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Biologic Drugs and Small Molecules for an Elderly Patient with the Rheumatic Disease

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Rheumatic Disease in Geriatrics
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Abstract

Rheumatic diseases are common in elderly and may present differently from the younger population. Nevertheless, treatment goals must be similar in all ages. The majority of studies have shown the similar efficacy and safety profile of biological therapies in the elderly patients with rheumatic disease and in their younger counterparts. However, the rate of severe adverse events, including severe infections, can be increased in elderly persons, particularly those aged 75 years or more. One of the strategies for choosing the right anti-rheumatic biologic drug for an elderly with multiple co-morbidities, in the era of multiple biologic medicines and small molecules with similar efficacy, can be based on patient’s background and the known safety profile of the therapeutics.

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References

  1. Tutuncu Z, Reed G, Kremer J, Kavanaugh A. Do patients with older-onset rheumatoid arthritis receive less aggressive treatment? Ann Rheum Dis. 2006;65:1226–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Payet S, Soubrier M, Perrodeau E, Bardin T, Cantagrel A, Combe B, et al. Efficacy and safety of rituximab in elderly patients with rheumatoid arthritis enrolled in a French Society of Rheumatology registry. Arthritis Care Res. 2014;66:1289–95.

    Article  CAS  Google Scholar 

  3. Soubrier M, Mathieu S, Payet S, Dubost JJ, Ristori JM. Elderly-onset rheumatoid arthritis. Joint Bone Spine. 2010;77:290–6.

    Article  PubMed  Google Scholar 

  4. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum. 2006;54:628–34.

    Article  CAS  PubMed  Google Scholar 

  5. Grijalva CG, Kaltenbach L, Arbogast PG, Mitchel EF Jr, Griffin MR. Initiation of rheumatoid arthritis treatments and the risk of serious infections. Rheumatology. 2010;49:82–90.

    Article  CAS  PubMed  Google Scholar 

  6. Solomon DH, Avorn J, Katz JN, et al. Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:3790–8.

    Article  CAS  PubMed  Google Scholar 

  7. Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2016;68:1–25.

    Article  Google Scholar 

  8. Baddley JW, Cantini F, Goletti D, Gómez-Reino JJ, Mylonakis E, San-Juan R. ESCMID study group for infections in compromised hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents). Clin Microbiol Infect. 2018;24(Suppl 2):S10–20.

    Article  CAS  PubMed  Google Scholar 

  9. Sanchez-Cano D, Callejas-Rubio JL, Ruiz-Villaverde R, RiosFernandez R, Ortego-Centeno N. Off-label uses of anti-TNF therapy in three frequent disorders: Behçet’s disease, sarcoidosis, and noninfectious uveitis. Mediat Inflamm. 2013;2013:286857.

    Article  CAS  Google Scholar 

  10. Vallet H, Riviere S, Sanna A, et al. Efficacy of anti-TNF alpha in severe and/ or refractory Behçet’s disease: multicenter study of 124 patients. J Autoimmun. 2015;62:67–74.

    Article  CAS  PubMed  Google Scholar 

  11. Pritchard C, Nadarajah K. Tumour necrosis factor alpha inhibitor treatment for sarcoidosis refractory to conventional treatments: a report of five patients. Ann Rheum Dis. 2004;63:318–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hoffman GS, Merkel PA, Brasington RD, Lenschow DJ, Liang P. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum. 2004;50:2296–304.

    Article  CAS  PubMed  Google Scholar 

  13. Lamprecht P. TNF-alpha inhibitors in systemic vasculitides and connective tissue diseases. Autoimmun Rev. 2005;4(1):28–34.

    Article  CAS  PubMed  Google Scholar 

  14. Aaltonen KJ, Virkki LM, Malmivaara A, et al. Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis. PLoS One. 2012;7:e30275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Galloway JB, Hyrich KL, Mercer LK, Dixon WG, Fu B, Ustianowski AP, et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology. 2011;50:124–31.

    Article  CAS  PubMed  Google Scholar 

  16. Köller MD, Aletaha D, Funovits J, Pangan A, Baker D, Smolen JS. Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients. Rheumatology. 2009;48:1575–80.

    Article  PubMed  CAS  Google Scholar 

  17. Filippini M, Bazzani C, Favalli EG, et al. Efficacy and safety of anti-tumour necrosis factor in elderly patients with rheumatoid arthritis: an observational study. Clin Rev Allergy Immunol. 2010;38:90–6.

    Article  CAS  PubMed  Google Scholar 

  18. Radovits BJ, Kievit W, Fransen J, et al. Influence of age on the outcome of antitumour necrosis factor alpha therapy in rheumatoid arthritis. Ann Rheum Dis. 2009;68:1470–3.

    Article  CAS  PubMed  Google Scholar 

  19. Genevay S, Finckh A, Ciurea A, Chamot AM, Kyburz D, Gabay C. Tolerance and effectiveness of anti-tumor necrosis factor alpha therapies in elderly patients with rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2007;57:679–85.

    Article  PubMed  Google Scholar 

  20. Cho SK, Sung YK, Kim D, Won S, Choi CB, Kim TH. Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid arthritis. BMC Musculoskelet Disord. 2016;17:333.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Dalal DS, Duran J, Brar T, Alqadi R, Halladay C, Lakhani A, Rudolph JL. Efficacy and safety of biological agents in the older rheumatoid arthritis patients compared to young: a systematic review and meta-analysis. Semin Arthritis Rheum. 2019;48:799–807.

    Article  CAS  PubMed  Google Scholar 

  22. van der Linden MP, le Cessie S, Raza K, van der Woude D, Knevel R, Huizinga TW, van der Helm-van Mil AH. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum. 2010;62(12):3537–46.

    Google Scholar 

  23. Radovits BJ, Fransen J, Eijsbouts A, van Riel PLCM, Laan RFJM. Missed opportunities in the treatment of elderly patients with rheumatoid arthritis. Rheumatology. 2009;48:906–10.

    Article  PubMed  Google Scholar 

  24. Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH. Chapter 63: Tumor necrosis factor – blocking therapies. In: Rheumatology. 6th ed. Maryland Heights, MO: Mosby Elsevier; 2015. p. 492–510.

    Google Scholar 

  25. Scott LJ. Tocilizumab: a review in rheumatoid arthritis. Drugs. 2017;77:1865–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Specker C, Kaufmann J, Kellner H, Kaestner P, Volberg C, Braunewell V, et al. Safe and effective tocilizumab therapy in elderly patients with rheumatoid arthritis [abstract no. FRI0202]. Ann Rheum Dis. 2016;75(Suppl 2):504.

    Article  Google Scholar 

  27. Pers YM, Schaub R, Constant E, Lambert J, Godfrin-Valnet M, Fortunet C, et al. Efficacy and safety of tocilizumab in elderly patients with rheumatoid arthritis. Joint Bone Spine. 2015;82(1):25–30.

    Article  CAS  PubMed  Google Scholar 

  28. Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377:317–28.

    Article  CAS  PubMed  Google Scholar 

  29. https://www.ema.europa.eu/en/documents/product-information/kevzara-epar-product-information_en.pdf.

  30. Fleischmann R, Genovese MC, van Adelsberg J, et al. Pooled safety and efficacy of sarilumab in rheumatoid arthritis patients 65 years of age and older [abstract]. Arthritis Rheumatol. 2016;68

    Google Scholar 

  31. Schioppo T, Ingegnoli F. Current perspective on rituximab in rheumatic diseases. Drug Des Dev Ther. 2017;11:2891–904.

    Article  CAS  Google Scholar 

  32. Vassilopoulos D, Delicha EM, Settas L, Andrianakos A, Aslanidis S, Boura P, et al. Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study. Clin Exp Rheumatol. 2016;34:893–900.

    PubMed  Google Scholar 

  33. Wendler J, Burmester GR, Sörensen H, Krause A, Richter C, Tony HP. Rituximab in patients with rheumatoid arthritis in routine practice (GERINIS): 6-year results from a prospective, multicentre, non-interventional study in 2,484 patients. Arthritis Res Ther. 2014;16:R80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Moc CC. Rituximab for the treatment of rheumatoid arthritis: an update. Drug Des Devel Ther. 2014;8:87–100.

    Google Scholar 

  35. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125370s064,761043s007lbl.pdf.

  36. Scott LJ, Burness CB, McCormack PL. Belimumab: a guide to its use in systemic lupus erythematosus. BioDrugs. 2012;26:195–9.

    Article  CAS  PubMed  Google Scholar 

  37. Blair HA, Duggan ST. Belimumab: a review in systemic lupus erythematosus. Drugs. 2018;78(3):355–66.

    Article  CAS  PubMed  Google Scholar 

  38. Takahashi N, Kojima T, Asai S, Watanabe T, Matsumoto T, Asai N, Sobue Y, Ishiguro N. Being elderly is not a predictive factor of discontinuation of abatacept due to adverse events in rheumatoid arthritis patients with concomitant methotrexate: a retrospective observational study based on data from a Japanese multicenter registry study [abstract]. Arthritis Rheumatol. 2017;69

    Google Scholar 

  39. Sekiguchi M, Fujii T, Matsui K, Murakami K, Morita S, Ohmura K, et al. Differences in predictive factors for sustained clinical remission with abatacept between younger and elderly patients with biologic-naive rheumatoid arthritis: results from the ABROAD study. J Rheumatol. 2016;43(11):1974–83.

    Article  CAS  PubMed  Google Scholar 

  40. Lahaye C, Soubrier M, Mulliez A, Bardin T, Cantagrel A, Combe B. Effectiveness and safety of abatacept in elderly patients with rheumatoid arthritis enrolled in the French Society of Rheumatology’s ORA registry. Rheumatology (Oxford). 2016;55(5):874–82.

    Article  CAS  Google Scholar 

  41. Hodge JA, Kawabata TT, Krishnaswami S, Clark JD, Telliez JB, Dowty ME. The mechanism of action of tofacitinib – an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016;34:318–28.

    PubMed  Google Scholar 

  42. Curtis JR, Schulze-Koops H, Takiya L, Mebus CA, Terry KK, Biswas P, Jones TV. Efficacy and safety of tofacitinib in older and younger patients with rheumatoid arthritis. Clin Exp Rheumatol. 2017;35:390–400.

    PubMed  Google Scholar 

  43. Winthrop KL, Curtis JR, Lindsey S, Tanaka Y, Yamaoka K, Valdez H, et al. Herpes zoster and tofacitinib: clinical outcomes and the risk of concomitant therapy. Arthritis Rheumatol. 2017;69:1960–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75:1843–7.

    Article  CAS  PubMed  Google Scholar 

  45. https://www.ema.europa.eu/en/documents/product-information/olumiant-epar-product-information_en.pdf.

  46. Fleischmann R, Alam J, Arora V, Bradley J, Schlichting DE, Muram D, et al. Safety and efficacy of baricitinib in elderly patients with rheumatoid arthritis. RMD Open. 2017;3:e000546.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373:1329–39.

    Article  CAS  PubMed  Google Scholar 

  48. Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler CL, et al. kizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebocontrolled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76:79–87.

    Article  CAS  PubMed  Google Scholar 

  49. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125504s013lbl.pdf.

  50. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125521s004lbl.pdf.

  51. Körber A, Papavassilis C, Bhosekar V, Reinhardt M. Efficacy and safety of secukinumab in elderly subjects with moderate to severe plaque psoriasis: a pooled analysis of phase III studies. Drugs Aging. 2018;35:135–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Di Lernia V, Goldust M. An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly. Expert Opin Biol Ther. 2018;18:897–903.

    Article  PubMed  CAS  Google Scholar 

  53. Gottlieb A, Narang K. Ustekinumab in the treatment of psoriatic arthritis: latest findings and clinical potential. Ther Adv Musculoskelet Dis. 2013;5:277–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. http://www.janssenlabels.com/package-insert/productmonograph/prescribing-information/STELARA-pi.pdf.

  55. Hayashi M, Umezawa Y, Fukuchi O, Ito T, Saeki H, Nakagawa H. Efficacy and safety of ustekinumab treatment in elderly patients with psoriasis. J Dermatol. 2014;41:974–80.

    Article  CAS  PubMed  Google Scholar 

  56. Bettiol A, Lopalco G, Emmi G, Cantarini L, Urban ML, Vitale A. Unveiling the efficacy, safety, and tolerability of anti-Interleukin-1 treatment in monogenic and multifactorial autoinflammatory diseases. Int J Mol Sci. 2019;20(8):1898.

    Article  CAS  PubMed Central  Google Scholar 

  57. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103950s5136lbl.pdf.

  58. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125319s047lbl.pdf.

  59. Keating GM. Apremilast: a review in psoriasis and psoriatic arthritis. Drugs. 2017 Mar;77:459–72.

    Article  CAS  PubMed  Google Scholar 

  60. Hatemi G, Mahr A, Ishigatsubo Y, Song YW, Takeno M, Kim D, et al. Trial of apremilast for oral ulcers in Behçet’s syndrome. N Engl J Med. 2019;381(20):1918–28.

    Article  CAS  PubMed  Google Scholar 

  61. Schafer PH, Chen P, Fang L, et al. The pharmacodynamic impact of apremilast, an oral phosphodiesterase 4 inhibitor, on circulating levels of inflammatory biomarkers in patients with psoriatic arthritis: substudy results from a phase III, randomized, placebo-controlled trial (PALACE 1). J Immunol Res. 2015;2015:906349.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Cutolo M, Myerson GE, Fleischmann RM, et al. A phase III, randomized, controlled trial of apremilast in patients with psoriatic arthritis: results of the PALACE 2 trial. J Rheumatol. 2016;43(9):1724–34.

    Article  PubMed  Google Scholar 

  63. Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75(6):1065–73.

    Article  CAS  PubMed  Google Scholar 

  64. https://media.celgene.com/content/uploads/otezla-pi.pdf.

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Ginsberg, S. (2020). Biologic Drugs and Small Molecules for an Elderly Patient with the Rheumatic Disease. In: Slobodin, G., Shoenfeld, Y. (eds) Rheumatic Disease in Geriatrics . Springer, Cham. https://doi.org/10.1007/978-3-030-44234-7_6

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  • DOI: https://doi.org/10.1007/978-3-030-44234-7_6

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