Skip to main content
SpringerLink
Log in

Sarilumab: A Review in Moderate to Severe Rheumatoid Arthritis

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Sarilumab (Kevzara®), a monoclonal antibody against the interleukin-6 (IL-6) receptor, is approved in various countries, including the USA, those of the EU, and Japan, as a subcutaneous treatment administered every 2 weeks for moderately to severely active rheumatoid arthritis (RA) in adults who have responded inadequately to, or are intolerant of, one or more DMARDs. In placebo-controlled trials, sarilumab improved the signs and symptoms of RA, as well as physical function and health-related quality-of-life (HR-QOL), when administered in combination with conventional synthetic DMARD (csDMARD) therapy in patients with an inadequate response to methotrexate or an inadequate response to, or intolerance of, at least one tumour necrosis factor (TNF) inhibitor; benefits were sustained over ≤ 3 years’ therapy in an open-label extension. Sarilumab plus methotrexate inhibited the progression of structural damage in patients who had inadequately responded to methotrexate. As monotherapy in patients who were inappropriate for continued treatment with methotrexate, sarilumab was more effective than adalimumab in reducing the signs and symptoms of RA and improving physical function. The safety profile of sarilumab was consistent with the anticipated effects of IL-6 inhibition. In the minority of patients who tested positive for anti-drug antibodies (ADAs), ADAs did not impact efficacy or increase adverse reactions. Thus, sarilumab extends the available treatment options for adults with moderately to severely active RA who have responded inadequately to, or are intolerant of, at least one DMARD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Raimondo MG, Biggioggero M, Crotti C, et al. Profile of sarilumab and its potential in the treatment of rheumatoid arthritis. Drug Des Dev Ther. 2017;11:1593–603.

    Article  CAS  Google Scholar 

  2. Smolen JS, Landewe R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960–77.

    Article  PubMed  Google Scholar 

  3. Singh JA, Saag KG, Bridges SLJ, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1–26.

    Article  PubMed  Google Scholar 

  4. Marchesoni A, Zaccara E, Gorla R, et al. TNF-α antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice. Ann N Y Acad Sci. 2009;1173(1):837–46.

    Article  PubMed  CAS  Google Scholar 

  5. Srirangan S, Choy CH. The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskel Dis. 2010;2(5):247–56.

    Article  CAS  Google Scholar 

  6. Regeneron Pharmaceuticals Inc., Sanofi-Aventis U.S. LLC. Prescribing information for Kevzara® (sarilumab) injection, for subcutaneous use. 2017. http://products.sanofi.us/. Accessed 29 May 2018.

  7. European Medicines Agency. Kevzara: summary of product characteristics 2017. http://www.ema.europa.eu/. Accessed 29 May 2018.

  8. Potocky T, Rafique A, Fairhurst J, et al. Evaluation of the binding kinetics and functional bioassay activity of sarilumab and tocilizumab to the human il-6 receptor alpha (il-6rα) [abstract no. ICW-C15-3]. Mod Rheumatol. 2016;26(Suppl):S69–70.

    Google Scholar 

  9. European Medicines Agency. Kevzara: CHMP assessment report. 2017. http://www.ema.europa.eu/. Accessed 29 May 2018.

  10. Dougados M, Choy EH, Kameda H, et al. IL-6R blockade with sarilumab plus methotrexate results in changes in clinical and laboratory parameters associated with chronic inflammation in patients with moderate-to-severe RA in a phase 3 study [abstract no. 2761]. Arthritis Rheumatol. 2015;67(Suppl 10):3336–8.

    Google Scholar 

  11. Gabay C, Msihid J, Daskalakis N, et al. Effect of sarilumab on circulating biomarkers of bone and joint destruction in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors [abstract no. 2615]. Arthritis Rheumatol. 2016;68(Suppl 10):2615.

    Google Scholar 

  12. Gabay C, Msihid J, Paccard C, et al. Sarilumab significantly suppresses circulating biomarkers of bone resorption and cardiovascular risk compared with adalimumab: biomarker analysis from the phase 3 MONARCH study [abstract no. FRI0227]. Ann Rheum Dis. 2017;76(Suppl 2):570.

    Google Scholar 

  13. Emery P, Rondon J, Garg A, et al. Safety and tolerability of subcutaneous sarilumab compared to intravenous tocilizumab in patients with RA [abstract no. 971]. Arthritis Rheumatol. 2015;67(Suppl 10):1268–9.

    Google Scholar 

  14. Kovalenko P, Paccaly A, Boyapati A, et al. Pharmacodynamic (PD) model of neutrophil margination to describe transient effect of sarilumab on absolute neutrophil count (ANC) in patients with rheumatoid arthritis (RA) after single-dose administration [abstract no. 7284 and poster III-58]. In: Annual meeting of the population approach group in Europe. 2017.

  15. Boyapati A, Msihid J, Fiore S, et al. Sarilumab plus methotrexate suppresses circulating biomarkers of bone resorption and synovial damage in patients with rheumatoid arthritis and inadequate response to methotrexate: a biomarker study of MOBILITY. Arthritis Res Ther. 2016;18(1):225.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840–7.

    Article  PubMed  CAS  Google Scholar 

  17. Xu C, Su Y, Paccaly A, et al. Population pharmacokinetics of sarilumab in patients with rheumatoid arthritis [abstract no. 7283]. In: Annual meeting of the population approach group in Europe. 2017.

  18. Lee EB, Daskalakis N, Xu C, et al. Disease-drug interaction of sarilumab and simvastatin in patients with rheumatoid arthritis. Clin Pharmacokinet. 2017;56(6):607–15.

    Article  PubMed  CAS  Google Scholar 

  19. Fleischmann R, van Adelsberg J, Lin Y, et al. Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2017;69(2):277–90.

    Article  PubMed  CAS  Google Scholar 

  20. Genovese MC, Fleischmann R, Kivitz AJ, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a phase III study. Arthritis Rheumatol. 2015;67(6):1424–37.

    Article  PubMed  CAS  Google Scholar 

  21. Sanofi. A study assessing the efficacy and safety of sarilumab added to MTX in Japanese patients with moderately to severely active rheumatoid arthritis (SARIL-RA-KAKEHASI) [ClinicalTrials.gov identifier NCT02293902] US National Institutes of Health, ClinicalTrials.gov. 2017. http://www.clinicaltrials.gov/. Accessed 29 May 2018.

  22. Sanofi. Long term evaluation of sarilumab in rheumatoid arthritis patients (SARIL-RA-EXTEND) [ClinicalTrials.gov identifier NCT01146652] US National Institutes of Health, ClinicalTrials.gov. 2017. http://clinicaltrials.gov/. Accessed 29 May 2018.

  23. Burmester GR, Fiore S, Hu C-C, et al. Efficacy and safety of switching from adalimumab to sarilumab in an open-label extension of a phase 3 monotherapy trial in patients with active rheumatoid arthritis [abstract no. 2482]. Arthritis Rheumatol. 2017;69(Suppl 10):2482.

    Google Scholar 

  24. Burmester GR, Lin Y, Mangan EK, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy in patients with active rheumatoid arthritis in the phase 3 MONARCH study, including subpopulations [abstract no. SAT0202]. Ann Rheum Dis. 2017;76(Suppl 2):849.

    Google Scholar 

  25. Emery P, van Hoogstraten H, Jayawardena S, et al. Efficacy of sarilumab in patients with rheumatoid arthritis who previously received sarilumab or tocilizumab [abstract no. 2468]. Arthritis Rheumatol. 2017;69(Suppl 10):2468.

    Google Scholar 

  26. Fleischmann R, Hrycaj P, van Hoogstraten H, et al. Sarilumab dose reduction in an open-label extension study in RA patients with inadequate response to TNF inhibitors [abstract no. SAT0212]. Ann Rheum Dis. 2017;76(Suppl 2):853.

    Google Scholar 

  27. Fleischmann R, Mangan EK, van Adelsberg J, et al. Onset of action of sarilumab in patients with rheumatoid arthritis in 2 phase 3 studies [abstract no. SAT0180]. Ann Rheum Dis. 2016;75(Suppl 2):733.

    Article  Google Scholar 

  28. Genovese M, Fleischmann R, Mangan E, et al. Efficacy and safety of sarilumab in subgroups of patients with rheumatoid arthritis from 2 phase 3 studies [abstract no. 1632]. Arthritis Rheumatol. 2016;68(Suppl 10):1632.

    Google Scholar 

  29. Genovese MC, Fay J, Parrino J, et al. Sarilumab dose reduction in an open-label extension study in RA patients [abstract no. 1631]. Arthritis Rheumatol. 2016;68(Suppl 10):1631.

    Google Scholar 

  30. Tanaka Y, Sato M, Sumi M, et al. Efficacy of sarilumab, human anti–IL-6 receptor monoclonal antibody in KAKEHASI study, phase 3 trial for Japanese rheumatoid arthritis patients [abstract no. W13-2]. Mod Rheumatol. 2017;27(Suppl):S97.

    Google Scholar 

  31. van der Heijde D, van Adelsberg J, van Hoogstraten H, et al. Clinical and radiographic outcomes after 3 years of sarilumab in patients with rheumatoid arthritis [abstract no. 1633]. Arthritis Rheumatol. 2016;68(Suppl 10):1633.

    Google Scholar 

  32. Sanofi, Regeneron. Human anti-IL-6 receptor monoclonal antibody: Kevzara® subcutaneous injection (150 mg and 200 mg) 2017. http://www.pmda.go.jp/. Accessed 29 May 2018.

  33. Huizinga TW, Fleischmann RM, Jasson M, et al. Sarilumab, a fully human monoclonal antibody against IL-6Ralpha in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014;73(9):1626–34.

    Article  PubMed  CAS  Google Scholar 

  34. Strand V, Kosinski M, Chen CI, et al. Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial. Arthritis Res Ther. 2016;18:198.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Strand V, Reaney M, Chen CI, et al. Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors. RMD Open. 2017;3(1):e000416.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Genovese MC, van Adelsberg J, Fan C, et al. Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes. Rheumatology (Oxford). 2018. https://doi.org/10.1093/rheumatology/key121.

    Article  Google Scholar 

  37. Kameda H, Sato M, Sumi M, et al. Safety of sarilumab, a novel human anti–IL-6 receptor monoclonal antibody: safety outcome at 24 weeks in placebo-controlled double-blind study for Japanese rheumatoid arthritis patients (KAKEHASI study) [abstract no. W13-3]. Mod Rheumatol. 2017;27(Suppl):S97.

    Google Scholar 

  38. American College of Rheumatology. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Appendix 5: executive summary. 2015. http://www.rheumatology.org/. Accessed 29 May 2018.

  39. 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;66:1162–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Wright HL, Cross AL, Edwards SW, et al. Effects of IL-6 and IL-6 blockade on neutrophil function in vitro and in vivo. Rheumatology (Oxford). 2014;53(7):1321–31.

    Article  CAS  Google Scholar 

  41. Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Clinical response to adalimumab: the relationship with anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):921–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. European Medicines Agency. RoActemra 20 mg/ml concentrate for solution for infusion: summary of product characteristics. 2017. http://www.ema.europa.eu/. Accessed 29 May 2018.

  43. June RR, Olsen NJ. Room for more IL-6 blockade? Sarilumab for the treatment of rheumatoid arthritis. Expert Opin Biol Ther. 2016;16(10):1303–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Taylor PC, Moore A, Vasilescu R, et al. A structured literature review of the burden of illness and unmet needs in patients with rheumatoid arthritis: a current perspective. Rheumatol Int. 2016;36:685–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Fournier M, Chen C-I, Kuznik A, et al. Sarilumab for the treatment of active, moderate-to-severe rheumatoid arthritis (RA): an analysis of cost per effectively treated patient [abstract no. 2457]. Arthritis Rheumatol. 2017;69(Suppl 10):2457.

    Google Scholar 

  46. Rischin A, Östör AJK. Update on biosimilars in rheumatology. Immunopharmacology. 2017;25:177–84.

    Google Scholar 

Download references

Acknowledgements

During the peer review process, the manufacturer of sarilumab was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Yvette N. Lamb & Emma D. Deeks

Authors
  1. Yvette N. Lamb
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emma D. Deeks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yvette N. Lamb.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Yvette Lamb and Emma Deeks are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: L. R. Espinoza, Section of Rheumatology, Louisiana State University Health Sciences Center, New Orleans, LA, USA; Y. Matsukawa, Department of Internal Medicine, Tsurumi University School of Dental Medicine, Yokohama, Japan; M. J. Puszczewicz, Department of Rheumatology and Internal Medicine, Poznań University of Medical Sciences, Poznań, Poland; R. Westhovens, Division of Rheumatology, University Hospitals, KU Leuven, Leuven, Belgium.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lamb, Y.N., Deeks, E.D. Sarilumab: A Review in Moderate to Severe Rheumatoid Arthritis. Drugs 78, 929–940 (2018). https://doi.org/10.1007/s40265-018-0929-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-018-0929-z

Search

Navigation