Drug information of sirukumab

sirukumab

Drug group:

Brand drugs:Plivensia

Plivensia (sirukumab) is a human anti-interleukin-6 monoclonal antibody in development for the treatment of rheumatoid arthritis.
Sirukumab has been used in trials studying the treatment and basic science of Giant Cell Arteritis and Arthritis, Rheumatoid

Drug forms
  • prefilled pen, 1 mL solution with 50 mg sirukumab
  • Prefilled syringe, 1 mL solution with 50 mg sirukumab

Mechanism of effect

interleukin6 inhibitor

Pharmacodynamic

Sirukumab (PLIVENSA) is a human anti-IL-6 immunoglobulin G1 kappa (IgG1) monoclonal antibody (mAb) that binds specifically with high affinity to the cytokine IL-6, preventing IL-6-mediated signalling. Inhibition of the IL-6 pathway in RA has been clinically validated by tocilizumab (ACTEMRA ), a treatment targeting the IL-6 pathway by binding the IL-6 receptor (IL-6R). Recently, another IL-6R antagonist, sarilumab (KEVZARA ), was approved by the Food and Drug Administration (FDA). Sirukumab would be the first inhibitor of IL-6 to be approved by the FDA for the treatment of RA.

Pharmacokinetics

Following SC administration, the time to reach maximum serum concentrations (Tmax) ranged from 3 to 5 days. A single SC administration of 50 mg or 100 mg to healthy patients produced a mean ± standard deviation Cmax of 4.50 ± 1.48 µg/mL and 9.34 ± 3.10 µg/mL, respectively. The mean absolute bioavailability following a single SC dose of sirukumab was approximately 90%. Following repeat SC administrations of sirukumab in patients with RA, trough serum sirukumab concentrations reached steady state by Week 12 with median steady-state trough concentrations in different Phase 3 studies ranging from 1.40 to 1.75 µg/mL and 8.30 to 10.13 µg/mL, respectively, for 50 mg q4w and 100 mg q2w. The mean volume of distribution ranged from 121.3 to 247.7 mL/kg in healthy patients. As a human IgG1κ monoclonal antibody, sirukumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. The mean systemic clearance appeared to be dose independent and ranged from 3.8 to 6.1 mL/day/kg following a single IV administration of sirukumab 0.3 to 10.0 mg/kg. The mean terminal half-life ranged from 15 to 19 days in both healthy patients and RA patients.

Drug indications

artirit rhomatoid

Dosage

The recommended dosage for adult patients with RA is 50 mg every 4 weeks given as a SC injection. The use of sirukumab with other biological DMARDs or targeted small molecules is not recommended. Sirukumab would be available as a solution for injection for SC administration in 2 presentations:  SmartJect® autoinjector/prefilled pen, containing 1 mL solution with 50 mg sirukumab  Prefilled syringe, containing 1 mL solution with 50 mg sirukumab

Drug contraindications

Hypersensitivity to this drug

Alerts

The propensity for direct drug-drug interactions between sirukumab and substrates, inhibitors or inducers of cytochrome P450 enzymes (CYP) and/or drug transporters is low since sirukumab is catabolized by proteolysis at the reticuloendothelial system, which is different from the metabolic pathways via CYPs and transporters for small-molecule drugs.
Therefore, upon initiation or discontinuation of sirukumab, in patients being treated with these types of medicinal products, therapeutic monitoring of effect (eg, warfarin) or drug concentration (eg, cyclosporine, theophylline) should be performed and the individual dose of the drug adjusted as needed

Points of recommendation


These observations suggest that TB screening and initiation of treatment for latent TB prior to initiation of sirukumab provides effective risk mitigation.

Pregnancy level

HAVE NOT BEEN ESTABLISHED


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