The introduction of biologic response modifiers has revolutionized treatment approaches in rheumatoid arthritis. The ideal treatment approach to induce remission and minimize joint destruction is yet to be determined, however. The guidelines for the treatment of rheumatoid arthritis were updated in 2008. Evidence published recently may help to guide treatment decisions. In this review, advances in treatment approaches are discussed with added emphasis on the cardiovascular risks to this patient population. New data regarding the biologic response modifiers currently available in the US, abatacept and rituximab, are reviewed. Finally, emerging therapies are introduced, including tocilizumab. Investigational agents in development may provide additional options in the future treatment of rheumatoid arthritis.
Cush JJ, Kavanaugh A., Stein CMRheumatology: Diagnosis and Therapeutics. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
3.
Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum.2008;29:762-84.
4.
Furst DE, Breedveld FC, Kalden JR, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis. 2007;66(suppl 3):iii2-iii22.
5.
Keystone E., Fleischmann R., Emery P., et al. 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.
6.
Edwards JC, Szczepanski L., Szechinski J., et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004 ;350: 2572-2581.
7.
Emery P., Fleischmann R., Filipowicz-Sosnowska A., et al. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum. 2006;54:1390-1400.
8.
Cohen SB, Emery P., Greenwald MW, et al. 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.
9.
Higashida J. , Wun T., Schmidt S., Naguwa SM, Tuscano JMSafety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-alpha treatment. J Rheumatol . 2005;32:2109-2115.
10.
Strand V., Balbir-Gurman A., Pavelka K., et al. Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years. Rheumatology (Oxford). 2006;45:1505-1513.
11.
Genovese MC, Becker JC, Schiff M., et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005 ;353:1114-1123.
12.
Schiff M., Keiserman M., Codding C., et al. Efficacy and safety of abatacept or infliximab versus placebo in ATTEST: a phase III, multicenter, randomized, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2007; [epub ahead of print] doi: 11.1136/ard.2007.080002.
13.
Genant HK, Peterfy CG, Westhovens R., et al. Abatacept inhibits structural damage progression in rheumatoid arthritis: results from the long-term extension of the AIM trial. Ann Rheum Dis. 2007; [epub ahead of print] doi: 10.1136/ard.2007.085084.
14.
Kremer JM, Westhovens R., Leon M., et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med . 2003;349:1907-1915.
15.
Kremer JM, Genant HK, Moreland LW, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006;144:865-876.
16.
Moreland LW , Alten R., Van den Bosch F., 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;46:1470-1479.
17.
Donahue KE, Gartlehner G., Jonas DE, et al. Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis. Ann Intern Med. 2008;148:124-134.
18.
Mader R., Keystone E.Optimizing treatment with biologics. J Rheumatol. Suppl. 2007;80:16-24.
19.
Verschueren P., Esselens G., Westhovens R.Daily practice effectiveness of a step-down treatment in comparison with a tight step-up for early rheumatoid arthritis . Rheumatology (Oxford). 2008;47:59-64.
20.
Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial . Ann Intern Med. 2007;146:406-415.
21.
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.
22.
Mikuls TR, Saag KGComorbidity in rheumatoid arthritis. Rheum Dis Clin North Am. 2001;27:283-303.
23.
Magnano MD, Genovese MCManagement of co-morbidities and general medical conditions in patients with rheumatoid arthritis. Curr Rheumatol Rep. 2005;7:407-415.
24.
Solomon DH, Avorn J., Katz JN, et al. Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheum . 2006;54:3790-3798.
25.
Davis JM 3rd, Maradit Kremers H., Crowson CS, et al. Glucocorticoids and cardiovascular events in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2007;56:820-830.
26.
Suissa S., Bernatsky S., Hudson M.Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum. 2006;55:531-536.
27.
van Halm VP , Nurmohamed MT, Twisk JW, Dijkmans BA, Voskuyl AEDisease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study. Arthritis Res Ther. 2006;8:R151.
28.
Carmona L., Descalzo MA, Perez-Pampin E., et al. All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists . Ann Rheum Dis. 2007;66:880-885.
Humira (adalimumab) [package insert]. North Chicago, IL: Abbott Laboratories; 2008.
32.
Mäki-Petäjä KM, Booth AD, Hall FC, et al. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll Cardiol. 2007 ;50:852-858.
33.
Todd DJ, Costenbader KH, Weinblatt MEAbatacept in the treatment of rheumatoid arthritis. Int J Clin Pract. 2007;61:494-500.
34.
Bruce SP, Boyce EGUpdate on abatacept: a selective costimulation modulator for rheumatoid arthritis . Ann Pharmacother. 2007;41:1153-1162.
35.
Bruce B., Fries JFThe Stanford Health Assessment Questionnaire: a review of its history, issues, progress, and documentation. J Rheumatol. 2003;30:167-178.
36.
Felson DT, Anderson JJ, Boers M., et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38:727-735.
37.
van der Heijde D., van't Hof MA, van Riel PL, et al. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis. 1990;49:916-920.
38.
Kremer J., Westhovens R., Luggen M., et al. Long-term efficacy and safety of abatacept through 3 years of treatment in rheumatoid arthritis patients in the AIM and ATTAIN trials [abstract] . In: American College of Rheumatology Meeting : November 6-11, 2007, Boston, MA. Presentation number 699.
39.
Russell AS, Wallenstein GV, Li T., et al. Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment . Ann Rheum Dis. 2007;66: 189-194.
40.
Berger A., Edelsberg J., Li TT, Maclean JR, Oster G.Dose intensification with infliximab in patients with rheumatoid arthritis . Ann Pharmacother. 2005;39:2021-2025.
41.
Smolen JS, Keystone EC, Emery P., et al. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66:143-150.
42.
Rituxan (rituximab) [package insert]. South San Francisco, CA: Genentech; 2008.
43.
Breedveld F., Agarwal S., Yin M., et al. Rituximab pharmacokinetics in patients with rheumatoid arthritis: B-cell levels do not correlate with clinical response. J Clin Pharmacol. 2007;47:1119-1128.
44.
Schuna AARituximab for the treatment of rheumatoid arthritis. Pharmacotherapy . 2007;27:1702-1710.
45.
Mease PJ, Revicki DA, Szechinski J., et al. Improved health-related quality of life for patients with active rheumatoid arthritis receiving rituximab: Results of the Dose-Ranging Assessment: International Clinical Evaluation of Rituximab in Rheumatoid Arthritis (DANCER) Trial. J Rheumatol. 2008;35:20-30.
46.
Assous N., Gossec L., Dieude P., et al. Rituximab therapy in rheumatoid arthritis in daily practice . J Rheumatol. 2008;35:31-34.
47.
Arkfeld DGThe potential utility of B cell-directed biologic therapy in autoimmune diseases . Rheumatol Int. 2008;28:205-215.
48.
Finckh A., Ciurea A., Brulhart L., et al. 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.
49.
Nishimoto N. , Kishimoto T., Yoshizaki K.Anti-interleukin 6 receptor antibody treatment in rheumatic disease. Ann Rheum Dis. 2000;59(suppl 1):i21-i27.
50.
Ohsugi Y.Recent advances in immunopathophysiology of interleukin-6: an innovative therapeutic drug, tocilizumab (recombinant humanized anti-human interleukin-6 receptor antibody), unveils the mysterious etiology of immune-mediated inflammatory diseases. Biol Pharm Bull. 2007;30:2001-2006.
Nishimoto N. , Yoshizaki K., Miyasaka N., et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004;50: 1761-1769.
53.
Maini RN, Taylor PC, Szechinski J., et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006;54: 2817-2829.
54.
Nishimoto N. , Hashimoto J., Miyasaka N., et al. 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.
55.
Genovese M., Kaine J., Lowenstein M., et al. Ocrelizumab, a novel humanized anti-CD20 antibody: week 72 results from a phase I/II clinical trial in patients with rheumatoid arthritis [abstract] . In: American College of Rheumatology Annual Meeting ; November 6-11, 2007, Boston, MA. Presentation number 695.
56.
Ostergaard M. , Baslund B., Rigby W., et al. Ofatumumab, a human CD20 monoclonal antibody, in the treatment of rheumatoid arthritis: early results from an ongoing, double-blind, randomized, placebo-controlled clinical trial [abstract] . In: American College of Rheumatology Annual Meeting ; November 6-11, 2007, Boston, MA. Presentation number 2086.
57.
Munafo A., Priestley A., Nestorov I., Visich J., Rogge M.Safety, pharmacokinetics and pharmacodynamics of atacicept in healthy volunteers . Eur J Clin Pharmacol. 2007;63:647-656.
58.
Tak PP, Thurlings RM, Rossier C., et al. Atacicept in patients with rheumatoid arthritis: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating, single- and repeated-dose study. Arthritis Rheum. 2008;58:61-72.
