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 antibodies ca ...

medication against the

interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...

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

Regeneron Pharmaceuticals Regeneron Pharmaceuticals, Inc. is an American biotechnology company headquartered in Westchester County, New York. The company was founded in 1988. Originally focused on neurotrophic factors and their regenerative capabilities, giving rise to i ...

and

Sanofi Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

developed the drug for the treatment of

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

(RA), for which it received US

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

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 medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

approval on 23 June 2017. Development in

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hip ...

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

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

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 nonsteroidal ...

s (DMARDs). Drugs.com: Sarilumab . Accessed 2017-11-29.

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 In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that it ...

that recommends testing for hidden

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

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, among others, is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativ ...

(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 Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

(low

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

count), infections of the

upper respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...

and the

urinary tract The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, con ...

, oral herpes,

hyperlipidaemia Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...

, and reactions at the injection site.

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

-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 respon ...

(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, pharmaceutica ...

(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 a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...

symptoms. On January 7, 2021, following a 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, a severe form of arthritis in children, and COVID19. It is a hu ...

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 epidemiological measure used in communicating the effectiveness of a health-care intervention, typically a treatment with medication. The ...

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

References

External links

* {{Portal bar , Medicine Monoclonal antibodies Immunosuppressants Sanofi Disease-modifying antirheumatic drugs