Sarilumab

KEVZARA ® is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of: adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. patients who weigh 63 kg or greater with active polyarticular juvenile idiopathic arthritis (pJIA).

Sarilumab 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 a pleiotropic pro-inflammatory 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 such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis.

General Considerations for Administration KEVZARA initiation is not recommended in patients with ANC less than 2,000/mm 3, platelets less than 150,000/mm 3 or liver transaminases above 1.5 times ULN. See Full Prescribing Information (FPI) for complete information. Recommended Dosage in RA The recommended dosage is 200 mg subcutaneously, once every 2 weeks. For RA, KEVZARA may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs. Recommended Dosage in PMR The recommended dosage is 200 mg subcutaneously, once every two weeks in combination with a tapering course of corticosteroids. For PMR, KEVZARA can be used as monotherapy following discontinuation of corticosteroids.

KEVZARA is contraindicated in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.

Boxed warning (risk of serious infections): Patients treated with KEVZARA are at increased risk for developing serious infections that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving KEVZARA. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Avoid use of KEVZARA in patients with an active infection. Serious Infections: Avoid KEVZARA use during an active infection. Neutropenia, Thrombocytopenia, Elevated Liver Enzymes, Lipid Abnormalities: Monitor laboratory parameters. Gastrointestinal (GI) Perforation: Risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Promptly evaluate acute abdominal signs or symptoms. Hypersensitivity reactions. Live vaccines: Avoid use with KEVZARA.

The following serious adverse reactions are described elsewhere in labeling: Serious infections Neutropenia, thrombocytopenia, elevated liver enzymes, lipid abnormalities Gastrointestinal perforation Immunosuppression Hypersensitivity reactions Most common adverse reactions are: Rheumatoid Arthritis (incidence ≥3 %): neutropenia, increased ALT, injection site erythema, upper respiratory infections and urinary tract infections. Polymyalgia Rheumatica (incidence ≥ 5%): neutropenia, leukopenia and injection site pruritus. Polyarticular Juvenile Idiopathic Arthritis: nasopharyngitis, neutropenia, upper respiratory tract infection and injection site erythema.

Use with Other Drugs Population pharmacokinetic analyses did not detect any effect of methotrexate (MTX) on sarilumab clearance. KEVZARA has not been investigated in combination with JAK inhibitors or biological DMARDs such as TNF antagonists.

and Stability Refrigerate at 36°F to 46°F (2°C to 8°C) in original carton to protect from light. Do not freeze. If needed, patients/caregivers may store KEVZARA at room temperature up to 77°F (25°C) up to 14 days in the outer carton. Do not store above 77°F (25°C). After removal from the refrigerator, use KEVZARA within 14 days or discard. Do not shake.