Approval Status: Approved May 2017
Specific Treatments: active rheumatoid arthritis
Kevzara (sarilumab) is an interleukin-6 (IL-6) receptor antagonist.
Kevzara is specifically indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).
Kevzara is supplied as a solution for subcutaneous injection. Kevzara may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs. The recommended dosage of Kevzara is 200 mg once every two weeks, administered as a subcutaneous injection.
The FDA approval of Kevzara was based on two randomized, double-blind, placebo controlled multicenter studies (Study 1 and Study 2) in patients older than 18 years with moderately to severely active rheumatoid arthritis (RA) diagnosed according to American College of Rheumatology (ACR) criteria. Study 1 evaluated 1197 patients with moderately to severely active rheumatoid arthritis who had inadequate clinical response to methotrexate (MTX). Patients received subcutaneous Kevzara 200 mg, Kevzara 150 mg, or placebo every two weeks with concomitant MTX. After Week 16 in Study 1, patients with an inadequate response could have been rescued with Kevzara 200 mg every two weeks.
Study 2 evaluated 546 patients with moderately to severely active rheumatoid arthritis who had an inadequate clinical response or were intolerant to one or more TNF-α antagonists. Patients received subcutaneous Kevzara 200 mg, Kevzara150 mg, or placebo every two weeks with concomitant conventional DMARD(s) (MTX, sulfasalazine, leflunomide, and/or hydroxychloroquine). After Week 12 in Study 2, patients with an inadequate response could have been rescued with Kevzara 200 mg every two weeks. In Studies 1 and 2, the primary endpoint was the proportion of patients who achieved an ACR20 response at Week 24. In both studies, patients treated with either 200 mg or 150 mg of Kevzara every two weeks + MTX/DMARD had higher ACR20, ACR50, and ACR70 response rates versus placebo + MTX/DMARD-treated patients at Week 24. The ACR20 response at Week 24 for placebo, Kevzara 150mg and Kevzara 200mg, respectively,was as follows: Study 1: 33.4%, 58.0% and 66.4%. Study 2: 33.7%, 55.8% and 60.9%.
Adverse effects associated with the use of Kevzara may include, but are not limited to, the following:
- increased ALT
- injection site erythema
- upper respiratory infections
- urinary tract infections
Kevzara come with a Black Box warning of the potential for serious infections leading to hospitalization or death including bacterial, viral, invasive fungal, and other opportunistic infections in patients receiving Kevzara.
Mechanism of Action
Kevzara (sarilumab) is an interleukin-6 (IL-6) receptor antagonist. 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.
For additional information regarding Kevzara or rheumatoid arthritis, please visit https://www.kevzara.com/