Sarilumab

Sarilumab

Sarilumab

Human monoclonal antibody medication

Sarilumab, sold under the brand name Kevzara, is a human monoclonal antibody medication against the interleukin-6 receptor.[4] Regeneron Pharmaceuticals and Sanofi developed the drug for the treatment of rheumatoid arthritis (RA), for which it received US FDA approval on 22 May 2017 and European Medicines Agency approval on 23 June 2017.[5]

Quick Facts Monoclonal antibody, Type ...

Development in ankylosing spondylitis has been suspended after the drug failed to show clinical benefit over methotrexate in a phase II trial.[6]

Medical uses

Sarilumab is used for the treatment of moderately to severely active rheumatoid arthritis in people who have not responded to, or did not tolerate, more conventional treatments.[7] It can be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs).[8][9]

Contraindications

In the European Union, sarilumab is contraindicated in people with active, severe infections.[8] While this is not listed as a contraindication under the US FDA approval, there is a boxed warning that recommends testing for hidden tuberculosis infection before treatment and monitoring for signs of an infection during therapy with sarilumab.[9]

Side effects

The MONARCH trial suggested a significantly higher incidence of neutropenia in patients receiving 200 mg sarilumab every 2 weeks, compared to patients being treated with adalimumab (13.6% vs 0.5%). However, infection rates were similar between both groups (28.8% vs 27.7%).[10]

Other common side effects that occurred in 1% to 10% of patients included thrombocytopenia (low platelet count), infections of the upper respiratory tract and the urinary tract, oral herpes, hyperlipidaemia, and injection site reactions such as pain or redness.[8]

Clinical trials

Rheumatoid arthritis

On May 15, 2013, both companies announced that 2 new trials were starting (COMPARE and ASCERTAIN) and the first patients had already been enrolled.[11]

In June 2015, a phase III trial (with methotrexate) for RA reported meeting its three coprimary endpoints.[12]

In November 2015, the SARIL-RA-TARGET trial reported good results (meeting both its coprimary end points).[13]

In November 2016, the MONARCH phase III trial comparing sarilimab to adalimumab (an anti-TNF) found sarilumab superior at reducing the DAS28-ESR score in patients with RA after 24 weeks.[10]

In July 2019, a multi-center trial was launched to study 'Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis.' [14]

History

In October 2016, the U.S. Food and Drug Administration (FDA) refused approval for marketing as a treatment for rheumatoid arthritis due to good manufacturing practice (GMP) violations.[10] The drug was eventually approved by the FDA on 22 May 2017.

Research

COVID-19

A study of 420 patients was halted in September 2020, due to lack of demonstrated effectiveness in treating COVID-19 symptoms.[15]

On January 7, 2021, following results from the REMAP-CAP trial, Tocilizumab and Sarilumab were added to the UK recommended list for COVID-19 treatment, the number needed to treat is 12, meaning for every 12 intensive care unit patients treated 1 additional person survives compared to treatment as normal, also speeding up patients' recovery and reducing the length of time that critically-ill patients need to spend in intensive care by about a week [16]

Tocilizumab seems to be more beneficial, whereas the clinical efficacy of Sarilumab has not been established as data on decreased mortality was often not significant. The number of trials did not allow for the identification of a specific patient subset that benefits the most from Sarilumab treatment, yet (May 2022).[17][18]

References

  1. [1]
    "Arthritis". Health Canada. 8 May 2018. Retrieved 13 April 2024.
  2. [2]
    "Regulatory Decision Summary for Kevzara". Drug and Health Products Portal. 12 January 2017. Retrieved 13 April 2024.
  3. [3]
    "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  4. [4]
    "Statement On A Nonproprietary Name Adopted By The USAN Council: Sarilumab" (PDF). ama-assn.org. American Medical Association.
  5. [5]
    "Kevzara: Authorisation details". European Medicines Agency. Retrieved 28 September 2017.
  6. [6]
    "Sanofi and Regeneron Report Positive Phase 2b Trial Results with Sarilumab in Rheumatoid Arthritis". regeneron.com (Press release). Paris & Tarrytown, New York: Regeneron. July 12, 2011.
  7. [7]
    Boyce EG, Rogan EL, Vyas D, Prasad N, Mai Y (Feb 2018). "Sarilumab: Review of a Second IL-6 Receptor Antagonist Indicated for the Treatment of Rheumatoid Arthritis". Annals of Pharmacotherapy. 52 (8): 780–791. doi:10.1177/1060028018761599. PMID 29482351. S2CID 3580054.
  8. [8]
    "Kevzara: EPAR – Product Information" (PDF). European Medicines Agency. 2017-09-26.
  9. [9]
    Drugs.com: Sarilumab Monograph. Accessed 2017-11-29.
  10. [10]
    Burmester GR, Lin Y, Patel R, van Adelsberg J, Mangan EK, Graham NM, et al. (May 2017). "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". Annals of the Rheumatic Diseases. 76 (5): 840–847. doi:10.1136/annrheumdis-2016-210310. PMC 5530335. PMID 27856432.
  11. [11]
    Sanofi and Regeneron Announce Patient Enrollment in Two Phase 3 Trials with Sarilumab in Rheumatoid Arthritis (RA). May 2013
  12. [12]
    Genovese MC, Fleischmann R, Kivitz AJ, Rell-Bakalarska M, Martincova R, Fiore S, et al. (June 2015). "Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study". Arthritis & Rheumatology. 67 (6): 1424–37. doi:10.1002/art.39093. PMID 25733246.
  13. [13]
    Walker T. "Sarilumab effective in broad range of RA patients: Study". Formulary Watch. Archived from the original on 21 November 2015.
  14. [14]
    "More Information". Sarcoidosis Program. Retrieved 2019-08-09.
  15. [15]
    Sanofi halts tests of arthritis drug for use as a COVID-19 treatment
  16. [16]
    Roberts, Michelle (2021-01-07). "Two more life-saving Covid drugs discovered". BBC News. Retrieved 2021-01-07.
  17. [17]
    - Yu SY, Koh DH, Choi M, et al. Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis. Emerg Microbes Infect. 2022;11(1):1154-1165. doi:10.1080/22221751.2022.2059405
  18. [18]
    - Sivapalasingam S, Lederer DJ, Bhore R, et al. Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19: A Randomized Clinical Trial [published online ahead of print, 2022 Feb 26]. Clin Infect Dis. 2022;ciac153. doi:10.1093/cid/ciac153

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