Sarilumab

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Sarilumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIL-6R
Names
Trade namesKevzara
Clinical data
Drug classMonoclonal antibody[1]
Main usesRheumatoid arthritis (RA), COVID-19[1][2]
Side effectsLiver problems, low neutrophils, pain at the site of injection, infections[1]
Pregnancy
category
  • US: N (Not classified yet)
Routes of
use
Subcutaneous
Typical dose200 mg[1]
External links
AHFS/Drugs.comMonograph
US NLMSarilumab
MedlinePlusa617032
Legal
License data
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Pharmacokinetics
Bioavailability80%
MetabolismLikely proteases
Elimination half-life8-10 days (concentration dependant)[3]
Chemical and physical data
FormulaC6388H9918N1718O1998S44
Molar mass144164.28 g·mol−1

Sarilumab, sold under the brand name Kevzara, is a medication used to treat rheumatoid arthritis (RA).[1] It is used for moderate to severe disease when other treatments have not worked.[1] It may also may be used for severe COVID-19 when tocilizumab is not available.[2] It is used by injection under the skin.[1]

The most common side effect is infection.[3] Other side effects may include low neutrophils, low platelets, abnormal lipids, liver problems, allergic reactions, and cancer.[3][4] Pain may occur at the site of injection.[1] It is a monoclonal antibody which attaches to and blocks the interleukin-6 receptor.[1]

Sarilumab was approved for medical use in the United States and Europe in 2017.[4][1] In the United States it costs about 7,700 USD per month as of 2021.[5] In the United Kingdom this amount costs the NHS about £1800.[6] In Canada the monthly cost is about 1,500 CAD as of 2017.[7]

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.[8] It can be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs).[1]

COVID-19

A study of 420 patients was halted in September 2020, due to lack of demonstrated effectiveness in treating COVID-19 symptoms.[9]

On January 7, 2021, following a 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 people's recovery and reducing the length of time in intensive care by about a week.[10]

Dosage

It is typically use at a dose of 200 mg every two weeks.[1]

Blood monitoring is recommended before starting treatment and a month or two afterwards.[3][4] Further testing is than recommended every 3 months.[4]

For COVID19 it is used as a single dose of 400 mg in 100 ml of normal saline over 1 hour.[11]

Contraindications

In the European Union, sarilumab is contraindicated in people with active, severe infections.[1] 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.[12]

Side effects

There may be a higher rate of neutropenia in people receiving 200 mg sarilumab every 2 weeks, compared to people being treated with adalimumab (14% vs 0.5%). However, infection rates were similar between both groups (29% vs 28%).[13]

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

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.[13] The drug was eventually approved by the FDA on 22 May 2017.

Research

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.[14]

In June 2015, a phase III trial (with methotrexate) for RA reported meeting its three coprimary endpoints.[15]

In November 2015, the SARIL-RA-TARGET trial reported good results (meeting both its coprimary end points).[16]

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.[13]

In July 2019, a multi-center trial was launched to study 'Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis.' [17]

Ankylosing spondylitis

Development in ankylosing spondylitis has been suspended after the drug failed to show clinical benefit over methotrexate in a phase II trial.[18]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 "Kevzara". Archived from the original on 13 September 2021. Retrieved 11 October 2021.
  2. 2.0 2.1 "Clinical Management Summary". COVID-19 Treatment Guidelines. Archived from the original on 5 November 2021. Retrieved 19 January 2022.
  3. 3.0 3.1 3.2 3.3 Shagroni, T.; Cazares, Ramirez; Kim, J. A.; Furst, Daniel E. (2020). "36. Nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, nonopioid analgesics, & drugs used in gout". In Katzung, Bertram G.; Trevor, Anthony J. (eds.). Basic and Clinical Pharmacology (15th ed.). New York: McGraw-Hill. p. 678. ISBN 978-1-260-45231-0. Archived from the original on 2021-10-10. Retrieved 2021-11-06.
  4. 4.0 4.1 4.2 4.3 "Sarilumab Monograph for Professionals". Drugs.com. Archived from the original on 17 April 2021. Retrieved 11 October 2021.
  5. "Kevzara Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 17 April 2021. Retrieved 11 October 2021.
  6. BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 1161. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
  7. "Sarilumab" (PDF). CADTH. January 2017. Archived (PDF) from the original on 18 October 2018. Retrieved 11 October 2021.
  8. 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.
  9. "Sanofi halts tests of arthritis drug for use as a COVID-19 treatment". Archived from the original on 2021-07-11. Retrieved 2021-07-15.
  10. Roberts, Michelle (2021-01-07). "Two more life-saving Covid drugs discovered". BBC News. Archived from the original on 2021-01-28. Retrieved 2021-01-07.
  11. "Hospitalized Adults: Therapeutic Management". COVID-19 Treatment Guidelines. Archived from the original on 9 January 2022. Retrieved 19 January 2022.
  12. Drugs.com: Sarilumab Monograph. Accessed 2017-11-29.
  13. 13.0 13.1 13.2 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.
  14. "Sanofi and Regeneron Announce Patient Enrollment in Two Phase 3 Trials with Sarilumab in Rheumatoid Arthritis (RA). May 2013" (PDF). Archived (PDF) from the original on 2017-01-19. Retrieved 2021-07-15.
  15. 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.
  16. Walker T. "Sarilumab effective in broad range of RA patients: Study". Formulary Watch. Archived from the original on 21 November 2015.
  17. "More Information". Sarcoidosis Program. Archived from the original on 2019-08-09. Retrieved 2019-08-09.
  18. "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. Archived from the original on September 26, 2017. Retrieved July 15, 2021.

External links

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