Medical treatment of rheumatoid arthritis (II): current biologic agents and newly developing drugs

Jinhyun Kim; Yeong-Wook Song

doi:10.5124/jkma.2010.53.10.880

Journal List > J Korean Med Assoc > v.53(10) > 1042331

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Kim and Song: Medical treatment of rheumatoid arthritis (II): current biologic agents and newly developing drugs

Focused Issue of This Month

Rheumatoid Arthritis

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2010; 53(10): 880-888.

Published online: 11 October 2010

DOI: https://doi.org/10.5124/jkma.2010.53.10.880

Medical treatment of rheumatoid arthritis (II): current biologic agents and newly developing drugs

Jinhyun Kim, MD, Yeong-Wook Song, MD

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Corresponding author: Yeong-Wook Song, ysong@snu.ac.kr

Received 11 August 2010 Accepted 15 August 2010

(open-access):

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Disease-modifying antirheumatic drugs (DMARD) have been used to treat rheumatoid arthritis (RA). However, they have limited efficacy and a considerable adverse event profile. Excess production of soluble cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, appears to mediate the chronic inflammation associated with RA. Clinical trials with targeted anticytokine biologic agents, including anti-TNFα antibodies (adalimumab, infliximab, golimumab, certolizumab), anti-IL-6 receptor antibodies (tocilizumab), and the soluble tumor necrosis factor-α receptor (etanercept), have shown remarkable efficacy in the treatment of RA. In addition, costimulatory blockade (abatacept) and B cell depletion (rituximab) have been employed as important adjunctive therapies in RA. Judicious use of these agents, considering their benefits and risks, would bring the greatest benefit to RA patients. The optimal conditions for the administration and indication of these drugs are under investigation. Signal transduction is another target of newly developing drugs. Because of the development of anti-TNF therapy and other biologics, there have been great advances in the treatment of RA.

Keywords: Rheumatoid arthritis, Cytokine, B cell depletion, Secondary signal, Kinase inhibitor

Acknowledgements

This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A084794).

References

1. Center for Biologics Evaluation and Research. "What is a biological product?". U.S. Food and Drug Administration. Accessed 2010-1-10. http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm133077.htm.

2. Stone JH. Overview of biologic agents in the rheumatic diseases. Uptodate. Accessed 2010-1-10. http://www.uptodateonline.com/online/content/topic.do?topicKey=treatme/11280.

3. Moreland LW. Cytokines as targets for anti-inflammatory agents. Ann N Y Acad Sci. 2009. 1182:88–96.

4. Kukar M, Petryna O, Efthimiou P. Biological targets in the treatment of rheumatoid arthritis: a comprehensive review of current and in-development biological disease modifying anti-rheumatic drugs. Biologics. 2009. 3:443–457.

5. Song JS. Review of Tumor Necrosis Factor Inhibitors on Rheumatoid Arthritis. J Korean Rheum Assoc. 2007. 14:1–14.

6. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet. 1999. 354:1932–1939.

7. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000. 343:1594–1602.

8. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martín Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M. TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004. 363:675–681.

9. Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, Fischkoff SA, Chartash EK. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004. 50:1400–1411.

10. St Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P, Keystone E, Schiff M, Kalden JR, Wang B, Dewoody K, Weiss R, Baker D. Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset Study Group. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004. 50:3432–3443.

11. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006. 54:26–37.

12. Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig AS, Freundlich B. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008. 372:375–382.

13. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006. 295:2275–2285.

14. Guidelines for treatment of latent tuberculosis in patients treated with TNF-alpha blockers. Korea Food and Drug Administration. Accessed 2010-1-10. http://www.kfda.go.kr/index.kfda?mid=70&pageNo=4&cd=147&cmd=v&seq=4281.

15. Chung SJ, Kim JK, Park MC, Park YB, Lee SK. Reactivation of hepatitis B viral infection in inactive HBsAg carriers following anti-tumor necrosis factor-alpha therapy. J Rheumatol. 2009. 36:2416–2420.

16. Kim YJ, Bae SC, Sung YK, Kim TH, Jun JB, Yoo DH, Kim TY, Sohn JH, Lee HS. Possible reactivation of potential hepatitis B virus occult infection by tumor necrosis factor-alpha blocker in the treatment of rheumatic diseases. J Rheumatol. 2010. 37:346–350.

17. Charpin C, Guis S, Colson P, Borentain P, Mattéi JP, Alcaraz P, Balandraud N, Thomachot B, Roudier J, Gérolami R. Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients. Arthritis Res Ther. 2009. 11:R179.

18. Vassilopoulos D, Apostolopoulou A, Hadziyannis E, Papatheodoridis GV, Manolakopoulos S, Koskinas J, Manesis EK, Archimandritis AI. Long-term safety of anti-TNF treatment in patients with rheumatic diseases and chronic or resolved hepatitis B virus infection. Ann Rheum Dis. 2010. 69:1352–1355.

19. Setoguchi S, Solomon DH, Weinblatt ME, Katz JN, Avorn J, Glynn RJ, Cook EF, Carney G, Schneeweiss S. Tumor necrosis factor α antagonist use and cancer in patients with rheumatoid arthritis. Arthritis Rheum. 2006. 54:2757–2764.

20. Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007. 56:2886–2895.

21. Smitten AL, Simon TA, Hochberg MC, Suissa S. A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther. 2008. 10:R45.

22. Genovese MC, Cohen S, Moreland L, Lium D, Robbins S, Newmark R, Bekker P. 20000223 Study Group. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum. 2004. 50:1412–1419.

23. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R. OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008. 371:987–997.

24. Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008. 67:1516–1523.

25. Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Murata N, van der Heijde D, Kishimoto T. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis. 2007. 66:1162–1167.

26. Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Li T, Ge Z, Becker JC, Westhovens R. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006. 144:865–876.

27. Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, Birbara C, Box J, Natarajan K, Nuamah I, Li T, Aranda R, Hagerty DT, Dougados M. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor-alpha inhibition. N Engl J Med. 2005. 353:1114–1123.

28. Maxwell L, Singh JA. Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009. (4):CD007277.

29. Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC. REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006. 54:2793–2806.

30. Keystone E, Emery P, Peterfy CG, Tak PP, Cohen S, Genovese MC, Dougados M, Burmester GR, Greenwald M, Kvien TK, Williams S, Hagerty D, Cravets MW, Shaw T. Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies. Ann Rheum Dis. 2009. 68:216–221.

31. Finckh A, Ciurea A, Brulhart L, Kyburz D, Möller B, Dehler S, Revaz S, Dudler J, Gabay C. Physicians of the Swiss Clinical Quality Management Program for Rheumatoid Arthritis. B cell depletion may be more effective than switching to an alternative anti-tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti-tumor necrosis factor agents. Arthritis Rheum. 2007. 56:1417–1423.

32. Chatzidionysiou K, Carli CC, Van Vollenhoven RF. Rituximab versus anti-TNF in patients who previously failed one or more anti-TNFs in an observational cohort: The SARASTRA study (Abstract). Presented at the 2009 EULAR scientific meeting. Stockholm, Sweden.

33. Keystone E, Fleischmann R, Emery P, Furst DE, van Vollenhoven R, Bathon J, Dougados M, Baldassare A, Ferraccioli G, Chubick A, Udell J, Cravets MW, Agarwal S, Cooper S, Magrini F. Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: an open-label extension analysis. Arthritis Rheum. 2007. 56:3896–3908.

34. Salliot C, Dougados M, Gossec L. Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann Rheum Dis. 2009. 68:25–32.

35. Fleischmann RM. Progressive multifocal leukoencephalopathy following rituximab treatment in a patient with rheumatoid arthritis. Arthritis Rheum. 2009. 60:3225–3228.

36. Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, Laubach J, Bawn SD, Gordon LI, Winter JN, Furman RR, Vose JM, Zelenetz AD, Mamtani R, Raisch DW, Dorshimer GW, Rosen ST, Muro K, Gottardi-Littell NR, Talley RL, Sartor O, Green D, Major EO, Bennett CL. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood. 2009. 113:4834–4840.

37. Accessed 2010-7-30. http://www.gsk.com/media/pressreleases/2009/2009_us_ pressrelease_10047.htm.

38. Accessed 2010-7-30. http://www.roche.com/media/media_releases/med-cor-2010-03-08.htm.

39. Cohen S, Fleischmann R. Kinase inhibitors: a new approach to rheumatoid arthritis treatment. Curr Opin Rheumatol. 2010. 22:330–335.

40. Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, Krishnaswami S, Burgos-Vargas R, Wilkinson B, Zerbini CA, Zwillich SH. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP- 690,550 versus placebo. Arthritis Rheum. 2009. 60:1895–1905.

41. Damjanov N, Kauffman RS, Spencer-Green GT. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009. 60:1232–1241.

42. Weinblatt ME, Kavanaugh A, Burgos-Vargas R, Dikranian AH, Medrano-Ramirez G, Morales-Torres JL, Murphy FT, Musser TK, Straniero N, Vicente-Gonzales AV, Grossbard E. Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial. Arthritis Rheum. 2008. 58:3309–3318.

TOOLS

Similar articles