篇名

類風濕性關節炎與免疫風濕疾病的生物製劑治療

並列篇名

Biologic Agents for Rheumatoid Arthritis and Other Rheumatic Diseases

DOI

10.6320/FJM.201807_22(4).0005

作者

吳建陞(Chien-Sheng Wu)

關鍵字

生物製劑 ; 類風溼性關節 ; 腫瘤壞死因子抑制劑 ; biologics ; rheumatoid arthritis ; TNF-inhibitors

出版品名稱

台灣醫學

卷期/出版年月

22卷4期

頁次

388 - 393

內容語文

繁體中文

中文摘要

類風濕性關節炎(rheumatoid arthritis)是一種慢性發炎疾病,會造成病人的痛苦與殘疾。從二十世紀開始時缺乏有效藥物,到二十世紀末免疫生物製劑的誕生,類風溼性關節炎是一個基礎研究轉化為臨床突破的重要疾病模式。腫瘤壞死因子抑制劑(TNF-alpha inhibitors)是第一種用於類風溼性關節炎的生物製劑,孕育其誕生的重要分子生物與免疫學知識在1970-80年代逐漸完備,包括生產單株抗體的融合瘤技術、腫瘤壞死因子特性的研究、與基因工程技術的進步,然而產品商業化的過程,不但需要分子生物免疫學的知識,也需要製藥產業的臨床試驗執行力與人類的想像力。抗腫瘤壞死藥物的誕生,進一步推動對於人類疾病致病機轉的了解,包括腫瘤壞死因子在肺結核免疫的角色,有無抗體結晶片段(Fe)分子造成藥物特性的差異,甚至抗藥抗體的相關知識發展。隨著腫瘤壞死因子抑制劑的成功,後續針對B细胞的莫須瘤(ntuonnab)、針對介白素六受25的安挺樂(tocilizumab)、與針對阻斷抗原呈現細胞與T细胞交互作用的恩瑞舒(abatacept)等各種藥物陸續誕生,都適用於類風溼性關節炎。這些藥物的誕生又深化了我們對於各種免疫细胞與分子作用機轉的了解。然而生物製劑的發展與治療也面臨各種挑戰,例如生物製劑在類風溼性關節炎的療效仍然有進步的空間;在各種伺機性感染如B型肝炎與肺結核的防治上,也將台灣醫界未來的挑戰與機會!

英文摘要

Rheumatoid arthritis (RA), a chronic inflammatory disease, is disabling for patients. From a lack of effective treatment in the early twentieth century till the birth of biologic agent in the end of twentieth century, the development of therapy for RA shows how basic science is applied in clinical treatment. The TNF-alpha inhibitor is the first biologic agent for RA. The biotechnology and immunology knowledge for the development of TNF-alpha inhibitors matured in 1970-80s, including the hybridoma technology, the physiologic effect of TNF-alpha, and the molecular biology. However, the commercialization of biologics needs not only the scientific knowledge but also the execution of clinical trials by pharmaceutical industries and the imagination of human beings. The invention of TNF inhibitors improves the understanding of the pathogenesis of RA, the role of TNF in tuberculosis immunity, the Fc portion in pharmacokinetic properties, and the effect of the anti-drug antibody. Following the success of TNF-inhibitors, other biologic agents (including rituximab that depletes B cells, tocilizumab against IL-6 receptor, and abatacept that blocks the interaction between T cells and antigen presenting cells) were invented and marketed. These medications increased our understanding of the role of the immune cells and molecules. However, there are still some challenges in the treatment of RA. For example, the treatment response of RA has its ceiling. The management of opportunistic infections such as tuberculosis and viral hepatitis is both a challenge and a chance for clinicians in Taiwan!

主題分類 醫藥衛生 > 醫藥衛生綜合
參考文獻
  1. Pennica D, Nedwin GE, Hayflick JS et al: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 1984;312:724-9. doi: 10.1038/312724a0
    連結:
  2. Yamasaki K, Taga T, Hirata Y et al: Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science (New York, NY) 1988;241:825-8. doi: 10.1126/science.3136546
    連結:
  3. Chu CQ, Field M, Feldmann M et al: Localization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis. Arthritis and rheumatism 1991;34:1125-32. doi: 10.1002/art.1780340908
    連結:
  4. Brennan FM, Chantry D, Jackson A et al: Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet (London, England) 1989;2:244-7. doi: 10.1016/S0140-6736(89)90430-3
    連結:
  5. Williams RO, Feldmann M, Maini RN: Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proceedings of the National Academy of Sciences of the United States of America 1992;89:9784-8. doi: 10.1073/pnas.89.20.9784
    連結:
  6. Maini RN, Breedveld FC, Kalden JR et al: 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 1998;41:1552-63. doi: 10.1002/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W
    連結:
  7. Feldmann M, Maini RN: Anti-TNF therapy, from rationale to standard of care: what lessons has it taught us? Journal of immunology (Baltimore, Md : 1950) 2010;185:791-4. doi: 10.4049/jimmunol.1090051
    連結:
  8. Balakumar P, Singh M: Anti-tumour necrosis factor-alpha therapy in heart failure: future directions. Basic Clin Pharmacol Toxicol 2006;99:391-7. doi: 10.1111/j.1742-7843.2006.pto_508.x
    連結:
  9. Souto A, Maneiro JR, Gomez-Reino JJ: Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases. Rheumatology (Oxford, England) 2016;55:523-34. doi: 10.1093/rheumatology/kev374
    連結:
  10. Burmester GR, Bijlsma JWJ, Cutolo M et al: Managing rheumatic and musculoskeletal diseases - past, present and future. Nat Rev Rheumatol 2017;13:443-8. doi: 10.1038/nrrheum.2017.95
    連結:
  11. Wu CS: Impact of Immune Biological Agents on the Reactivation of Tuberculosis and Viral Hepatitis B and C. Formosan J Med 2013;17: 49-57. doi: 10.6838/YZU.2008.00312
    連結:
  12. Carmona L, Gomez-Reino JJ, Rodriguez- Valverde V et al: Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis and rheumatism 2005;52:1766-72. doi: 10.1002/art.21043
    連結:
  13. Wallis RS: Tumour necrosis factor antagonists: structure, function, and tuberculosis risks. Lancet Infect Dis 2008;8:601-11. doi: 10.1016/S1473-3099(08)70227-5
    連結:
  14. Yasukawa K, Hirano T, Watanabe Y et al: Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. The EMBO journal 1987;6:2939-45.
  15. Rondon E, Venkataraman R: Afelimomab led to a modest mortality benefit in patients with severe sepsis and elevated interleukin-6 levels. Crit Care 2005;9:E20.