The FDA has approved kevzara (sarilumab, Regeneron Pharmaceuticals and Sanofi) to treat adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to 1 or more disease-modifying antirheumatic drugs (DMARDs).1 RA, a chronic inflammatory autoimmune disease, affects 1.3 million people in the United States, about 75% of whom are women.2 Kevzara comes as a subcutaneous injection that patients can self-administer.1
PHARMACOLOGY AND PHARMACOKINETICS
Kevzara is a human monoclonal antibody. It is an interleukin-6 (IL-6) receptor antagonist, resulting in the inhibition of IL-6 receptor—mediated signaling. IL-6 is a pro-inflammatory cytokine that can contribute to the inflammation of RA over time.1,2
DOSING AND ADMINISTRATION
Methotrexate or other conventional DMARDs. It should be given as 200 mg subcutaneously every 2 weeks. Patients with an absolute neutrophil count less than 2000/mm3, platelets less than 150,000/mm3, or liver transaminases over 1.5 times the upper limit of normal should not begin treatment with Kevzara. If neutropenia, thrombocytopenia, and/or elevated liver enzymes occur, the dose should be reduced to 150 mg subcutaneously every 2 weeks or discontinued, depending on the laboratory values.1
Kevzara was evaluated in 2 randomized, double-blind, placebo-controlled multicenter studies in patients aged 18 years and older with moderately to severely active RA. In both studies, the primary end point was the improvement in signs and symptoms of RA, as measured by the proportion of patients who achieved a 20% improvement using the American College of Rheumatology criteria at week 24.
Study 1 consisted of 1197 patients who had an inadequate clinical response to methotrexate. Patients received subcutaneous Kevzara 200 mg, Kevzara 150 mg, or placebo every 2 weeks, along with methotrexate. The study found that the Kevzara groups had an improvement in the primary end point, less radiographic progression of disease, and a greater improvement in physical function, compared with the placebo group.
Study 2 consisted of 546 patients who had an inade- quate clinical response or were intolerant to 1 or more TNF-alpha antagonists. Patients received subcutaneous Kevzara 200 mg, Kevzara 150 mg, or placebo every 2 weeks with concurrent conventional DMARDs (meth- otrexate, sulfasalazine, leflunomide, and/or hydroxy- chloroquine). The study found the Kevzara groups to have an improvement in the primary end point and in physical function, compared with the placebo group.1,2
CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS
Kevzara carries a boxed warning stating that patients using it are at increased risk of developing serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens. Patients with an active infection should not use Kevzara, and if a serious infection develops, treatment with Kevzara should be stopped until the infection has resolved. Patients should be tested for latent tuberculosis prior to treatment with Kevzara and monitored for infections throughout treatment with the medication.
Treatment with Kevzara is contraindicated in patients with a known hypersensitivity to the medication or any of its components.
Patients should have laboratory monitoring for the development of neutropenia, thrombocytopenia, ele- vated liver enzymes, or lipid abnormalities during treat- ment of Kevzara. Patients with concurrent diverticulitis, nonsteroidal anti-inflammatory drug use, or corticosteroid use may be at increased risk of gastrointestinal perforation while using Kevzara. Hypersensitivity reactions, such as injection site rash, rash, and urticaria, may occur and may require discontinuation of treatment. Patients using Kevzara should not receive live vaccine. Patients should not breast-feed while using Kevzara.
The most common adverse effects are neutropenia, increased alanine aminotransfarase, injection site erythema, upper respiratory infections, and urinary tract infections.1
Monica Holmberg, PharmD, BCPS, earned her PharmD from the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Health Care System in Arizona. Her practice also has included pediatrics and inpatient mental health. She lives in Phoenix.