SAR153191
SAR153191 Uses, Dosage, Side Effects, Food Interaction and all others data.
SAR153191 is a fully human anti-IL-6R monoclonal IgG1 antibody that binds to both membrane bound and soluble interleukin 6 (IL-6) receptor forms, thus blocking the cis- and trans-inflammatory signalling cascades of IL-6 . SAR153191 was developped by Sanofi and Regeneron Pharmaceuticals, Inc; it was US FDA-approved in May 2017 and followed by EU approval in June 2017 for the treatment of moderate to severe Rheumatoid Arthritis (RA) in combination with methotrexate . RA is a chronic inflammatory disease characterized by polyarthritis and its treatment has been challenged by the different response in every patient . Subcutaneous administration of SAR153191 has been shown to decrease acute-phase reactant levels and improve in clinical RA symptoms .
Single-dose subcutaneous administration of SAR153191 produced a rapid reduction of CRP levels, leading to normal levels after two weeks of treatment. Peak reduction in the absolute neutrophile count was observed after 3 to 4 days of treatment followed by a recovery to baseline levels. It is observed a decrease in fibrinogen and serum amyloid A as well as an increase in hemoglobin and serum albumin.
| Trade Name | SAR153191 |
| Availability | Prescription only |
| Generic | Sarilumab |
| Sarilumab Other Names | REGN88, SAR153191, Sarilumab |
| Related Drugs | Humira, hydroxychloroquine, Enbrel, Remicade, Rituxan, Orencia |
| Type | |
| Formula | C6388H9918N1718O1998S44 |
| Weight | 150000.0 Da (143900 Da in absence of N-glycosylation in heavy chains (Asn296)) |
| Protein binding | Sarilumab is a covalent heterotetramer composed by two disulfide linked heavy chains covelently linked to a kappa light chain. The heavy chain has a IgG1 constant region with a single N-linked glycosylation site in the Fc portion of the molecule. The complimentarity-determining regions (CDRs) within variable domains of both light and heavy chains combine to form the binding site for IL-6R. As Sarilumab is an IgG1 molecule, it presents Fc-effector function and it is prompt to bind to FcγRI, FcγRIIa, FCγRIIb, FcγRIIIa and FcγRIIIB. However, it does not induce Antibody-Dependant Cell-mediated Cytotoxicity (ADCC) or Complement-Dependant Cytotoxicity (CDC) . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
SAR153191 is a monoclonal antibody used to treat moderate to severe rheumatoid arthritis who have responded poorly or are intolerant of other DMARDs.
Indicated for modere to severe reactive RA in adult patients who are irresponsive, respond inadequately or present intolerance to disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor (TNF) antagonists. It is indicated to be used in combination with methotrexate (MTX) or as a monotherapy when there is intolerance to MTX or MTX administration is inappropriate.
SAR153191 is also used to associated treatment for these conditions: Moderate, active Rheumatoid arthritis, Severe, active Rheumatoid arthritis
How SAR153191 works
SAR153191 is a human recombinant IgG1 antibody that binds to both forms of interleukin 6 receptors (IL-6R), thus inhibiting the IL-6-mediated signaling. IL-6 is known to be a pleiotropic cytokine that activates immune cells (T and B cells), as well as hepatocytes for the release of acute phase proteins like CRP, serum amyloid A and fibrinogen which are biomarkers of RA activity. IL-6 is also found in synovial fluid and plays a major role in the pathological inflammation and joint destruction features of RA. Thus, it is used for the treatment of RA due to its ability to inhibit intra-articular and systemic IL-6 signaling .
Toxicity
Repeat dose exposure has been shown to produce a partially reversible decrease in neutophil count and a reversible decrease in fibrinogen .
Food Interaction
No interactions found.SAR153191 Cholesterol interaction
[Moderate] The use of sarilumab is associate with increases in lipid parameters such as LDL cholesterol, HDL cholesterol and Care should be exercised when using this agent in patients with lipid abnormalities. It is recommended to assess lipid parameters at baseline and parameters approximately 4 to 8 weeks following initiation of treatment, then at approximately 6 months intervals.
SAR153191 Drug Interaction
Major: upadacitinibModerate: everolimusUnknown: antihemophilic factor, sotalol, satralizumab, esomeprazole, levothyroxine, inebilizumab, sildenafil
SAR153191 Disease Interaction
Major: immunizationModerate: infections, tuberculosis, blood disorders, diverticulitis, hepatic impairment, hyperlipidemia, renal dysfunction
Volume of Distribution
In patients with RA, the apparent volume of distribution at steady state was 7.3 L .
Elimination Route
SAR153191 is shown to be well absorbed in RA patients after single SC administration with a maximum of serum concentration presented after 2 to 4 days. For the 150 mg every two weeks dose regimen, the AUC, Cmin and Cmax of sarilumab were 202 ± 120 mg.day/L, 6.35 ± 7.54 mg/L, and 20.0 ± 9.20 mg/L, respectively. For the 200 mg every two weeks dose regimen, the AUC, Cmin and Cmax of sarilumab were 395 ± 207 mg.day/L, 16.5 ± 14.1 mg/L, and 35.6 ± 15.2 mg/L, respectively .
Half Life
The half life will depend on the administered concentration. At 200 mg every 2 weeks, half-life is up to 10 days in patients with RA at steady state. At 150 mg every 2 weeks, half-life is up to 8 days in patients with RA at steady state. After the last steady state dose of 150 mg and 200 mg, the time to reach nondetectable concentration is 28 and 43 days, respectively .
Clearance
SAR153191 is not eliminated via renal or hepatic pathways. RA patients have shown a trend toward higher clearance in presence of anti-sarilumab antibodies [FDA file].
Elimination Route
At high concentrations, SAR153191 is thought to be eliminated predominantly through a non-saturated proteolytic pathway, while at lower concentrations, the elimination will be done by saturable target-mediated elimination .
Innovators Monograph
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