Kevzara (sarilumab) - 2 indications

• for the treatment of active rheumatoid arthritis; approved May 2017
• for the treatment of polymyalgia rheumatica; approved February 2023

General Information

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 (RA) who have had an inadequate response or intolerance to one or more disease modifying antirheumatic drugs (DMARDs); 
• for the treatment of adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

Kevzara is supplied as a solution for subcutaneous injection. Scroll down for specific dosing/administration recommendations for each indication.

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. 

Side Effects

Adverse effects associated with the use of Kevzara may include, but are not limited to, the following:

• Neutropenia
• 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.

Indication 1 - for the treatment of active rheumatoid arthritis

approved May 2017

Dosing/Administration

The recommended dosage of Kevzara is 200 mg once every two weeks given as a subcutaneous injection. Kevzara may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs. 

Clinical Trial Results

FDA approval of Kevzara was based on two randomized, double-blind, placebo-controlled multicenter studies (study one and study two) 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 1,197 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 one, patients with an inadequate response could have been rescued with Kevzara 200 mg every two weeks.

Study two 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 two, 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 one: 33.4 percent, 58.0 percent and 66.4 percent. Study two: 33.7percent, 55.8 percent and 60.9 percent. 

Indication 2 - for the treatment of polymyalgia rheumatica

approved February 2023

Dosing/Administration

The recommended dosage of Kevzara is 200 mg once every two weeks given as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids. Kevzara can be used as monotherapy following discontinuation of corticosteroids. 

Clinical Trial Results

FDA approval of Kevzara was based on results from the SAPHYR Phase 3 randomized clinical trial in patients with steroid-resistant active PMR, who flared on ≥7.5 mg/day prednisone or equivalent during taper. In the trial, patients were randomized to receive either Kevzara 200 mg every two weeks along with a 14-week taper of CS (n=60; 1 patient randomized but not treated) or placebo every two weeks along with a 52-week CS taper (n=58). At 52 weeks, the trial met its primary endpoint with 28% of Kevzara-treated patients achieving sustained remission compared to 10% for placebo. Sustained remission was defined as being in disease remission by week 12, absence of disease flare, C-reactive protein normalization from weeks 12 to 52, and adherence to the CS taper protocol from weeks 12 to 52.