints in rheumatoid arthritis. 

Maini, R., St. Clair, E. W., Breedveld, F., Furst, D., Kalden, J., Weisman, M., Smolen, J., Emery, P. 1999. Infliximab (chimeric anti-tumor necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate a randomised phase HI trial. Attract study group. Lancet 354 1932-1939. 

Weinblatt, M. E., Maddison, P. J., Bulpitt, K. J. el al. (1995). GAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intravenous dose-escalation study. Arthritis Rheum. 38, 1589-1594. 

Choy EH, Connolly DJ, Rapson N, Jeal S, Brown JC, Kingsley GH, Panayi GS, Johnston JM. Pharmacokinetic, pharmacodynamic and clinical effects of a humanized IgGl anti-CD4 monoclonal antibody in the peripheral blood and synovial fluid of rheumatoid arthritis patients. Rheumatology (Oxford) 2000 39(10) 1139-46. 

Charles PJ, Smeenk RJ, De Jong J, Feldmaim M, Maini RN. Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha findings in open-label and randomized placebo-controlled trials. Arthritis Rheum 2000 43(11) 2383-90. 

Rankin ECC, Isenberg DA. Monoclonal antibody therapy in rheumatoid arthritis. An update on recent progress. Clin Immunother 1996 6 143-53. 

Answer C. Interferon-gamma lb (recombinant form) is used in chronic granulomatous disease to decrease infection liability because it increases the formation of tumor necrosis factor (TNF). Infliximab is a monoclonal antibody to TNF used in rheumatoid arthritis, and its use may lead to an increased infection rate. Aldesleukin is a recombinant form of IL-2. 

Adalimimab (Humira) is another anti-TNF product for intravenous use. This recombinant human IgGj monoclonal antibody was created by phage display technology and is approved for use in rheumatoid arthritis. 

Elliott M J, Maini R N, Feldmann M, et al. (1994). Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 344 1105-1110. 

Weisman M FI, Moreland L W, Furst D E, et al. (2003). Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate A pilot study. Clin. Therapeut. 25 1700-1721. 

T. J., Baeten, D., van den Bosch, E., Bresnihan, B., Breedveld, E.C., Dinant, H.J., Legay, F., Gram, H., Loetscher, P., Schmouder, R., Woodworth, T, and Tak, P.P. (2006) A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis. Arthritis and Rheumatism, 54, 2387-2392. 

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