Sarilumab

Indications

Sarilumab is used for: Rheumatoid Arthritis

Adult Dose

Rheumatoid Arthritis Indicated for adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to ?1 disease-modifying antirheumatic drugs (DMARDs) 200 mg SC q2wk May be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs

Child Dose

Renal Dose

Renal impairment Mild-to-moderate: No dose adjustment required Severe: Not studied

Administration

SC Preparation Remove from refrigerator and allow to sit at room temperature for 30 minutes (prefilled syringes) or 60 minutes (prefilled pen) y Visually inspect syringe for particulate matter and discoloration prior to administration Solution should be clear and colorless to pale yellow; do not use if the solution is cloudy, discolored, or contains particles, or if any part of the prefilled syringe appears to be damaged SC Administration Patient may self-inject or the patient's caregiver may administer after properly instructed Instruct patients to inject the full amount in the syringe (1.14 mL), which provides 200 mg or 150 mg Rotate injection sites with each injection; do not inject into skin that is tender, damaged, or has bruises or scars Do not rub the injection site

Contra Indications

Documented hypersensitivity to drug or inactive ingredients

Precautions

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported GI perforations reported in clinical studies, primarily as complications of diverticulitis; GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids Immunosuppression may result in an increased risk of malignancies Hypersensitivity reactions reported Not recommended with active hepatic disease or hepatic impairment

Pregnancy-Lactation

Pregnancy Limited human data in pregnant women are not sufficient to inform drug-associated risk for major birth defects and miscarriage Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed in utero From the animal data, and consistent with the mechanism of action, levels of IgG, in response to antigen challenge, may be reduced in the fetus/infant of treated mothers Lactation Unknown if distributed in human breast milk Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

Avoid coadministering with biological DMARDs (eg, TNF antagonists, IL-1R antagonists, antiCD20 monoclonal antibodies, JAK inhibitors, selective costimulation modulators) because of increased risk for immunosuppression and infection Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections

Side Effects

Side effects of Sarilumab : >10% ALT >ULN to ≤3 x ULN (38-43%) AST >ULN to ≤3 x ULN (27-30%) 1-10% Neutropenia (7-10%) ANC <1000/mm³ (4-6%) Injection site erythema (4-5%) Injection site pruritics (4-5%) Upper respiratory tract infection (3-4%) ALT >3x to 5x ULN (3-4%) Urinary tract infection (3%) Hypertriglyceridemia (1-3%) Leukopenia (0.9-2%) AST >3x to 5x ULN (1%) ALT>5x ULN (0.7-1%) Decreased platelet counts (0.7-1%) <1% ANC <500 /mm³ (0.7%) AST>5x ULN (0.2-0.7%)

Mode of Action

Human monoclonal antibody that binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors IL-6 is produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes (eg, rheumatoid arthritis) IL-6 is a pleiotropic proinflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes, and fibroblasts IL-6 has been shown to be involved in diverse physiological processes (eg, T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute-phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation