Antibodies to Tumor Necrosis Factors in the Treatment of Rheumatoid Arthritis and Spondyloarthritis: The Basic Science, Clinical Science and Unmet Needs; Results from a Single Center

Sundeep Kumar Upadhyaya

Indraprastha-Apollo Hospitals (IAH), New Delhi, India.

DOI: 10.4236/ojra.2014.42013                

Abstract

Inflammatory rheumatological diseases like rheumatoid arthritis (RA) and ankylosing spondylitis/Spondyloarthritis (AS/SpA), have been treated with NSAIDs (non steroidal anti-inflammatory drugs), corticosteroids, and DMARDs (disease modifying anti-rheumatic drugs).These have been only partially effective for the management of symptoms, since they are rarely associated with the complete control of disease and rarely slow down radiological damage. Several cytokines have been implicated in the pathogenesis of the inflammation and tumor necrosis factor (TNF) is the most important. The last decade and a half has seen advances in the form of “anti-TNF” therapies for RA and AS/SpA patients which target and neutralize the TNF cytokines, and thus reduce the disease activity. Two anti-TNF therapies have been used in India for treating DMARD resistant RA and AS/SpA for the last 13 years; Infliximab and Etanercept respectively. This paper is a description of the clinical outcomes and unmet needs/toxicities associated with the treatment of RA and AS/SpA with anti-TNF therapies (Infliximab, Etanercept), at a single rheumatology center (tertiary care, super-specialty hospital, Indraprastha Apollo Hospitals, New Delhi) in north India.

Keywords

Anti-TNF Antibodies, Biologic Agents, Rheumatoid Arthritis, Ankylosing Spondylitis, Biologic Treatment, Spondyloarthritis, Infliximab, Etanercept, DMARD

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Maini, R., St. Clair, E.W., Breedveld, F., et al. (1999) Infliximab (Chimeric Anti-Tumour Necrosis Factor α Monoclonal Antibody) versus Placebo in Rheumatoid Arthritis Patients Receiving Concomitant Methotrexate: A Randomized Phase III Trial. Lancet, 354, 1932-1939. http://dx.doi.org/10.1016/S0140-6736(99)05246-0
[2]	Lipsky, P.E., Desiree, M.F.M., van der Heijde, D.M., et al. (2000) Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis. The New England Journal of Medicine, 343, 1594-1602. http://dx.doi.org/10.1056/NEJM200011303432202
[3]	St. Clair, E.W., van der Heijde, D.M., Smolen, J.S., et al. (2004) Combination of Infliximab and Methotrexate Therapy for Early Rheumatoid Arthritis: A Randomized, Controlled Trial. Arthritis & Rheumatology, 50, 3432-3443. http://dx.doi.org/10.1002/art.20568
[4]	Braun, J., Brandt, J., Listing, J., et al. (2002) Treatment of Active Ankylosing Spondylitis with Infliximab: A Randomised Controlled Multicentre Trial. Lancet, 359, 1187-1193. http://dx.doi.org/10.1016/S0140-6736(02)08215-6
[5]	Braun, J., Baraliakos, X., Brandt, J., et al. (2005) Persistent Clinical Response to the Anti-TNF-α Antibody Infliximab in Patients with Ankylosing Spondylitis over 3 Years. Rheumatology, 44, 670-676. http://dx.doi.org/10.1093/rheumatology/keh584
[6]	Moreland, L.W., Schiff, M.H., Baumgartner, S.W., et al. (1999) Etanercept Therapy in Rheumatoid Arthritis: A Randomized, Controlled Trial. Annals of Internal Medicine, 130, 478-486. http://dx.doi.org/10.7326/0003-4819-130-6-199903160-00004
[7]	Weinblatt, M.E., Kremer, K.M., Bankhurst, A.D., et al. (1999) A Trial of Etanercept, a Recombinant Tumor Necrosis Factor Receptor: Fc Fusion Protein in Patients with Rheumatoid Arthritis Receiving Methotrexate. The New England Journal of Medicine, 340, 253-259. http://dx.doi.org/10.1056/NEJM199901283400401
[8]	Moreland, L.M., Cohen, S.B., Baumgartner, S.W., et al. (2001) Long-Term Safety and Efficacy of Etanercept in Patients with Rheumatoid Arthritis. The Journal of Rheumatology, 28, 1238-1244.
[9]	Davis, J.C., Van der Heijde, D., Braun, J., et al. (2003) Recombinant Human Tumor Necrosis Factor Receptor (Etanercept) for Treating Ankylosing Spondylitis: A Randomized, Controlled Trial. Arthritis & Rheumatology, 48, 3230-3236. http://dx.doi.org/10.1002/art.11325
[10]	Davis, J.C., van der Heijde, D., Braun, J., et al. (2005) Sustained Durability and Tolerability of Etanercept in Ankylosing Spondylitis for 96 Weeks. Annals of the Rheumatic Diseases, 64, 1557-1562. http://dx.doi.org/10.1136/ard.2004.035105
[11]	Brandt, J., Khariouzov, A., Listing, J., et al. (2003) Six-Month Results of a Double-Blind, Placebo-Controlled Trial of Etanercept Treatment in Patients with Active Ankylosing Spondylitis. Arthritis & Rheumatology, 48, 1667-1675. http://dx.doi.org/10.1002/art.11017
[12]	Baraliakos, X., Listing, J., Brandt, J., et al. (2005) Clinical Response to Discontinuation of Anti-TNF Therapy in Patients with Ankylosing Spondylitis after 3 Years of Continuous Treatment with Infliximab. Arthritis Research & Therapy, 7, R439-R444. http://dx.doi.org/10.1186/ar1693
[13]	Koch, A.E., Kunkel, S.L. and Strieter, R.M. (1995) Cytokines in Rheumatoid Arthritis. Journal of Investigative Medicine, 43, 28-38.
[14]	Feldman, M., Brennan, F.M. and Maini, R.N. (1996) Role of Cytokines in Rheumatoid Arthritis. Annual Review of Immunology, 43, 28-38.
[15]	Bazzoni, F. and Beutler, B (1996) The Tumor Necrosis Factor Ligand and Receptor Families. The New England Journal of Medicine, 334, 1717-1725. http://dx.doi.org/10.1056/NEJM199606273342607
[16]	Lipsky, P.E., Desiree, M.F.M., van der Heijde, D.M., et al. (2000) Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis. The New England Journal of Medicine, 343, 1594-1602. http://dx.doi.org/10.1056/NEJM200011303432202
[17]	Maini, R., St. Clair, E.W., Breedveld, F., et al. (1999) Infliximab (Chimeric Anti-Tumour Necrosis Factor α Monoclonal Antibody) versus Placebo in Rheumatoid Arthritis Patients Receiving Concomitant Methotrexate: A Randomized Phase III Trial. Lancet, 354, 1932-1939. http://dx.doi.org/10.1016/S0140-6736(99)05246-0
[18]	Smolen, J., Kay, J., Doyle, M.K., et al. (2009) Golimumab in Patients with Active Rheumatoid Arthritis after Treatment with Tumor Necrosis Alpha Inhibitors (GO-AFTER Study): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial. Lancet, 374, 210-221.
[19]	Kavanaugh, A., Smolen, J.S., Emery, P., et al. (2009) Effect of Certolizumab Pegol with Methotrexate on Home and Work Place Productivity and Social Activities in Patients with Active Rheumatoid Arthritis. Arthritis & Rheumatology, 15, 1592-1600.
[20]	Bean, A.G., Roach, D.R., Briscoe, H., et al. (1999) Structural Deficiencies in Granuloma Formation in TNF Gene-Targeted Mice Underlie the Heightened Susceptibility to Aerosol Mycobacterium Tuberculosis Infection. Journal of Immunology, 162, 3504-3511.
[21]	Ehlers, S., Benini, J., Kutsch, S., et al. (1999) Fatal Granuloma Necrosis Despite Intact Antibacterial Functions in TNFRp55-Deficient Mice Chronically Infected with M. Avium. Infection and Immunity, 67, 3571-3579.
[22]	Rothe, J., Lesslauer, W., Lotscher, H., et al. (1993) Mice Lacking the Tumour Necrosis Factor Receptor 1 Are Resistant to TNF-Mediated Toxicity but Highly Susceptible to Infection by Listeria Monocytogenes. Nature, 364, 798-802. http://dx.doi.org/10.1038/364798a0
[23]	Skerret, S.J., Bagby, G.J., Schmidt, R.A. and Nelson, S. (1997) Antibody-Mediated Depletion of Tumour Necrosis Factor-α Impairs Pulmonary Host Defenses to Legionella pneumophila. Journal of Infectious Diseases, 176, 1019-1028. http://dx.doi.org/10.1086/516530
[24]	Chen, W., Havell, E.A. and Harmsen, A.G. (1992) Importance of Endogenous Tumor Necrosis Factor and Gamma Interferon in Host Resistance Against Pneumocystis carinii Infection. Infection and Immunity, 60, 1279-1284.
[25]	Allendoerfer, R. and Deepe, G.S. (1998) Blockade of Endogenous TNF-α Exacerbates Primary and Secondary Pulmonary Histoplasmosis by Differential Mechanisms. Journal of Immunology, 160, 6072-6082.
[26]	Wolfe, F., Michaud, K., Anderson, J. and Urbansky, K. (2004) Tuberculosis Infection in Patients with Rheumatoid Arthritis and the Effect of Infliximab Therapy. Arthritis & Rheumatology, 50, 372-379. http://dx.doi.org/10.1002/art.20009
[27]	Wolfe, F. and Michaud, K. (2004) Lymphoma in Rheumatoid Arthritis: The Effect of Methotrexate and Anti-Tumor Necrosis Factor Therapy in 18,572 Patients. Arthritis & Rheumatology, 50, 1740-1751. http://dx.doi.org/10.1002/art.20311
[28]	Askling, J., Fored, C.M., Baeklung, E., et al. (2005) Haematopoietic Malignancies in Rheumatoid Arthritis: Lymphoma Risk and Characteristics after Exposure to Tumour Necrosis Factor Antagonists. Annals of the Rheumatic Diseases, 64, 1414-1420. http://dx.doi.org/10.1136/ard.2004.033241
[29]	Olsen, N.J. and Stein, C.M. (2004) New Drugs for Rheumatoid Arthritis. The New England Journal of Medicine, 350, 2167-2179. http://dx.doi.org/10.1056/NEJMra032906
[30]	Charles, P.J., Smeenk, R.J.T., De Jong, J., Feldmann, M. and Maini, R.N. (2000) Assessment of Antibodies to Double-Stranded DNA Induced in Rheumatoid Arthritis Patients Following Treatment with Infliximab, a Monoclonal Antibody to Tumor Necrosis Factor α: Findings in Open-Label and Randomized Placebo-Controlled Trials. Arthritis & Rheumatology, 43, 2383-2390. http://dx.doi.org/10.1002/1529-0131(200011)43:11<2383::AID-ANR2>3.0.CO;2-D
[31]	Mohan, N., Edwards, E.T., Cupps, T.R., et al. (2001) Demyelination Occurring During Anti-Tumor Necrosis Factor Alpha Therapy for Inflammatory Arthritides. Arthritis & Rheumatology, 44, 2862-2869. http://dx.doi.org/10.1002/1529-0131(200112)44:12<2862::AID-ART474>3.0.CO;2-W
[32]	van Oosten, B.W., Barkhof, F., Truyen, L., et al. (1996) Increased MRI Activity and Immune Activation in Two Multiple Sclerosis Patients Treated with Monoclonal Anti-Tumor Necrosis Factor Antibody cA2. Neurology, 47, 1531-1534. http://dx.doi.org/10.1212/WNL.47.6.1531
[33]	The Lenercept Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group (1999) TNF Neutralization in MS: Results of a Randomized, Placebo-Controlled Multicenter Study. Neurology, 53, 457-465. http://dx.doi.org/10.1212/WNL.53.3.457
[34]	Wolfe, F. and Michaud, K. (2004) Heart Failure in Rheumatoid Arthritis: Rates, Predictors, and the Effect of Anti-TNF Therapy. The American Journal of Medicine, 116, 305-311. http://dx.doi.org/10.1016/j.amjmed.2003.09.039
[35]	Singh, J.A., Furst, D.E., Bharat, A., et al. (2012) 2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Anti-Rheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis Care & Research, 64, 625-639. http://dx.doi.org/10.1002/acr.21641
[36]	Misra, R., Sharma, B.L., Gupta, R., et al. (2008) Indian Rheumatology Association Consensus Statement on the Management of Adults with Rheumatoid Arthritis. Indian Journal of Rheumatology, 3, S1-S16. http://dx.doi.org/10.1016/S0973-3698(10)60373-1
[37]	Malaviya, A.N., Shankar, S., Arya, V., et al. (2010) Indian Rheumatology Association Consensus Statement on the Diagnosis and the Treatment of Axial Spondyloarthropathies. Indian Journal of Rheumatology, 5, 16-34. http://dx.doi.org/10.1016/S0973-3698(10)60531-6
[38]	Upadhyaya, S. (2012) Treatment of Early RA. Apollo Medicine, 9, 345-346. http://dx.doi.org/10.1016/j.apme.2012.09.005
[39]	Upadhyaya, S. (2012) Treatment of Established RA. Apollo Medicine, 9, 347-348. http://dx.doi.org/10.1016/j.apme.2012.09.006