Patients treated with sarilumab are at increased risk for developing a serious infection, including bacterial or viral infections or reactivation of viral infections, that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving sarilumab. Most patients who developed an infection were taking concomitant immunosuppressants such as methotrexate or corticosteroids. During and after treatment with sarilumab, closely monitor all patients for the development of signs and symptoms of infection including the possible development of tuberculosis (TB) in patients who tested negative for latent TB infection before sarilumab use. If a serious infection develops, interrupt sarilumab until the infection is controlled. Infections of various types have been reported during clinical trials. During the rheumatoid arthritis placebo-controlled clinical trials of sarilumab plus conventional DMARD, upper respiratory tract infections were reported in 3% and 4% of patients receiving sarilumab 200 mg and 150 mg, respectively (2% placebo). Urinary tract infections were reported in 3% of both sarilumab treatment groups (2% placebo). Naso-pharyngitis also was reported. The rate of serious infections in the 200 mg and 150 mg group was 3.8 to 4.3 and 3 to 4.4 events per 100 patient-years, respectively, compared to 2.5 to 3.1 events per 100 patient-years for placebo. Serious infections reported included pneumonia, cellulitis, and opportunistic infections. Viral reactivation has been reported with the use of immunosuppressive biologic therapies. Herpes zoster was reported in 0.8% and 0.6% of those receiving sarilumab 200 mg and 150 mg, respectively (0.5% placebo). Oral herpes simplex infection occurred in less than 2% of rheumatoid arthritis patients who received sarilumab in clinical trials. In the polymyalgia rheumatica placebo-controlled clinical trial, 3 patients who received sarilumab 200 mg discontinued treatment due to an infection (COVID-19, intervertebral discitis, and pneumonia). However, the overall infection rate was lower in sarilumab group (37.3%) than in the placebo group (50%), and the rate of serious infections was similar (5.1% vs. 5.2%). Herpes zoster was noted in 2 patients who received sarilumab (3.2%) and 1 patient in the placebo group (1.7%). No cases of hepatitis B reactivation were observed in the trials; however, patients who screened positive for hepatitis were excluded from clinical trials. Among opportunistic infections, TB (pulmonary or extrapulmonary disease), candidiasis, and Pneumocystosis infections were reported with sarilumab. Patients have presented with disseminated rather than localized disease and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. Carefully consider the risks and benefits of sarilumab in patients with chronic or recurrent infection.[61976]

Gastrointestinal perforation has been reported during sarilumab clinical trials. Reports of GI perforation were primarily noted as complications of diverticulitis including lower GI perforation and abscesses. One patient experienced a GI perforation during sarilumab clinical trials for rheumatoid arthritis (0.11 events per 100 patient-years). In the long-term safety population, the overall rate of GI perforation was consistent with rates of the controlled periods of the studies. Most patients that developed GI perforations were taking concomitant nonsteroidal anti-inflammatory medications (NSAIDs) or corticosteroids. The contribution of these concomitant medications to the development of GI perforations is not known. In the polymyalgia rheumatica clinical trial, 6.8% of drug recipients experienced constipation.[61976]

Sarilumab may cause neutropenia; neutrophil counts should be assessed before and during treatment. During the rheumatoid arthritis placebo-controlled clinical trials of sarilumab plus conventional DMARD, neutropenia was reported in 10% of those who received sarilumab 200 mg and 7% of those who received sarilumab 150 mg. Decreases in neutrophil counts to less than 1,000/mm³ occurred in 6% and 4% of the patients in the sarilumab 200 mg and 150 mg groups, respectively (0% placebo). Severe decreases in neutrophil counts to less than 500/mm³ were reported in 0.7% of both sarilumab treatment groups. Neutropenia was not associated with the occurrence of infections, including serious infections. In the polymyalgia rheumatica clinical trial, 15.3% of adults treated with sarilumab 200 mg developed neutropenia, and 3 patients (5.1%) required permanent treatment discontinuation because of neutropenia. Two patients (3.4%) developed neutrophil counts less than 500/mm³ without any infections. In both cases, the neutrophil counts resolved once sarilumab therapy was stopped. Leukopenia has also been reported. In the rheumatoid arthritis trial, leukopenia was reported in 0.9% of patients receiving sarilumab 150 mg and 2% of patients receiving the 200 mg dose. Leukopenia was also reported in the polymyalgia rheumatica clinical trial, occurring in 6.8% of drug recipients.[61976]

Sarilumab may cause thrombocytopenia; platelet counts should be assessed before and during treatment. During the rheumatoid arthritis placebo-controlled clinical trials of sarilumab plus conventional DMARD, decreases in platelet counts to less than 100,000/mm³ occurred in 1% and 0.7% of those receiving sarilumab 200 mg and 150 mg, respectively (0% placebo). In the polymyalgia rheumatica clinical trial, decreases in platelet counts between 75,000 and 100,000/mm³ occurred in 2 patients (3.4%) who received sarilumab 200 mg, compared to no patient in the placebo group. Treatment-related reductions in platelet counts were not associated with bleeding events in clinical trials.[61976]

Sarilumab is associated with elevated hepatic enzymes. Liver function tests should be assessed before and during sarilumab treatment. In those experiencing elevated liver enzymes, modification of the treatment regimen (i.e., dose reduction or interruption) usually results in a decrease or normalization of the liver enzyme. During the rheumatoid arthritis placebo-controlled clinical trials of sarilumab plus conventional DMARD, an AST greater than the upper limit of normal (ULN) to 3-times ULN or less were reported in 30% of patients receiving sarilumab 200 mg and 27% of those receiving 150 mg compared to 15% of those receiving placebo. AST elevations of more than 3-times the ULN to 5-times the ULN were reported in 1% (0% for placebo), and AST more than 5-times ULN were reported in 0.2% to 0.7% (0% for placebo) of those receiving any dose of sarilumab. Similarly, ALT more than the ULN up to 3-times ULN were reported in 43% of patients receiving sarilumab 200 mg and 38% of those receiving 150 mg vs. 25% of those receiving placebo. ALT elevations of more than 3-times the ULN to 5-times the ULN were reported in 3% to 4% of those receiving any dose of sarilumab (1% for placebo), and ALT greater than 5-times ULN were reported in 0.7% to 1% of those receiving sarilumab (0% for placebo). These increases in liver enzymes were not associated with clinically relevant increases in direct bilirubin or evidence of hepatitis or hepatic impairment. In the polymyalgia rheumatica clinical trial, no patient who received treatment with sarilumab 200 mg/dose experienced an ALT or AST greater than 3-times the ULN.[61976]

An injection site reaction may occur with the use of sarilumab. In the rheumatoid arthritis clinical trials, injection site reactions were reported in 7% and 6% of those who received sarilumab 200 mg and sarilumab 150 mg, respectively. Injection site reactions included pruritus (2%) and erythema (4% to 5%). Mild injection site pruritis was also noted in 3 patients (5.1%) who received sarilumab 200 mg during the polymyalgia rheumatica clinical trial.[61976]

Hypersensitivity reactions have been reported with the administration of sarilumab. In the rheumatoid arthritis clinical trials, reactions that required treatment discontinuation were reported in 0.2 to 0.3% of patients. Injection site rash, rash (unspecified), and urticaria were reported most frequently. In the polymyalgia rheumatica clinical trial, pruritic rash (5.1%) was among the most common adverse reactions. Advise patients to seek medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylactoid reactions or other hypersensitivity reaction occurs, immediately stop the administration of sarilumab.[61976]

Sarilumab may cause hyperlipidemia, including hypercholesterolemia and hypertriglyceridemia. Lipid parameters should be assessed during sarilumab treatment. During the rheumatoid arthritis placebo-controlled trials of sarilumab plus conventional DMARD, lipid parameters were measured 4 weeks following sarilumab initiation. Among those receiving sarilumab 150 mg, the mean LDL cholesterol increased by 12 mg/dL, mean triglycerides increased by 20 mg/dL, and mean HDL increased by 3 mg/dL. Among those receiving sarilumab 200 mg, the mean LDL increased by 16 mg/dL, mean triglycerides increased by 27 mg/dL, and mean HDL increased by 3 mg/dL. In the long-term safety population, the observations in lipid parameters were consistent with what was observed in the rheumatoid arthritis trials. In the polymyalgia rheumatica clinical trial, cholesterol levels of 299.27 mg/dL or greater were observed in 8 patients (13.8%) who received sarilumab 200 mg compared to 4 patients (6.9%) in the placebo group. Triglyceride levels of at least 407.4 mg/dL were observed in 3 sarilumab patients (5.2%) and 1 placebo patient (1.7%). At treatment Week 52, mean increases from baseline for LDL and triglycerides were observed in the sarilumab group, though both remained within the normal range. There was no difference in mean HDL levels between the sarilumab and placebo.[61976]

In the polymyalgia rheumatica clinical trial, myalgia (6.8%) and fatigue (5.1%) were among the most common adverse reactions in PMR patients who received treatment with sarilumab 200 mg.[61976]

In rheumatoid arthritis patients treated with sarilumab monotherapy, 9.2% of patients exhibited an anti-drug antibody (ADA) response with 6.9% of patients also exhibiting neutralizing antibodies (NAbs). Prior to the administration of sarilumab, 2.3% of patients exhibited an ADA response. In the pre-rescue population, 4% of patients treated with sarilumab 200 mg plus DMARD and 5.7% of patients treated with sarilumab 150 mg plus DMARD exhibited an ADA response, compared with 1.9% of patients receiving placebo plus DMARD. Neutralizing antibodies were detected in 1% of patients on sarilumab 200 mg plus DMARD and 1.6% of patients on sarilumab 150 mg plus DMARD (versus 0.2% of patients on placebo plus DMARD). No correlation was observed between antibody formation and adverse events or loss of efficacy. In the polymyalgia rheumatica population, 1 patient (1.8%) who received sarilumab 200 mg plus 14-week corticosteroid taper exhibited an ADA response, compared with no patient in the placebo plus 52-week corticosteroid taper group. Neutralizing antibodies were detected in the sarilumab recipient, and that patient did not demonstrate a clinical response. Due to the low occurrence of ADA, the effect of these antibodies on safety and effectiveness of sarilumab is unknown.[61976]

Sarilumab may increase the risk for a new primary malignancy. In the 52-week placebo-controlled trial, 9 malignancies (exposure-adjusted event rate of 1 event per 100 patient-years) were reported in patients receiving sarilumab and a DMARD compared to 4 malignancies (exposure-adjusted event rate of 1 event per 100 patient-years) in the control group. In the long-term safety population, the rate of malignancies was consistent with the rate observed in the placebo-controlled period.[61976]

Patients who receive sarilumab are at increased risk for developing serious infections that may lead to hospitalization or death. Infections include active tuberculosis (TB) and invasive fungal infections including candidiasis and pneumocystis. Bacterial, viral, and other infections due to opportunistic pathogens have been reported. Most patients who developed serious infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Patients with an invasive fungal infection may present with disseminated disease, and TB may present as pulmonary or extrapulmonary disease. Evaluate patients for TB risk factors before starting sarilumab. Also, test patients for latent TB before and during sarilumab receipt. Initiate treatment for latent infection before sarilumab use. Consider anti-TB therapy prior to sarilumab initiation for 2 patient groups: patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed and patients with a negative test for latent TB but with risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision whether initiating anti-TB therapy is appropriate for an individual patient. Carefully consider the risks and benefits of sarilumab before initiating therapy in patients with chronic or recurrent infection, who have been exposed to TB, with a history of a serious or opportunistic infection, with underlying conditions that may predispose them to infection (e.g., patients with advanced or uncontrolled diabetes mellitus, human immunodeficiency virus (HIV) infection, or immunosuppression), or who have resided or traveled in areas of endemic tuberculosis or endemic mycoses. Do not start treatment with sarilumab in patients with an absolute neutrophil count (ANC) less than 2,000/mm³. For rheumatoid arthritis (RA) patients who experience reduced neutrophil counts while taking sarilumab, discontinuation is advised if the ANC drops below 500/mm³ and treatment interruption is advised for an ANC between 500 and 1,000/mm³. For polymyalgia rheumatica patients, sarilumab discontinuation is recommended if the ANC drops below 1,000/mm³ at the end of the dosing interval. Closely monitor patients for the development of signs and symptoms of infection; signs and symptoms of acute inflammation may be lessened due to suppression of the acute phase reactants. Consider the possible development of TB in patients who tested negative for latent TB infection prior to taking sarilumab. Viral reactivation has been observed during immunosuppressive biologic therapies. Do not administer sarilumab to a patient with an active infection including localized infections. If a serious infection such as sepsis or influenza or an opportunistic infection develops, interrupt sarilumab receipt until the infection is controlled. If a new infection develops during sarilumab receipt, complete a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy, and closely monitor the patient.[61976]

Initiation of sarilumab therapy is not recommended in patients with thrombocytopenia defined as a platelet count less than 150,000/mm³ or for neutropenia defined as an absolute neutrophil count (ANC) below 2,000/mm³. Thrombocytopenia and neutropenia have occurred with sarilumab, and drug interruption, dose reduction, or discontinuation may be needed. Assess platelet count and ANC before sarilumab receipt, 4 to 8 weeks after sarilumab initiation, and every 3 months thereafter.[61976]

Sarilumab is not recommended in patients with active hepatic disease or hepatic impairment. Initiation of sarilumab is not recommended in patients who have ALT or AST more than 1.5 times the upper limit of normal (ULN). Hepatic enzyme elevations observed in clinical trials with sarilumab did not result in any clinically evident hepatic injury. Elevated transaminases have been noted with sarilumab, and drug interruption, dose reduction, or discontinuation may be needed. Assess liver function tests (LFTs) before sarilumab receipt, 4 to 8 weeks after start of therapy, and every 3 months thereafter. Consider assessing other liver function tests such as bilirubin when clinically indicated. The safety and efficacy of sarilumab have not been studied in patients with hepatic impairment including patients with positive hepatitis B virus (HBV) or hepatitis C virus (HCV) serology. The risk of hepatitis B reactivation with sarilumab is unknown since patients who were at risk for reactivation were excluded from clinical trials.[61976]

Gastrointestinal (GI) perforations have been reported in clinical studies, primarily as complications of diverticulitis. Use with caution in patients with diverticulitis. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or in those receiving corticosteroid therapy. Promptly evaluate patients presenting with new onset abdominal symptoms.[61976]

Sarilumab is an immunosuppressant; therefore, sarilumab may affect host defenses against neoplastic disease. The impact of sarilumab on the development of malignancies is unknown, but malignancies were observed in clinical studies. Consider the risks and benefits of sarilumab before treatment initiation in patients with a known malignancy. Also, consider the risks and benefits of sarilumab continuation in patients who develop a malignancy.[61976]

Cautious use of sarilumab may be warranted for patients with hyperlipidemia, hypercholesterolemia, or hypertriglyceridemia. Increased total cholesterol, increased HDL-C, increased LDL-C, and increased triglycerides may occur with sarilumab. Assess lipid parameters approximately 4 to 8 weeks after sarilumab initiation and subsequently at approximately 6 month intervals. Manage patients according to clinical guidelines [e.g., National Cholesterol Educational Program (NCEP)] for the management of hyperlipidemia.[61976]

Live virus vaccines should not be given concurrently with sarilumab due to the potential increase in risk of infection. The safety of live virus vaccination in patients receiving sarilumab has not been established. No data exist on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab should be in accordance with current vaccination guidelines regarding immunosuppressive agents.[61976]

Limited available data are not sufficient to determine whether the use of sarilumab during human pregnancy is associated with risk for major birth defects or miscarriage. Monoclonal antibodies, like sarilumab, are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. This may affect immune response in the in utero exposed infant. Concentrations of immunoglobulin G (IgG), in response to antigen challenge, may be reduced in the fetus/infant of treated mothers. Consider risks and benefits prior to administering live or live-attenuated vaccines to neonates or infants who were exposed to sarilumab in utero. In an animal reproduction study, consisting of a combined embryo-fetal and pre- and postnatal development study with monkeys that received intravenous administration of sarilumab, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 84 times the maximum recommended human dose (MRHD). Animal data suggest sarilumab may affect labor and obstetric delivery. Inhibition of IL-6 signaling may interfere with cervical ripening and dilatation and myometrial contractile activity, leading to potential delays in parturition. For mice deficient in IL-6, parturition was delayed relative to wild-type mice without this deficiency. Administration of recombinant IL-6 to the deficient mice restored the normal timing of delivery.[61976]

There is no information available on the presence of sarilumab in human milk or its effects on the breast-fed infant or milk production. Maternal immunoglobulin G (IgG) is present in human milk. The effects of local exposure on the gastrointestinal tract and potential limited systemic exposure to the infant are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for sarilumab and the potential adverse effects on the breast-fed infant from sarilumab or the underlying maternal condition.[61976]

During the rheumatoid arthritis clinical trials, the rate of serious infections among geriatric adults was higher compared to that of adults less than 65 years of age. There were no overall differences in safety observed between older and younger adults in the polymyalgia rheumatica trial. Because there is a higher incidence of infections in the older adult in general, cautious use of sarilumab is advised.[61976]

The safety and efficacy of sarilumab have not been established in pediatric patients (adolescents, children or infants).[61976]