safety-img
SAFETY DATA
KEVZARA has an established safety profile
and safety data up to 7 years with no
unexpected safety signals
COMBINATION THERAPY

COMMON ADVERSE REACTIONS IN PRE-RESCUE, PLACEBO-CONTROLLED TRIALS1*

PreferredTermNeutropenia10%7%0.2%ALTincreased5%5%2%Injection siteerythema4%5%0.9%Injection sitepruritus2%2%0.2%Upper respiratorytract infection3%4%2%Urinary tractinfection3%3%2%Hypertriglyceridemia1%3%0.5%Leukopenia2%0.9%0%Placebo+ DMARD(s)N=579KEVZARA 150 mg+DMARD(s)N=579KEVZARA 200 mg+DMARD(s)N=582

*Adverse reactions occurring in ≥2% of patients administered KEVZARA 200 mg or KEVZARA 150 mg + DMARD(s) and greater than observed in patients on placebo + DMARD(s).

  • Medically relevant AE occurring at an incidence of less than 2% in patients with RA treated with KEVZARA in controlled studies was oral herpes1
  • Decrease in ANC was not associated with higher incidence of infections, including serious infections1
  • In the long-term safety population, the overall rates of serious infections, GI perforations, neutrophil counts, platelet counts, and lipid parameters were consistent with what was observed in the placebo-controlled trials1

DMARDs=disease-modifying antirheumatic drugs; ALT=alanine aminotransferase; ANC=absolute neutrophil count; GI=gastrointestinal.

LONG-TERM COMBINATION THERAPY

Studied in ≈3000 MTX-IR and TNF-IR patients with over 8100 patient-years of exposure1-3

Mean duration of treatment in the safety population (N=2887) was 2.8 years (max 7.3 years), representing 8188 cumulative PY of exposure

  • 773 patients (27%) were treated for ≥240 weeks (4.6 years)
  • 36 patients (1.2%) were treated for >360 weeks (7 years)

Incidence rate of AEs was generally stable over time, with no indication of increased incidence rate in serious AEs and serious infections.2,3

MOBILITY (MTX-IR), TARGET (TNF-IR), LONG-TERM SAFETY POPULATIONS2,3

Placebo-Controlled PopulationLong-TermSafetyPopulationKEVZARA 200 mgor 150 mg q2wMTX/DMARD(s)N=2887KEVZARA 200 mgq2w MTX/DMARD(s)n=661KEVZARA 150 mgq2w MTX/DMARD(s)n=660Placebo +MTX/DMARD(s)n=661Adverse Event (IR/100 PY)*8187.7Cumulative total TEAEobservation period, years440.7382.3441.4144.2Any TEAE215.7173.3252.09.4Serious TEAE9.78.313.88.7TEAE leading to discontinuation16.88.219.40.4TEAE leading to death0.50.80.254.4Overall infections80.875.184.53.7Serious infections3.63.95.27.7Upper respiratory tract infection12.310.212.55.97.07.810.913.822.90.831.0Urinary tract infectionNeutropenia5.011.64.410.913.329.31.623.8ALT increasedInjection site erythema6.99.30.59.32.84.51.33.2Injection site pruritusHypertriglyceridemia3.74.107.9Leukopenia
upto-40-percent

In the long-term safety population, the rate of thromboembolic events (MedDRA high-level group term “embolism and thrombosis”) was 0.8 per 100 PY (as reported and evaluated post hoc; not a prespecified AESI)2

  • Rate of DVT was 0.2 per 100 PY; rate of PE was 0.2 per 100 PY

Safety observations in the open-label extension population were consistent with those in the placebo-controlled trials.2,3

*Incidence rate per 100 PY at risk of first event.

TEAE period from day of first treatment dose to 60 days after the last treatment dose.2

Injection site reactions (including erythema and pruritus) were mild in severity for the majority of patients and necessitated drug discontinuation in 3 (<0.5%) patients receiving KEVZARA.3

MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; PY=patient-years; IR=incidence rate; MTX=methotrexate; DMARDs=disease-modifying antirheumatic drugs; q2w=every 2 weeks; TEAE=treatment-emergent adverse event; ALT=alanine aminotransferase; AESI=adverse event of special interest; DVT=deep vein thrombosis; PE=pulmonary embolism.

MONOTHERAPY

MONARCH: NO UNEXPECTED SAFETY SIGNALS WITH KEVZARA

Overall, KEVZARA monotherapy long-term safety was studied in 471 patients, with ≈800 patient-years of exposure, and data were consistent with MONARCH studies1

Mean exposure in the long-term safety population was 1.7 years (max 3.5 years)

  • 320 patients (87%) were treated for ≥72 weeks

Incidence rate of AEs was generally stable over time, with no indication of increased incidence rate2,3

MONARCH (MTX-IR) AND MONARCH LONG-TERM SAFETY POPULATIONS2,3*

Randomized, Controlled PopulationLong-Term Safety PopulationAny TEAESerious TEAETEAE leading to discontinuationTEAE leading to deathInfectionsSerious infections§BronchitisNeutropeniaHeadacheRheumatoid arthritisInjection site erythemaALT increaseNasopharyngitisUpper respiratory tract infectionAccidental overdoseIIKEVZARA 200 mgq2w n=320% (nE/100 PY)§KEVZARA 200 mgq2w n=184% (nE/100 PY)§Adalimumab 40 mgq2w n=184% (nE/100 PY)§73.4% (247.9)63.6% (326.9)64.1% (462.0)7.2% (9.5)6.5% (14.9)4.9% (18.7)6.9% (7.8)7.1% (19.9)6.0% (21.2)0.9% (1.1)0% (0)0.5% (3.7)38.8% (59.5)27.7% (82.0)28.8% (86.2)0.9% (0.9)1.1% (2.5)1.1% (2.5)7.5% (7.2)3.8% (8.7)6.5% (18.7)11.9% (13.5)7.6% (18.6)6.0% (13.7)6.6% (6.9)3.8% (11.2)1.6% (3.7)13.1% (28.2)0.5% (1.2)13.6% (54.9)2.8% (5.5)6.5% (17.4)3.8% (11.2)3.8% (4.3)3.8% (8.7)0.5% (1.2)7.8% (35.1)3.3% (8.7)7.6% (87.4)4.4% (5.8)3.8% (12.4)3.8% (8.7)5.3% (6.6)6.0% (14.9)3.3% (7.5)3.1% (3.2)4.3% (9.9)1.6% (3.7)Dyslipidemia
afety-table

In MONARCH, the safety profiles of KEVZARA and adalimumab were generally comparable, except for neutropenia and injection site erythema for KEVZARA and headache and RA for adalimumab3

Safety observations in the long-term population were generally consistent with those in the randomized, controlled population.4

*Adverse events reported for the long-term safety population were selected based on occurrence in ≥3% of patients in the randomized, controlled population in any treatment group; Patients from the KEVZARA ONE study population were included in these long-term monotherapy safety data; One patient was randomized, but not treated, in the adalimumab group and was not included in the safety population; §Patient years per group are as follows: 80.5 (adalimumab 40 mg), 80.1 (KEVZARA 200 mg), and 348.1 (long-term safety population for KEVZARA 200 mg). ||In the randomized trial, 1 patient in the KEVZARA group died of acute cardiac failure secondary to aortic dissection and papillary muscle rupture on day 36; In the randomized trial, 1 patient receiving KEVZARA was diagnosed with infective bursitis and another patient was diagnosed with mastitis, and 1 patient receiving adalimumab was diagnosed with bacterial arthritis and another patient was diagnosed with a respiratory tract infection; #Protocol defined as ≥2 doses within 11 calendar days or within 6 days for adalimumab-treated patients who switched to weekly dosing; Dyslipidemia was defined by standardized MedDRA query.2,3

MTX-IR=methotrexate inadequate response; q2w=once every 2 weeks; PY=patient-years; IR=incidence rate; TEAE=treatment emergent adverse event; ALT=alanine aminotransferase.

INDICATION

KEVZARA is indicated for 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).

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS INFECTIONS
Patients treated with KEVZARA are at increased risk for developing serious infections that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving KEVZARA. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Avoid use of KEVZARA in patients with an active infection.
Reported infections include:
  • Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before KEVZARA use and during therapy. Treatment for latent infection should be initiated prior to KEVZARA use.
  • Invasive fungal infections, such as candidiasis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.
Closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. If a serious infection develops, interrupt KEVZARA until the infection is controlled.
Consider the risks and benefits of treatment with KEVZARA prior to initiating therapy in patients with chronic or recurrent infection.

CONTRAINDICATION

Do not use KEVZARA in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.

WARNINGS AND PRECAUTIONS

  • Infections. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents for rheumatoid arthritis (RA). The most frequently observed serious infections with KEVZARA included pneumonia and cellulitis. Among opportunistic infections, TB, candidiasis, and pneumocystis were reported with KEVZARA.
    • Hold treatment with KEVZARA if a patient develops a serious infection or an opportunistic infection.
    • Patients with latent TB should be treated with standard antimycobacterial therapy before initiating KEVZARA. Consider anti-TB therapy prior to initiation of KEVZARA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection.
    • Consider the risks and benefits of treatment prior to initiating KEVZARA in patients who have: chronic or recurrent infection, a history of serious or opportunistic infections, underlying conditions in addition to RA that may predispose them to infection, been exposed to TB, or lived in or traveled to areas of endemic TB or endemic mycoses.
    • Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with KEVZARA.
  • Laboratory Abnormalities. Treatment with KEVZARA was associated with decreases in absolute neutrophil counts (including neutropenia), and platelet counts; and increases in transaminase levels and lipid parameters (LDL, HDL cholesterol, and/or triglycerides). Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with KEVZARA. Assess neutrophil count, platelet count, and ALT/AST levels prior to initiation with KEVZARA. Monitor these parameters 4 to 8 weeks after start of therapy and every 3 months thereafter. Assess lipid parameters 4 to 8 weeks after start of therapy, then at 6 month intervals.
  • Gastrointestinal Perforation. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Gastrointestinal perforations have been reported in clinical studies, primarily as complications of diverticulitis. Promptly evaluate patients presenting with new onset abdominal symptoms.
  • Immunosuppression. Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with KEVZARA on the development of malignancies is not known but malignancies have been reported in clinical studies.
  • Hypersensitivity Reactions. Hypersensitivity reactions have been reported in association with KEVZARA. Hypersensitivity reactions that required treatment discontinuation were reported in 0.3% of patients in controlled RA trials. Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of KEVZARA immediately. Do not administer KEVZARA to patients with known hypersensitivity to sarilumab.
  • Active Hepatic Disease and Hepatic Impairment. Treatment with KEVZARA is not recommended in patients with active hepatic disease or hepatic impairment, as treatment with KEVZARA was associated with transaminase elevations.
  • Live Vaccines. Avoid concurrent use of live vaccines during treatment with KEVZARA due to potentially increased risk of infections. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving KEVZARA.

ADVERSE REACTIONS

  • The most common serious adverse reactions were infections. The most frequently observed serious infections included pneumonia and cellulitis. The most common adverse reactions (occurred in at least 3% of patients treated with KEVZARA + DMARDs) are neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.

DRUG INTERACTIONS

  • Exercise caution when KEVZARA is co-administered with CYP substrates with a narrow therapeutic index (e.g. warfarin or theophylline), or with CYP3A4 substrates (e.g. oral contraceptives or statins) as there may be a reduction in exposure which may reduce the activity of the CYP3A4 substrate.
  • Elevated interleukin-6 (IL-6) concentration may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA. Blockade of IL-6 signaling by IL-6Rα antagonists such as KEVZARA might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered drug concentrations.

USE IN SPECIFIC POPULATIONS

  • KEVZARA should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Because monoclonal antibodies could be excreted in small amounts in human milk, the benefits of breastfeeding and the potential adverse effects on the breastfed child should be considered along with the mother’s clinical need for KEVZARA.
  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to KEVZARA during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-89721-877-311-8972.
  • Use caution when treating the elderly.

Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

KEVZARA is available by prescription only.

Click here for full Prescribing Information, including Boxed WARNING.

INDICATION

KEVZARA is indicated for 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).

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS INFECTIONS
Patients treated with KEVZARA are at increased risk for developing serious infections that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving KEVZARA. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Avoid use of KEVZARA in patients with an active infection.
Reported infections include:
  • Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before KEVZARA use and during therapy. Treatment for latent infection should be initiated prior to KEVZARA use.
  • Invasive fungal infections, such as candidiasis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.
Closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. If a serious infection develops, interrupt KEVZARA until the infection is controlled.
Consider the risks and benefits of treatment with KEVZARA prior to initiating therapy in patients with chronic or recurrent infection.

CONTRAINDICATION

Do not use KEVZARA in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.

WARNINGS AND PRECAUTIONS

  • Infections. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents for rheumatoid arthritis (RA). The most frequently observed serious infections with KEVZARA included pneumonia and cellulitis. Among opportunistic infections, TB, candidiasis, and pneumocystis were reported with KEVZARA.
    • Hold treatment with KEVZARA if a patient develops a serious infection or an opportunistic infection.
    • Patients with latent TB should be treated with standard antimycobacterial therapy before initiating KEVZARA. Consider anti-TB therapy prior to initiation of KEVZARA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection.
    • Consider the risks and benefits of treatment prior to initiating KEVZARA in patients who have: chronic or recurrent infection, a history of serious or opportunistic infections, underlying conditions in addition to RA that may predispose them to infection, been exposed to TB, or lived in or traveled to areas of endemic TB or endemic mycoses.
    • Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with KEVZARA.
  • Laboratory Abnormalities. Treatment with KEVZARA was associated with decreases in absolute neutrophil counts (including neutropenia), and platelet counts; and increases in transaminase levels and lipid parameters (LDL, HDL cholesterol, and/or triglycerides). Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with KEVZARA. Assess neutrophil count, platelet count, and ALT/AST levels prior to initiation with KEVZARA. Monitor these parameters 4 to 8 weeks after start of therapy and every 3 months thereafter. Assess lipid parameters 4 to 8 weeks after start of therapy, then at 6 month intervals.
  • Gastrointestinal Perforation. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Gastrointestinal perforations have been reported in clinical studies, primarily as complications of diverticulitis. Promptly evaluate patients presenting with new onset abdominal symptoms.
  • Immunosuppression. Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with KEVZARA on the development of malignancies is not known but malignancies have been reported in clinical studies.
  • Hypersensitivity Reactions. Hypersensitivity reactions have been reported in association with KEVZARA. Hypersensitivity reactions that required treatment discontinuation were reported in 0.3% of patients in controlled RA trials. Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of KEVZARA immediately. Do not administer KEVZARA to patients with known hypersensitivity to sarilumab.
  • Active Hepatic Disease and Hepatic Impairment. Treatment with KEVZARA is not recommended in patients with active hepatic disease or hepatic impairment, as treatment with KEVZARA was associated with transaminase elevations.
  • Live Vaccines. Avoid concurrent use of live vaccines during treatment with KEVZARA due to potentially increased risk of infections. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving KEVZARA.

ADVERSE REACTIONS

  • The most common serious adverse reactions were infections. The most frequently observed serious infections included pneumonia and cellulitis. The most common adverse reactions (occurred in at least 3% of patients treated with KEVZARA + DMARDs) are neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.

DRUG INTERACTIONS

  • Exercise caution when KEVZARA is co-administered with CYP substrates with a narrow therapeutic index (e.g. warfarin or theophylline), or with CYP3A4 substrates (e.g. oral contraceptives or statins) as there may be a reduction in exposure which may reduce the activity of the CYP3A4 substrate.
  • Elevated interleukin-6 (IL-6) concentration may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA. Blockade of IL-6 signaling by IL-6Rα antagonists such as KEVZARA might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered drug concentrations.

USE IN SPECIFIC POPULATIONS

  • KEVZARA should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Because monoclonal antibodies could be excreted in small amounts in human milk, the benefits of breastfeeding and the potential adverse effects on the breastfed child should be considered along with the mother’s clinical need for KEVZARA.
  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to KEVZARA during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-89721-877-311-8972.
  • Use caution when treating the elderly.

Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

KEVZARA is available by prescription only.

Click here for full Prescribing Information, including Boxed WARNING.