Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-28T11:03:26.118Z Has data issue: false hasContentIssue false
  • English
  • Français

RITUXIMAB AND TOCILIZUMAB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

Published online by Cambridge University Press:  28 July 2014

Nicolás González-Vacarezza ,
Alicia Alemán ,
Graciela González  and
Ana Pérez
Nicolás González-Vacarezza
Affiliation:
Ministry of Public Health and National Institute of Rheumatology
Alicia Alemán
Affiliation:
Ministry of Public Health and National Institute of Rheumatology
Graciela González
Affiliation:
Ministry of Public Health and National Institute of Rheumatology
Ana Pérez
Affiliation:
Ministry of Public Health and National Institute of Rheumatology
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives: The aim of this study was to evaluate the efficacy and safety of rituximab and tocilizumab compared with adalimumab, etanercept, and infliximab, in patients with rheumatoid arthritis not responding to first-line treatment, and to compare the efficacy and safety of rituximab versus tocilizumab in patients not responding to anti-tumor necrosis factor α (anti-TNF) therapy.

Methods: A literature search of randomized controlled trials, controlled clinical trials, and systematic reviews was performed to evaluate efficacy and safety of rituximab and tocilizumab.

Results: Twenty-four RCTs were included in this systematic review with 6,357 participants; 3,450 treated with biological DMARD and 2,907 with standard care. In patients not responding to first-line treatment, rituximab shows lower response rate in at least 50 percent improvement in the American College of Rheumatology criteria (ACR50) and ACR70 compared with etanercept, at 6 months of follow-up. Tocilizumab shows higher ACR70 response rate compared with infliximab, at the same follow-up time. Other results showed no significant differences. Indirect comparisons between rituximab and tocilizumab in patients not responding for at least one anti-TNF, shows higher ACR20 response rate for tocilizumab at 6 months of follow-up. Regarding safety, adalimumab and etanercept were associated with significant fewer withdrawals due to adverse events compared with infliximab.

Conclusions: Considering efficacy, safety, and the availability of 3 anti-TNFs in the National Medicines Formulary (adalimumab, etanercept, and infliximab), it seems appropriate to remove infliximab from the coverage, and introduce tocilizumab for patients not responding for at least one anti-TNF.

Keywords

RituximabTocilizumabRheumatoidArthritis
Type
Assessments
Information
International Journal of Technology Assessment in Health Care , Volume 30 , Issue 3: Theme: Adaptive Approaches to Licensing , July 2014 , pp. 282 - 288
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Patel, AM, Moreland, LW. Interleukin-6 inhibition for treatment of rheumatoid arthritis: A review of tocilizumab therapy. Drug Des Devel Ther. 2010;4:263–278.CrossRefGoogle ScholarPubMed
2. Carmona, L, Cross, M, Williams, B, Lassere, M, March, L. Rheumatoid arthritis. Res Clin Rheumatol. 2010;24:733–745.Google ScholarPubMed
3. Silman, AJ, Pearson, JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4:S265–S272.CrossRefGoogle ScholarPubMed
4. Smolen, JS, Landewé, R, Breedveld, FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69:964–975.CrossRefGoogle ScholarPubMed
5. Arnett, FC, Edworthy, SM, Bloch, DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–324.CrossRefGoogle ScholarPubMed
6. 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.CrossRefGoogle ScholarPubMed
7. Higgins, JP, Thompson, SG, Deeks, JJ, Altman, DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.CrossRefGoogle ScholarPubMed
8. Wells, GA, Sultan, SA, Chen, L, Khan, M, Coyle, D. Indirect treatment comparisson [computer program]. Version 1.0. Ottawa: Canadian Agency for Drugs and Technology in Health; 2009.Google Scholar
9. Wells, GA, Sultan, SA, Chen, L, Khan, M, Coyle, D. Ottawa. Indirect evidence: Indirect treatment comparisons in meta-analysis. Ottawa: Candian Agency for Drugs and Technology in Health; 2009.Google Scholar
10. Navarro-Sarabia, F, Ariza-Ariza, R, Hernandez-Cruz, B, Villanueva, I. Adalimumab for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2005;3:CD005113.Google Scholar
11. Blumenauer, BBTB, Cranney, A, Burls, A, et al. Etanercept for the treatment of rheumatoid arthritis. Cochrane Database Syst Rev. 2003;3:CD004525.Google Scholar
12. Blumenauer, B, Judd, M, Wells, G, et al. Infliximab for the treatment of rheumatoid arthritis. Cochrane Database Syst Rev. 2002;3:CD003785.Google ScholarPubMed
13. Singh, JA, Beg, S, Lopez-Olivo, MA. Tocilizumab for rheumatoid arthritis. Cochrane Database Syst Rev. 2010;7:CD008331.Google Scholar
14. Kremer, JM, Blanco, R, Brzosko, M, et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: Results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum. 2011;63:609–621.CrossRefGoogle ScholarPubMed
15. Weinblatt, ME, Keystone, EC, Furst, DE, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMADA trial. Arthritis Rheum. 2003;48:35–45.CrossRefGoogle ScholarPubMed
16. Schiff, M, Keiserman, M, Codding, C, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: A phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67:1096–1103.CrossRefGoogle ScholarPubMed
17. Breedveld, FC, Weisman, MH, Kavanaugh, AF, et al. 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.CrossRefGoogle Scholar
18. Furst, DE, Schiff, MH, Fleischmann, RM, et al. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: Results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol. 2003;30:2563–2571.Google ScholarPubMed
19. van de Putte, LB, Atkins, C, Malaise, M, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004;63:508–516.CrossRefGoogle Scholar
20. Miyasaka, N, Taneichi, K, Atsumi, T, et al. Clinical investigation in highly disease-affected rheumatoid arthritis patients in Japan with adalimumab applying standard and general evaluation: The CHANGE study. Mod Rheumatol. 2008;18:252–262.CrossRefGoogle ScholarPubMed
21. Combe, B, Codreanu, C, Fiocco, U, et al. Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: A double-blind comparison. Ann Rheum Dis. 2006;65:1357–1362.CrossRefGoogle ScholarPubMed
22. Combe, B, Codreanu, C, Fiocco, U, et al. Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: A double-blind randomised 2-year study. Ann Rheum Dis. 2009;68:1146–1152.CrossRefGoogle Scholar
23. Moreland, LW, Schiff, MH, Baumgartner, SW, et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med. 1999;130:478–486.CrossRefGoogle ScholarPubMed
24. Weinblatt, ME, Kremer, JM, Bankhurst, AD, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999;340:253–259.CrossRefGoogle ScholarPubMed
25. 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 Rheum. 1998;41:1552–1563.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
26. Westhovens, R, Yocum, D, Han, J, et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: A large, randomized, placebo-controlled trial. Arthritis Rheum. 2006;54:1075–1086.CrossRefGoogle ScholarPubMed
27. Maini, R, St Clair, EW, Breedveld, F, et al. 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.CrossRefGoogle ScholarPubMed
28. Lipsky, PE, van der Heijde, DM, St Clair, EW, et al. 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.CrossRefGoogle ScholarPubMed
29. Taylor, PC, Steuer, A, Gruber, J, et al. Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis. Arthritis Rheum. 2004;50:1107–1116.CrossRefGoogle Scholar
30. 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.CrossRefGoogle ScholarPubMed
31. Emery, P, Deodhar, A, Rigby, WF, et al. Efficacy and safety of different doses and retreatment of rituximab: A randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010;69:1629–1635.CrossRefGoogle Scholar
32. Genovese, MC, McKay, JD, Nasonov, EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: The tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008;58:2968–2980.CrossRefGoogle ScholarPubMed
33. 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.CrossRefGoogle ScholarPubMed
34. Smolen, JS, Beaulieu, A, Rubbert-Roth, A, et al. 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.CrossRefGoogle ScholarPubMed
35. 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.CrossRefGoogle Scholar
36. 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.CrossRefGoogle ScholarPubMed
37. Emery, P, Keystone, E, Tony, HP, et al. 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.CrossRefGoogle ScholarPubMed
38. 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.CrossRefGoogle ScholarPubMed
39. Bejarano, V, Quinn, M, Conaghan, PG, et al. Effect of the early use of the anti-tumor necrosis factor adalimumab on the prevention of job loss in patients with early rheumatoid arthritis. Arthritis Rheum. 2008;59:1467–1474.CrossRefGoogle ScholarPubMed
40. Ho-Youn, K, Soo-Kon, L, Yeong Wook, S, et al. A randomized, double-blind, placebo-controlled, phase III study of the human anti-tumor necrosis factor antibody adalimumab administered as subcutaneous injections in Korean rheumatoid arthritis patients treated with methotrexate. Int J Rheum Dis. 2007;10:9–16.Google Scholar
41. Bathon, JM, Martin, RW, Fleischmann, RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586–1593.CrossRefGoogle ScholarPubMed
42. Emery, P, Breedveld, FC, Hall, S, Durez, P, Chang, DJ, Robertson, D, et al. 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.CrossRefGoogle Scholar
43. Klareskog, L, van der Heijde, D, de Jager, JP, et al. 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.CrossRefGoogle ScholarPubMed
44. Quinn, MA, Conaghan, PG, O’Connor, PJ, et al. Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: Results from a twelve-month randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52:27–35.CrossRefGoogle ScholarPubMed
45. St Clair, EW, van der Heijde, DM, Smolen, JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: A randomized, controlled trial. Arthritis Rheum. 2004;50:3432–3443.CrossRefGoogle ScholarPubMed
46. Tak, PP, Rigby, WF, Rubbert-Roth, A, et al. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: The IMAGE trial. Ann Rheum Dis. 2011;70:39–46.CrossRefGoogle ScholarPubMed
47. Mease, PJ, Cohen, S, Gaylis, NB, et al. Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors: Results from the SUNRISE trial. J Rheumatol. 2010;37:917–927.CrossRefGoogle ScholarPubMed
48. Choy, EH, Isenberg, DA, Garrood, T, et al. Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: A randomized, double-blind, placebo-controlled, dose-escalation trial. Arthritis Rheum. 2002;46:3143–3150.CrossRefGoogle ScholarPubMed
49. Jones, G, Sebba, A, Gu, J, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: The AMBITION study. Ann Rheum Dis. 2010;69:88–96.CrossRefGoogle ScholarPubMed
50. Nishimoto, N, Miyasaka, N, Yamamoto, K, et al. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): Significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol. 2009;19:12–19.CrossRefGoogle ScholarPubMed
51. 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.CrossRefGoogle ScholarPubMed
52. Boers, M, Tugwell, P, Felson, DT, et al. World Health Organization and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials. J Rheumatol Suppl. 1994;41:86–89.Google ScholarPubMed
53. Singh, JA, Wells, GA, Christensen, R, et al. Adverse effects of biologics: A network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2:CD008794.Google Scholar
54. Grijalva, CG, Chen, L, Delzell, E, et al. Initiation of tumor necrosis factor-α antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA. 2011;306:2331–2339.Google ScholarPubMed
Supplementary material: File

González-Vacarezza Supplementary Material

Table S1

Download González-Vacarezza Supplementary Material(File)
File 19.6 KB