Biologics in the treatment of rheumatoid arthritis

Czech version

Authors: J. Tomasová Studýnková
Authors‘ workplace: Revmatologický ústav a Revmatologická klinika 1. LF UK, Praha
Published in: Kardiol Rev Int Med 2014, 16(5): 420-425
Category: Internal Medicine

Overview

The last few decades have seen major progress in the treatment of rheumatoid arthritis, mainly thanks to the advances in biotechnology. In addition to the basic, synthetic disease‑ modifying antirheumatic drugs, new generation drugs – biologics – have been used in the treatment of patients suffering from rheumatoid arthritis since 1998. Biologics intervene directly in the pathogenic immune processes leading to disease progression. They were developed through a better understanding of the pathogenesis of inflammation in rheumatoid arthritis, the function of cytokines, and immune system cells. Currently we use biologics for either blocking some of the inflammatory cytokines (anti‑TNF, IL‑1 and IL‑6), or the cellular mechanisms (anti‑CD20, CTLA‑ 4). Their clinical efficacy and ability to practically stop radiographic progression of the disease has been demonstrated in many clinical trials for rheumatoid arthritis. The negative aspects of the treatment include some of the side‑ effects and price.

Keywords:
rheumatoid arthritis – biologics – anti‑TNF therapy – rituximab – abatacept – biosimilars

Sources

1. Alamanos Y, Voulgari PV, Drosos AA. Epidemiology of rheumatic diseases in Greece. J Rheumatol 2004; 8: 1669– 1670. doi: 10.1016/ j.autrev.2004.09.002.

2. Neogi T, Aletaha D, Silman AJ et al. The 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report. Arthritis Rheum 2010; 62: 2582– 2591. doi: 10.1002/ art.27580.

3. Smolen JS, Landewé R, Breedveld FC et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease‑ modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014; 73: 492– 509. doi: 10.1136/ annrheumdis‑ 2013‑ 204573.

4. Smolen J., Aletaha D, Bijlsma JW et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010; 69: 631– 637. doi: 10.1136/ ard.2009.123919.

5. Nam JL, Ramiro S, Gaujoux‑ Viala C et al. Efficacy of biological disease‑ modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2014; 73: 516– 528. doi: 10.1136/ annrheumdis‑ 2013‑ 204577.

6. Smolen JS, Aletaha D, Koeller M et al. New therapies for treatment of rheumatoid arthritis. Lancet 2007; 370: 1861– 1874.

7. Genovese MC, Bathon JM, Martin RW et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two‑year radiographic and clinical outcomes. Arthritis Rheum 2002; 46: 1443– 1450. doi: 10.1002/ art.10308.

8. Emery P, Breedveld FC, Hall S 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. doi: 10.1016/ S0140‑ 6736(08)61000‑ 4.

9. van der Heijde D, Klareskog L, Rodriguez‑ Valverde Vet al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two‑year clinical and radiographic results from the TEMPO study, a double‑blind, randomized trial. Arthritis Rheum 2006; 54: 1063– 1074. doi: 10.1002/ art.21655.0.

10. Smolen JS, Nash P, Durez P et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet 2013; 381: 918– 929. doi: 10.1016/ S0140‑ 6736(12)61811‑ X.

11. Smolen JS, Aletaha D, Bijlsma JW et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010; 69: 631– 637. doi: 10.1136/ ard.2009.123919.

12. Ramiro S, Gaujoux‑ Viala C, Nam JL et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014; 73: 529– 535. doi: 10.1136/ annrheumdis‑ 2013‑ 204575.

13. Carmona L, Abasolo L, Descalzo MA et al. Cancer in patients with rheumatic diseases exposed to TNF antagonists. Semin Arthritis Rheum 2011; 41: 71– 80. doi: 10.1016/ j.semarthrit.2010.08.005.

14. 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. doi: 10.1056/ NEJM200011303432202.

15. 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. doi: 10.1002/ art.21519.

16. Smolen JS, Emery P, Fleischmann R et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet 2014; 383: 321– 332. doi: 10.1016/ s0140‑ 6736(13)61751‑ 1.

17. Keystone EC, Genovese MC, Klareskog L et al. Golimumab, a human antibody to tumour necrosis factor a given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO‑ FORWARD Study. Ann Rheum Dis 2009; 68: 789– 796. doi: 10.1136/ ard.2008.099010.

18. Weinblatt ME, Fleischmann R, Huizinga TW et al. Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study. Rheumatology 2012; 51: 2204– 2214. doi: 10.1093/ rheumatology/ kes150.

19. Smolen JS, Emery P, Ferraccioli GF et al. Certolizumab pegol in rheumatoid arthritis patients with low to moderate activity: the CERTAIN double‑blind, randomised, placebo‑ controlled trial. Ann Rheum Dis 2014. doi: 10.1136/ annrheumdis‑ 2013‑ 204632.

20. Singh JA, Christensen R, Wells GA et al. A network meta‑analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview. CMAJ 2009; 181: 787– 796. doi: 10.1503/ cmaj.091391.

21. Sandborg C, Mellins ED. A new era in the treatment of systemic juvenile idiopathic arthritis. N Engl J Med 2012; 367: 2439– 2440. doi: 10.1056/ NEJMe1212640.

22. 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. doi: 10.1002/ art.23940.

23. 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. doi: 10.1136/ ard.2008.105197.

24. Gabay C, Emery P, van Vollenhoven R et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double‑blind, controlled phase 4 trial. Lancet 2013; 381: 1541– 1550. doi: 10.1016/ S0140‑ 6736(13)60250‑ 0.

25. Dörner T, Burmester GR. The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets. Curr Opin Rheumatol 2003; 15: 246– 252. doi: 10.1097/ 00002281‑ 200305000‑ 00011.

26. Cohen SB, Emery P, Greenwald MW et al. 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. doi: 10.1002/ art.22025.

27. Genovese MC, Covarrubias A, Leon G et al. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum 2011; 63: 2854– 2864. doi: 10.1002/ art.30463.

28. van Vollenhoven RF, Fleischmann R, Cohen S et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 2012; 367: 508– 519. doi: 10.1056/ NEJMoa1112072.

29. Scheinberg MA, Kay J. The advent of biosimilar therapies in rheumatology – “O brave new world”. Nat Rev Rheumatol 2012; 8: 430– 436. doi: 10.1038/ nrrheum.2012.84.

30. Pavelka K, Vencovský J. Doporučení České revmatologické společnosti pro léčbu revmatoidní artritidy. Čes Revmatol 2010; 4: 182– 191.