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Understanding the major risk factors in the beginning and the progression of rheumatoid arthritis: current scenario and future prospects

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Abstract

Rheumatoid arthritis (RA), a chronic progressive inflammatory autoimmune disorder characterized by chronic pain and swelling primarily, affects the peripheral joints. RA had attained global concern in the last few decades, affecting more than 1.5 % of the world’s population with higher female percentage than male. In the advanced stage, the disease is associated with the destruction of cartilage and bone along with a variety of systemic manifestations leading to functional disability. Inadequate early/preliminary diagnosis and non-specific therapeutics are the major challenges in the management of RA. Till date, the exact cause(s) of the disease remain(s) obscure, and several genetic, hormonal, and environmental factors are associated with the beginning and the progression of the disease. Rheumatoid factor is the only clinically approved bio-marker for the diagnosis, and RA is not restricted to bones, but also affects several vital organs in the advanced stages. Genome-wide association studies have explored novel genetic loci underlying common autoimmune diseases including RA. Recent discoveries of risk alleles have made it possible to define genetic risk profiles of patients with RA. The conventional non-steroidal anti-inflammatory drugs and steroidal drugs are still the choice for the treatment of RA under acute and chronic pathological conditions respectively. However, disease-modifying anti-rheumatic drugs have shown remarkable success in the last decade. The present review provides a comprehensive understanding of the major risk factors and the molecular biology involved in the initiation and the progression of RA with a note on the recent trends in RA therapy.

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References

  1. Weyand CM, Goronzy JJ. The molecular basis of rheumatoid arthritis. J Mol Med (Berl). 1997;75(11–12):772–85.

    Article  CAS  PubMed  Google Scholar 

  2. Weyand CM, Klimiuk PA, Goronzy JJ. Heterogeneity of rheumatoid arthritis: from phenotypes to genotypes. Semin Immunopathol. 1998;20(1–2):5–22.

    Article  CAS  Google Scholar 

  3. Liao KP, Alfredsson L, Karlson EW. Environmental influences on risk for rheumatoid arthritis. Curr Opin Rheumatol. 2009;21(3):279–83.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Oliver JE, Silman AJ. Risk factors for the development of rheumatoid arthritis. Scand J Rheumatol. 2006;35(3):169–74.

    Article  CAS  PubMed  Google Scholar 

  5. Hoovestol RA, Mikuls TR. Environmental exposures and rheumatoid arthritis risk. Curr Rheumatol Rep. 2011;13(5):431–9.

    Article  CAS  PubMed  Google Scholar 

  6. Beydoun HA, Amin R, McNeal M, Perry C, Archer DF. Reproductive history and postmenopausal rheumatoid arthritis among women 60 years or older: Third National Health and Nutrition Examination Survey. Menopause. 2013;20(9):930–5.

    Article  PubMed  Google Scholar 

  7. Abasolo L, Tobías A, Leon L, et al. Weather conditions may worsen symptoms in rheumatoid arthritis patients: the possible effect of temperature. Reumatol Clin. 2013;9(4):226–8.

    Article  PubMed  Google Scholar 

  8. Smith HS, Smith AR, Seidner P. Painful rheumatoid arthritis. Pain Phys. 2011;14(5):E427–58.

    Google Scholar 

  9. van Laar M, Pergolizzi Jr JV et al. Pain treatment in arthritis-related pain: beyond NSAIDs. Open Rheumatol J. 2012; 6: 320–330.

  10. Chen YF, Jobanputra P, et al. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess. 2008;12(11):1–278.

    Article  PubMed  Google Scholar 

  11. Dennison EM, Cooper C. Corticosteroids in rheumatoid arthritis-effective anti-inflammatory agents, but doubts about safety remains. BMJ. 1998;316(7134):789–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Buckley LM. Clinical and diagnostic features of glucocorticoids-induced osteoporosis. Clin Exp Rheumatol. 2000;18(suppl. 21):S41–3.

    Google Scholar 

  13. Vreden SGS, Hermus ARMM, Van Lies-Sum PA, et al. Aseptic bone necrosis in patients on glucocorticoid replacement therapy. Neth J Med. 1991;39:153–7.

    CAS  PubMed  Google Scholar 

  14. Saag KG. Glucocorticoid use in rheumatoid arthritis, Curr Rheumatol Rep 2002; 4(3):218–225.

  15. Jobanputra P, Wilson J, Douglas K, Burls A. A survey of British rheumatologists’ DMARD preferences for rheumatoid arthritis. Rheumatology (Oxford). 2004;43(2):206–10.

    Article  CAS  Google Scholar 

  16. Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73:492–509.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Van der Heijde DM, van Riel PL, Nuver-Zwart, et al. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet 1989; 1:1036–1038.

  18. Van Riel PL, Van Gestel AM, Van De Putte LB. Long-term usage and side-effect profile of sulphasalazine in rheumatoid arthritis. Br J Rheumatol. 1995;34(2):40–2.

    Article  PubMed  Google Scholar 

  19. Cameron M, Gagnier JJ, Chrubasik S. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2011; 16;(2):CD002948. doi:10.1002/14651858.CD002948.pub2.

  20. Davis John M, Matteson Eric L. My treatment approach to rheumatoid arthritis. Mayo Clin Proc. 2012;87(7):659–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Tamhane A, McGwin G Jr, Redden DT, et al. Complementary and alternative medicine use in African Americans with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2014;66(2):180–9.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Bax M, van Heemst J, Huizinga TW, Toes RE. Genetics of rheumatoid arthritis: what have we learned? Immunogenetics. 2011;63(8):459–66.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Hui Alexander Y, McCarty William J, et al. Systems biology approach to synovial joint lubrication in health, injury, and disease. Wiley Interdiscip Rev Syst Biol Med. 2012;4(1):15–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Warrington KJ, Takemura S, Goronzy JJ, Weyand CM. CD4+, CD28-T cells in rheumatoid arthritis patients combines features of the innate and adaptive immune systems. Arthritis Rheum. 2011;44(1):13–20.

    Article  Google Scholar 

  25. Cope AP, Schulze-Koops H, Aringer M. The central role of T cells in rheumatoid arthritis. Clin Exp Rheumatol. 2007;25(5 Suppl 46):S4–11.

    CAS  PubMed  Google Scholar 

  26. Bläss S, Engel JM, Burmester GR. The immunologic homunculus in rheumatoid arthritis. A new viewpoint of immunopathogenesis in rheumatoid arthritis and therapeutic consequences. Z Rheumatol. 2001;60(1):1–16.

    Article  PubMed  Google Scholar 

  27. Marston B, Palanichamy A, Anolik JH. B cells in the pathogenesis and treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2010;22(3):307–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Kotzin BL. The role of B cells in the pathogenesis of rheumatoid arthritis. J Rheumatol Suppl. 2005; 73:14–8 (Discussion 29–30).

  29. Montecucco F, Mach F. Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthritis and atherosclerosis. Rheumatology (Oxford). 2009;48(1):11–22.

    Article  CAS  Google Scholar 

  30. El-Kady IM, El-Masry SA. Pro-inflammatory and anti-inflammatory cytokine profile in rheumatoid arthritis patients. Egypt J Immunol. 2008;15(1):109–14.

    PubMed  Google Scholar 

  31. Meyer O. Role of TNF-alpha and cytokines in the physiopathology of rheumatoid arthritis. Therapeutic perspectives. Bull Acad Natl Med. 2003;187(5):935–54 (Discussion 954–5).

  32. Tamer Mahmoud Tamer. Hyaluronan and synovial joint: function, distribution and healing. Interdiscip Toxicol. 2013;6(3):111–25. doi:10.2478/intox-2013-0019.

    PubMed Central  PubMed  Google Scholar 

  33. Bala A, Haldar PK. Free radical biology in cellular inflammation related to rheumatoid arthritis. OA Arthritis. 2013;1(2):15.

    Article  Google Scholar 

  34. Jürgen S et al. Cartilage degradation by stimulated human neutrophils: reactive oxygen species decrease markedly the activity of proteolytic enzymes. Chem Biol. 2000; 7(8);557–568.

  35. Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397–440.

    Article  CAS  PubMed  Google Scholar 

  36. Kowanko IC, Bates EJ, Ferrante A. Mechanism of human neutrophil-mediated cartilage damage in vitro; the role of lysosomal enzymes, hydrogen peroxide and hypochlorous acid. Immunol Cell Biol. 1989;67:321–9. doi:10.1038/icb.1989.47.

    Article  CAS  PubMed  Google Scholar 

  37. Ferucci ED, Templin DW, Lanier AP. Rheumatoid arthritis in American Indians and Alaska Natives: a review of the literature. Semin Arthritis Rheum. 2005;34(4):662–7.

    Article  PubMed  Google Scholar 

  38. Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 4 Suppl 2002; 3:S265–272.

  39. Tobon GJ, Youinou P, Saraux A. The environment, geo-epidemiology, and autoimmune disease: rheumatoid arthritis. J Autoimmun. 2010;35(1):10–4.

    Article  PubMed  Google Scholar 

  40. Toledano E, Candelas G, Rosales Z, Martínez Prada C, León L, et al. A meta-analysis of mortality in rheumatic diseases. Reumatol Clin. 2012;8(6):334–41.

    Article  PubMed  Google Scholar 

  41. Carmona L, Cross M, Williams B, Lassere M, March L. Rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2012;24(6):733–45. doi:10.1016/j.berh.2010.10.001.

    Article  Google Scholar 

  42. Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum Dis Clin N Am. 2001;27(2):269–81.

    Article  CAS  Google Scholar 

  43. Sokka T, et al. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study. Arthritis Res Ther. 2009;11(1):R7.

    PubMed Central  PubMed  Google Scholar 

  44. Majka DS, Holers VM. Can we accurately predict the development of rheumatoid arthritis in the preclinical phase? Arthritis Rheum. 2003; 48:2701–275.

  45. Vonkaman HE, van de Laar MAFJ. The new European league against rheumatism/American college of rheumatology diagnostic criteria for Rheumatoid arthritis—how are they performing? Curr Opin Rheumatol. 2013;25(3):354–9.

    Article  Google Scholar 

  46. Aletaha D, Neogi T, Silman AJ, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569–81.

    Article  PubMed  Google Scholar 

  47. Carrasco R, Barton A. Biomarkers of outcome in rheumatoid arthritis. Rheumatol Rep. 2010;2(e3):26–38.

    CAS  Google Scholar 

  48. Van Venrooij WJ, Van Beers JJ, Pruijn GJ. Anti-CCP antibody, a marker for the early detection of rheumatoid arthritis. Ann N Y Acad Sci. 2008;1143:268–85. doi:10.1196/annals.1443.013.

    Article  PubMed  Google Scholar 

  49. Maneiro RJ, Salgado E, Carmona L, Gomez-Reino JJ. Rheumatoid factor as predictor of response to abatacept, rituximab and tocilizumab in rheumatoid arthritis: systematic review and meta-analysis. Semin Arthritis Rheum. 2013;43(1):9–17. doi:10.1016/j.semarthrit.2012.11.007.

    Article  CAS  PubMed  Google Scholar 

  50. Bongartz T, Cantaert T, Atkins SR, Harle P, Myers JL, et al. Citrullination in extra-articular manifestations of rheumatoid arthritis. Rheumatology. 2007;46(1):70–5.

    Article  CAS  PubMed  Google Scholar 

  51. Mody GM, Cardiel MH. Challenges in the management of rheumatoid arthritis in developing countries. Best Pract Res Clin Rheumatol. 2008;22(4):621–41.

    Article  PubMed  Google Scholar 

  52. Kalla AA, Tikly M. Rheumatoid arthritis in the developing world. Best Pract Res Clin Rheumatol. 2003;17(5):863–75.

    Article  PubMed  Google Scholar 

  53. Vossenaar ER, Zendman AJ, Van Venroojj WJ, Pruijn GJ. PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. BioEssays. 2003;25(11):1106–18.

    Article  CAS  PubMed  Google Scholar 

  54. Nagai Y, Imanishi T. RA variome: a genetic risk variants database for rheumatoid arthritis based on assessment of reproducibility between or within human populations. Database (Oxford). 2013; 2013:bat073.

  55. Vossenaar ER, Van Venrooij WJ. Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res Ther. 2004;6:107–11. doi:10.1186/ar1184.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Vossenaar ER, Nijenhuis S, Helsen MM, et al. Citrullination of synovial proteins in murine models of rheumatoid arthritis. Arthritis Rheum. 2003;48(9):2489–500.

    Article  CAS  PubMed  Google Scholar 

  57. Foulquier C, Sebbag M, Clavel C, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum. 2007;56(11):3541–53.

    Article  CAS  PubMed  Google Scholar 

  58. Arita K, Hashimoto H, Shimizu T, et al. Structural basis for Ca2+-induced activation of human PAD4. Nat Struct Mol Biol. 2004;11:777–83. doi:10.1038/nsmb799.

    Article  CAS  PubMed  Google Scholar 

  59. Keilhoff G, Prell T, Langnaese K, Mawrin C, et al. Expression pattern of peptidylarginine deiminase in rat and human Schwann cells. Dev Neurobiol. 2008;68(1):101–14.

    Article  CAS  PubMed  Google Scholar 

  60. Cherrington BD, Morency E, Struble AM, et al. Potential role for peptidylarginine deiminase 2 (PAD2) in citrullination of canine mammary epithelial cell histones. PLoS One. 2010;5(7):e11768.

    Article  PubMed Central  PubMed  Google Scholar 

  61. Du Y, Liu X, Guo JP, et al. Association between PADI4 gene polymorphisms and anti-cyclic citrullinated peptide antibody positive rheumatoid arthritis in a large Chinese Han cohort. Clin Exp Rheumatol. 2014;32(3):377–82.

    CAS  PubMed  Google Scholar 

  62. Abd-Allah SH, el-Shal AS, Shalaby SM, et al. PADI4 polymorphisms and related haplotype in rheumatoid arthritis patients. Jt Bone Spine. 2012;79(2):124–128.

  63. Rohrbach Amanda S, Hemmers Saskia, et al. PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis. Arthritis Res Ther. 2012;14(3):R104.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Janeway Jr CA, Travers P, Walport M, et al. The major histocompatibility complex and its functions in immunobiology: the immune system in health and disease, 5th edn. 2001; New York: Garland Science.

  65. Fernando MMA, Christine R, et al. Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet. 2008;4(4):e1000024. doi:10.1371/journal.pgen.1000024.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Kruskall MS. The major histocompatibility complex: the value of extended haplotypes in the analysis of associated immune diseases and disorders. Yale J Biol Med. 1990;63(5):477–86.

    PubMed Central  CAS  PubMed  Google Scholar 

  67. Vignal C, Bansal AT, Balding DJ, et al. The genetic association of the major histocompatibility complex with rheumatoid arthritis implicates two non-DRB1 loci. Arthritis Rheum. 2009;60(1):53–62.

    Article  CAS  PubMed  Google Scholar 

  68. Lich JD, Jayne JA, Zhou D, et al. Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM. J Immunol. 2003;171:853–9.

    Article  CAS  PubMed  Google Scholar 

  69. Jenkins SC, March RE, Campbell RD, Milner CM. A novel variant of the MHC-linked hsp70, hsp70-hom, is associated with rheumatoid arthritis. Tissue Antigens. 2000;56(1):38–44.

    Article  CAS  PubMed  Google Scholar 

  70. Salama A, Elshazli R, Elsaid A, Settin A. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) +1858 C>T gene polymorphism in Egyptian cases with rheumatoid arthritis. Cell Immunol. 2014;290(1):62–5. doi:10.1016/j.cellimm.2014.05.003.

    Article  CAS  PubMed  Google Scholar 

  71. Burn Garth L, Svensson Lena, Sanchez-Blanco Cristina, et al. Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? Autoimmunity: rheumatoid arthritis & multiple sclerosis. FEBS Lett. 2011;585(230):3689–98.

    Article  CAS  PubMed  Google Scholar 

  72. Torres-Carrillo NM, Ruiz-Noa Y, et al. The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in a Mexican population of Western Mexico. Immunol Lett. 2012;147(1–2):41–6.

    Article  CAS  PubMed  Google Scholar 

  73. Smyth DJ, Cooper JD, Howson JM, et al. PTPN22 Trp620 explains the association of chromosome 1p13 with type 1 diabetes and shows a statistical interaction with HLA class II genotypes. Diabetes. 2008;57(6):1730–937.

    Article  CAS  PubMed  Google Scholar 

  74. Kokkonen H, Johansson M, Innala L, Jidell E, Rantapaa-Dahlqvist S. The PTPN22 1858C/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden. Arthritis Res Ther. 2007;9(3):R56.

    Article  PubMed Central  PubMed  Google Scholar 

  75. Weyand CM, Goronzy JJ. T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006;2(4):201–10.

    Article  CAS  PubMed  Google Scholar 

  76. McCoy KD, Le Gros G. The role of CTLA-4 in the regulation of T cell immune responses. Immunol Cell Biol. 1999;77:1–10.

    Article  CAS  PubMed  Google Scholar 

  77. MacKenzie NM. New therapeutics that treat rheumatoid arthritis by blocking T-cell activation. Drug Discov Today. 2006;11(19–20):952–6.

    Article  CAS  PubMed  Google Scholar 

  78. Liu CP, Jiang JA, Wang T, Liu XM, et al. CTLA-4 and CD86 genetic variants and haplotypes in patients with rheumatoid arthritis in southeastern China. Genet Mol Res. 2013; 25;12(2):1373–1382.

  79. Sabahi R, Anolik JH. B-cell-targeted therapy for systemic lupus erythematosus. Drugs. 2006;66(15):1933–48.

    Article  PubMed  Google Scholar 

  80. Daha NA, Kurreeman FA, Marques RB, et al. Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis. Arthritis Rheum. 2009;60(5):1255–60.

    Article  PubMed  Google Scholar 

  81. Li G, Shi F, Liu J, Li Y. The effect of CTLA-4 A49G polymorphism on rheumatoid arthritis risk: a meta-analysis. Diagn Pathol. 2014;9:157.

    Article  PubMed Central  PubMed  Google Scholar 

  82. Moreland LW, et al. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. 2002;46(6):1470–9.

    Article  CAS  PubMed  Google Scholar 

  83. Tong G, Zhang X, Tong W, Liu Y. Association between polymorphism in STAT4 gene and risk of rheumatoid arthritis: a meta-analysis. Hum Immunol. 2013;74(5):586–92.

    Article  CAS  PubMed  Google Scholar 

  84. Li H, Zou Q, Xie Z, Liu Y, Zhong B, et al. A haplotype in STAT4 gene associated with rheumatoid arthritis in Caucasians is not associated in the Han Chinese population, but with the presence of rheumatoid factor. Rheumatology (Oxford). 2009;48(11):1363–8.

    Article  CAS  Google Scholar 

  85. Wang KS, Zorn E, Ritz J. Specific down-regulation of interleukin-12 signaling through induction of phospho-STAT4 protein degradation. Blood. 2001;97:3860–6.

    Article  CAS  PubMed  Google Scholar 

  86. Settin A, Salama A, Elshazli R. Signal transducer and activator of transcription 4 (STAT4) G>T gene polymorphism in Egyptian cases with rheumatoid arthritis. Hum Immunol. 2014;75(8):863–6.

    Article  CAS  PubMed  Google Scholar 

  87. Jiang X, Zhou Z, Zhang Y, Yang H, Ren K. An updated meta-analysis of the signal transducer and activator of transcription 4 (STAT4) rs7574865 G/T polymorphism and rheumatoid arthritis risk in an Asian population. Scand J Rheumatol. 2014;43(6):477–80. doi:10.3109/03009742.2014.918174.

    Article  CAS  PubMed  Google Scholar 

  88. Liang YL, Wu H, Li PQ, et al. Signal transducer and activator of transcription 4 gene polymorphisms associated with rheumatoid arthritis in the Northwestern Chinese Han population. Life Sci. 2011; 1;89(5–6):171–175.

  89. Shen L, Liu R, Zhang H, Huang Y, Sun R, Tang P. Replication study of STAT4 rs7574865 G/T polymorphism and risk of rheumatoid arthritis in a Chinese population. Gene. 2013;526(2):259–64.

    Article  CAS  PubMed  Google Scholar 

  90. Peng H, Wang W, Zhou M, et al. Associations of interleukin-4 receptor gene polymorphisms (Q551R, I50V) with rheumatoid arthritis: evidence from a meta-analysis. Genet Test Mol Biomark. 2013;17(10):768–74.

    Article  CAS  Google Scholar 

  91. Lee YH, Woo JH, et al. Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis: a meta-analysis. Rheumatol Int. 2009;30(5):661–6. doi:10.1007/s00296-009-1051-z.

    Article  CAS  PubMed  Google Scholar 

  92. Gu E, Lu J, Xing D, Chen X, et al. Rs7574865 polymorphism in signal transducers and activators of transcription 4 gene and rheumatoid arthritis: an updated meta-analysis of 28 case-control comparisons. Int J Rheum Dis. 2014;1:19. doi:10.1111/1756-185X.12363.

    Google Scholar 

  93. Gardiner TA, Gibson DS, et al. Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy. Am J Pathol. 2005;166(2):637–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Feldmann M, Maini RN. Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol. 2001;19:163–96.

    Article  CAS  PubMed  Google Scholar 

  95. McCluggage LK, Scholtz JM. Golimumab: a tumor necrosis factor alpha inhibitor for the treatment of rheumatoid arthritis. Ann Pharmacother. 2010;44(1):135–44.

    Article  CAS  PubMed  Google Scholar 

  96. Wijngaarden S, van de Winkel JG, et al. Treatment of rheumatoid arthritis patients with anti-TNF-alpha monoclonal antibody is accompanied by down-regulation of the activating Fcgamma receptor I on monocytes. Clin Exp Rheumatol. 2008;26(1):89–95.

    CAS  PubMed  Google Scholar 

  97. Toussirot E, Wendling D. The use of TNF-alpha blocking agents in rheumatoid arthritis: an update. Expert Opin Pharmacother. 2007;8(13):2089–107.

    Article  CAS  PubMed  Google Scholar 

  98. Pérez-Zafrilla B, Carmona L, Gómez-Reino JJ. Infections in patients with rheumatic diseases treated with TNF antagonists. Curr Pharm Biotechnol. 2012;13(8):1418–25.

    Article  PubMed  Google Scholar 

  99. Chakravarty SD, Poulikakos PI, et al. Kinase inhibitors: a new tool for the treatment of rheumatoid arthritis. Clin Immunol. 2013;148(1):66–78. doi:10.1345/aph.1M227.

    Article  CAS  PubMed  Google Scholar 

  100. Vaddi K, Luchi M. JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral DMARD therapy. Expert Opin Investig Drugs. 2012;21(7):961–73. doi:10.1517/13543784.2012.690029.

    Article  CAS  PubMed  Google Scholar 

  101. Scott LJ. Tofacitinib—a review of its use in adult patients with rheumatoid arthritis. Drugs. 2013;73(8):857–74.

    Article  CAS  PubMed  Google Scholar 

  102. Daien CI, Morel J. Predictive factors of response to biological disease modifying antirheumatic drugs: towards personalized medicine. Med. Inflamm. 2014(article ID 386148): 1–11. doi:10.1155/2014/386148.

  103. Gonzalez-Alvaro I, Carmona L, Balsa A, Sanmarti R, et al. Patterns of disease modifying antirheumatic drug use in a Spanish cohort of patients with rheumatoid arthritis. J Rheumatol. 2013;30(4):697–704.

    Google Scholar 

  104. Valleala H, Korpela M, Möttönen T, Hienonen-Kempas T et al. Rituximab therapy in patients with rheumatoid arthritis refractory or with contraindication to anti-tumour necrosis factor drugs: real-life experience in Finnish patients. Scand J Rheumatol. 2009;38(5):323–327.

  105. Quan L, Thiele GM, Tian J, Wang D. The development of novel therapies for rheumatoid arthritis. Expert Opin Ther Pat. 2008;18(7):723–38. doi:10.1517/13543776.18.7.723.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Ernst E, Posadzki P. Complementary and alternative medicine for rheumatoid arthritis and osteoarthritis: an overview of systematic reviews. Curr Pain Headache Rep. 2011;15(6):431–7. doi:10.1007/s11916-011-0227-x.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank the Principal and the management of R.V.R. & J.C. College of Engineering (A), Guntur, India for providing support to the current study. Further, the authors owe their deep gratitude to Professor Subrato Kumar Dey, School of Biological Sciences and Biotechnology, West Bengal University of Technology, Kolkata, India for his technical support. Also, the authors place on record their sincere thanks to Dr. P. Yamini and Dr. R. Vidyadhar, Faculty in English, for language assistance in preparing the manuscript.

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  1. Department of Biotechnology, RVR & JC College of Engineering (A), Guntur, 522 019, Andhra Pradesh, India

    Mahendra Kumar Verma & Kota Sobha

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Verma, M.K., Sobha, K. Understanding the major risk factors in the beginning and the progression of rheumatoid arthritis: current scenario and future prospects. Inflamm. Res. 64, 647–659 (2015). https://doi.org/10.1007/s00011-015-0843-8

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