Sarilumab, sold under the brand name Kevzara, is a human

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

medication against the interleukin-6

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

. Regeneron Pharmaceuticals and

Sanofi Sanofi S.A. is a French Multinational corporation, multinational pharmaceutical and healthcare company headquartered in Paris, France. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 200 ...

developed the drug for the treatment of

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

(RA), for which it received US FDA approval on 22 May 2017 and

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

approval on 23 June 2017. Development in

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis from the disease spectrum of axial spondyloarthritis. It is characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. With AS, eye and bow ...

has been suspended after the drug failed to show clinical benefit over

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

in a phase II trial.

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. It can be used alone or in combination with

or other

disease-modifying antirheumatic drug Disease-modifying antirheumatic drugs (DMARDs) comprise a category of otherwise unrelated disease-modifying drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to nonsteroida ...

s (DMARDs). Drugs.com: Sarilumab . Accessed 29 November 2017.

Contraindications

In the European Union, sarilumab is contraindicated in people with active, severe infections. While this is not listed as a contraindication under the US FDA approval, there is a boxed warning that recommends testing for hidden

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

infection before treatment and monitoring for signs of an infection during therapy with sarilumab.

Side effects

The MONARCH trial suggested a significantly higher incidence of

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

in patients receiving 200 mg sarilumab every 2 weeks, compared to patients being treated with

adalimumab Adalimumab, sold under the brand name Humira and others, is a disease-modifying antirheumatic drug and monoclonal antibody used to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn' ...

(13.6% vs 0.5%). However, infection rates were similar between both groups (28.8% vs 27.7%). Other common side effects that occurred in 1% to 10% of patients included

thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...

(low

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

count), infections of the upper respiratory tract and the urinary tract, oral herpes,

hyperlipidaemia Hyperlipidemia is abnormally high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also use ...

, and injection site reactions such as pain or redness.

Clinical trials

Rheumatoid arthritis

On 15 May 2013, both companies announced that 2 new trials were starting (COMPARE and ASCERTAIN) and the first patients had already been enrolled. In June 2015, a phase III trial (with

) for RA reported meeting its three coprimary endpoints. In November 2015, the SARIL-RA-TARGET trial reported good results (meeting both its coprimary end points). In November 2016, the ''MONARCH'' phase III trial comparing sarilimab to

(an anti-TNF) found sarilumab superior at reducing the DAS28-ESR score in patients with RA after 24 weeks. In July 2019, a multi-center trial was launched to study 'Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis.'

History

In October 2016, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) refused approval for marketing as a treatment for rheumatoid arthritis due to

good manufacturing practice Current good manufacturing practices (cGMP) are those conforming to the guidelines recommended by relevant agencies. Those agencies control the authorization and licensing of the manufacture and sale of food and beverages, cosmetics, pharmaceutic ...

(GMP) violations. 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 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...

symptoms. On 7 January 2021, following results from the REMAP-CAP trial,

Tocilizumab Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arter ...

and Sarilumab were added to the UK recommended list for COVID-19 treatment, the

number needed to treat The number needed to treat (NNT) or number needed to treat for an additional beneficial outcome (NNTB) is an epidemiology, epidemiological measure used in communicating the effectiveness of a health-care intervention, typically a treatment with me ...

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 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).- Sivapalasingam S, Lederer DJ, Bhore R, et al. Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19: A Randomized Clinical Trial ublished online ahead of print, 2022 Feb 26 Clin Infect Dis. 2022;ciac153. doi:10.1093/cid/ciac153