New Drug Review: Sarilumab
The FDA approved Kevzara for RA patients.
Sarilumab (Kevzara; Sanofi-Aventis U.S. LLC) has been approved by the FDA for use in patients with moderate-to-severe rheumatoid arthritis who have experienced an inadequate response with, or who did not tolerate DMARDs.
Sarilumab is a human recombinant monoclonal antibody. It binds interleukin-6 (IL-6) receptors and blocks IL-6-mediated signaling. IL-6 is involved with signaling among numerous immune cells as well as synovial and endothelial cells of the joints during the inflammatory processes associated with RA.1
Efficacy
The effectiveness of sarilumab was demonstrated in two randomized double-blind multicenter trials. Participants were at least 18 and had moderate-to-severe RA according to the American College of Rheumatology (ACR) criteria. At baseline, participants had a minimum of eight tender and six swollen joints, and did not tolerate or had demonstrated an inadequate response to previous treatment with methotrexate or a TNF-alpha antagonist.
In both studies, patients received 200 mg or 150 mg of either sarilumab or placebo SQ every 2 weeks in addition to concomitant methotrexate or DMARD therapy. A 20% improvement in the core set of measures for assessing a patient’s signs and symptoms of disease was used as the primary endpoint (ACR20) in both studies. Secondary endpoints included radiographic assessments of joint damage and patient-reported outcomes related difficulties with activities of daily living.
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In both studies, patients on sarilumab plus methotrexate or DMARD treatment experienced higher response rates than those taking placebo plus methotrexate or DMARD treatment. Participants taking sarilumab experienced lower levels of disease activity, significantly less radiographic progression of joint damage, and improvement in physical function from baseline. Those taking sarilumab and concomitant therapy reported larger improvements in their perceptions of health, pain, physical functioning, vitality, social functioning, and mental health compared to those taking placebo in addition to either methotrexate or DMARD therapy. Sarilumab use led to improvements in signs and symptoms associated with RA as well as a reduction in joint damage for some patients.
Safety
Sarilumab has a black box warning.1 Infections leading to hospitalization or death have occurred in patients taking sarilumab. Patients should be tested for latent TB prior to initiation of therapy. If the patient tests positive for TB, treatment for latent TB infection should be started prior to therapy. Patients should be monitored closely for signs and symptoms of any infection.
The most common adverse effects in studies include: serious infections, neutropenia, thrombocytopenia, elevated liver enzymes, and lipid abnormalities requiring monitoring every 4 to 8 weeks upon initiation of sarilumab and every 6 months thereafter.
GI perforation and immunosuppression leading to malignancy are rare, but serious, events have occurred. The risk of GI perforation may be increased in patients with diverticulitis or who are taking corticosteroids or NSAIDS.
Sarilumab is not for use in lactating women.1
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Dosage
Sarilumab is approved for use as a 200-mg dose for subcutaneous administration once every 2 weeks.1 It may be used as monotherapy or in combination with methotrexate or DMARD therapy. The dose of sarilumab may be modified to manage elevations in liver transaminases, neutropenia, or thrombocytopenia. Instructions for dosing modifications are included in the manufacturer’s drug packaging.1
It is not recommended for use in patients with absolute neutrophil count less than 2000/mm3, platelets less than 150,000/mm3 or liver transaminases above 1.5 times the upper limit of normal.
Reference
1. Kevzara [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC. May 2017.
