A novel treatment option in rheumatoid arthritis: Abatacept, a selective modulator of T-cell co-stimulation

被引:2
作者
Dejaco C. [1 ]
Duftner C. [1 ]
Wipfler E. [1 ]
Schirmer M. [1 ,2 ]
机构
[1] Abteilung für Innere Medizin, Krankenhaus der Elisabethinen, Klagenfurt
[2] Abteilung FürInnere Medizin, Krankenhaus der Elisabethinen, 9020 Klagenfurt
关键词
Abatacept; Biologics; Rheumatoid arthritis;
D O I
10.1007/s10354-008-0590-3
中图分类号
学科分类号
摘要
Abatacept is the first drug in a new class of disease-modifying anti-rheumatic drugs known as selective modulators of T-cell costimulation. The efficacy of abatacept in the treatment of rheumatoid arthritis (RA) has been shown in several clinical phase II and phase III trials, wherein abatacept was used in monotherapy, either in combination with methotrexate (MTX) after MTX-failure, in combination with MTX after failure of anti-TNF-α therapy or in combination with TNF-α blockers. In addition, the combination of abatacept/MTX was directly compared with infliximab/MTX. Current data on abatacept demonstrate an encouraging safety profile of this drug. The number of adverse events in patients on abatacept is comparable to that in patients treated with other biologics. Severe infections, however, are more common in abatacept-treated patients than in placebo-treated patients. Opportunistic infections are rare in patients with abatacept and the frequency of malignancies is not higher than expected in RA-patients. Additional studies are now warranted to get more information on rare adverse events and long-term unwanted effects. © 2009 Springer-Verlag.
引用
收藏
页码:70 / 75
页数:5
相关论文
共 38 条
[11]  
Salomon B., Lenschow D.J., Rhee L., Ashourian N., Singh B., Sharpe A., Bluestone J.A., B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes, Immunity, 12, pp. 431-440, (2000)
[12]  
Dejaco C., Duftner C., Grubeck-Loebenstein B., Schirmer M., Imbalance of regulatory T cells in human autoimmune diseases, Immunology, 117, pp. 289-300, (2006)
[13]  
Vallejo A.N., CD28 extinction in human T cells: Altered functions and the program of T-cell senescence, Immunol Rev, 205, pp. 158-169, (2005)
[14]  
Schirmer M., Vallejo A.N., Weyand C.M., Goronzy J.J., Resistance to apoptosis and elevated expression of Bcl-2 in clonally expanded CD4 + CD28 - T cells from rheumatoid arthritis patients, J Immunol, 161, pp. 1018-1025, (1998)
[15]  
Schmidt D., Goronzy J.J., Weyand C.M., CD4+ CD7 - CD28 - T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity, J Clin Invest, 97, pp. 2027-2037, (1996)
[16]  
Namekawa T., Snyder M.R., Yen J.H., Goehring B.E., Leibson P.J., Weyand C.M., Goronzy J.J., Killer cell activating receptors function as costimulatory molecules on CD4 + CD28null T cells clonally expanded in rheumatoid arthritis, J Immunol, 165, pp. 1138-1145, (2000)
[17]  
Moreland L.W., Alten R., Van Den Bosch F., Appelboom T., Leon M., Emery P., Cohen S., Luggen M., Shergy W., Nuamah I., Becker J.C., Costimulatory blockade in patients with rheumatoid arthritis: A pilot, dosefinding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion, Arthritis Rheum, 46, pp. 1470-1479, (2002)
[18]  
Kremer J.M., Westhovens R., Leon M., Di Giorgio E., Alten R., Steinfeld S., Russell A., Dougados M., Emery P., Nuamah I.F., Williams G.R., Becker J.C., Hagerty D.T., Moreland L.W., Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig, N Engl J Med, 349, pp. 1907-1915, (2003)
[19]  
Kremer J.M., Dougados M., Emery P., Durez P., Sibilia J., Shergy W., Steinfeld S., Tindall E., Becker J.C., Li T., Nuamah I.F., Aranda R., Moreland L.W., Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: Twelve-month results of a phase iib, doubleblind, randomized, placebo-controlled trial, Arthritis Rheum, 52, pp. 2263-2271, (2005)
[20]  
Weinblatt M., Schiff M., Goldman A., Kremer J., Luggen M., Li T., Chen D., Becker J.C., Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: A randomised clinical trial, Ann Rheum Dis, 66, pp. 228-234, (2007)