MONARCH monotherapy: no new safety signals compared to safety data from KEVZARA combination therapy pivotal trials1,2

Overall, KEVZARA monotherapy long-term safety was studied in 471 patients, with more than 1700 patient-years of exposure, and data were consistent with MONARCH studies2

Mean exposure in the long-term safety population was 3.7 years (max 6.2 years).2

  • 222 patients (47.1%) were treated for >240 weeks (4.6 years)

Incidence rate of AEs was generally stable over time, with no indication of increased incidence rate.1,3

Long-term monotherapy safety

Including MONARCH (MTX-IR) and MONARCH long-term safety populations4*†

Randomized, Controlled Population

Long-Term Safety Population

Adverse Event

Adalimumab
40 mg Q2W
n=184

% (nE/100 PY)

KEVZARA
200 mg Q2W
n=184

% (nE/100 PY)

KEVZARA
Any Dose
n=471

% (nE/100 PY)

Cumulative total TEAE observation period, years§

80.5

80.1

1768.9

Any TEAE

63.6% (326.9)

64.1% (462.0)

89.4% (171.0)

Serious TEAE

6.5% (14.9)

4.9% (18.7)

19.5% (8.6)

TEAE leading to discontinuation

7.1% (19.9)

6.0% (21.2)

16.8% (5.3)

TEAE leading to death||

0% (0)

0.5% (3.7)

2.3% (0.9)

Infections

27.7% (82.0)

28.8% (86.2)

58.0% (44.2)

Serious infections

1.1% (2.5)

1.1% (2.5)

4.5% (1.5)

Bronchitis

3.8% (8.7)

6.5% (18.7)

13.0% (5.6)

Nasopharyngitis

7.6% (18.6)

6.0% (13.7)

17.0% (8.4)

Upper respiratory tract infection

3.8% (11.2)

1.6% (3.7)

12.1% (4.8)

Neutropenia

0.5% (1.2)

13.6% (54.9)

21.2% (16.5)

Headache

6.5% (17.4)

3.8% (11.2)

6.6% (2.9)

Rheumatoid arthritis

3.8% (8.7)

0.5% (1.2)

9.6% (4.2)

Injection site erythema

3.3% (8.7)

7.6% (87.4)

8.3% (17.0)

ALT increase

3.8% (11.2)

3.8% (8.7)

7.4% (2.4)

Accidental overdose#

6.0% (14.9)

3.3% (7.5)

14.4% (5.0)

Dyslipidemia**

4.3% (9.9)

1.6% (3.7)

5.5%(1.5)

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 adalimumab.4

Safety observations in the long-term population were generally consistent with those in the randomized, controlled population.4
nE/100 PY is the exposure-adjusted event rate.5
*Adverse events reported for the safety population were selected based on occurrence in ≥3% of patients in the randomized, controlled population in any treatment group.

111 patients from the KEVZARA ONE study population were included in these long-term monotherapy safety data.5
One patient was randomized, but not treated, in the adalimumab group and was not included in the safety population.6
§TEAE period from day of first treatment dose to 60 days after the last treatment dose.4
||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 36.6
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.6
#Protocol defined as ≥2 doses within 11 calendar days or within 6 days for adalimumab-treated patients who switched to weekly dosing.6
**Dyslipidemia was defined by standardized MedDRA query.6

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 including KEVZARA. Among opportunistic infections, TB, candidiasis, and pneumocystis were reported with KEVZARA. The most frequently observed serious infections with KEVZARA in RA patients included pneumonia and cellulitis.
    • 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 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. Prior to initiating treatment, it is recommended that all patients be brought up to date with all immunizations in agreement with current immunization guidelines.

ADVERSE REACTIONS

  • For Rheumatoid Arthritis: 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.
  • For Polymyalgia Rheumatica: Serious adverse reactions of neutropenia occurred in 2 patients (3.4%) in the KEVZARA group compared to none in the placebo group. The proportion of patients with serious infections was similar in the KEVZARA group (5.1%) compared to the placebo group (5.2%). The common adverse reactions occurring in ≥5% of patients treated with KEVZARA were neutropenia, leukopenia, constipation, rash pruritic, myalgia, fatigue, and injection site pruritus.
  • For Polyarticular Juvenile Idiopathic Arthritis: In Study 4, the rate of infections was 146.6 events per 100 patient-years. The most common infections observed were nasopharyngitis (36.6%) and upper respiratory tract infections (URTI) (14.0%). The most common adverse drug reactions were nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema.

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.
  • Use caution when treating the elderly.

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

Please see full Prescribing Information, including Boxed WARNING.

INDICATIONS

KEVZARA® (sarilumab) 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).
  • adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.
  • patients who weigh 63 kg or greater with active polyarticular juvenile idiopathic arthritis (pJIA).

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 including KEVZARA. Among opportunistic infections, TB, candidiasis, and pneumocystis were reported with KEVZARA. The most frequently observed serious infections with KEVZARA in RA patients included pneumonia and cellulitis.
    • 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 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. Prior to initiating treatment, it is recommended that all patients be brought up to date with all immunizations in agreement with current immunization guidelines.

ADVERSE REACTIONS

  • For Rheumatoid Arthritis: 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.
  • For Polymyalgia Rheumatica: Serious adverse reactions of neutropenia occurred in 2 patients (3.4%) in the KEVZARA group compared to none in the placebo group. The proportion of patients with serious infections was similar in the KEVZARA group (5.1%) compared to the placebo group (5.2%). The common adverse reactions occurring in ≥5% of patients treated with KEVZARA were neutropenia, leukopenia, constipation, rash pruritic, myalgia, fatigue, and injection site pruritus.
  • For Polyarticular Juvenile Idiopathic Arthritis: In Study 4, the rate of infections was 146.6 events per 100 patient-years. The most common infections observed were nasopharyngitis (36.6%) and upper respiratory tract infections (URTI) (14.0%). The most common adverse drug reactions were nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema.

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.
  • Use caution when treating the elderly.

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

Please see full Prescribing Information, including Boxed WARNING.

INDICATIONS

KEVZARA® (sarilumab) 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).
  • adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.
  • patients who weigh 63 kg or greater with active polyarticular juvenile idiopathic arthritis (pJIA).

References: 1. Kevzara [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc. 2. Data on file. Bridgewater, NJ: Sanofi/Regeneron. Integrated Summary of Safety: Appendix 1.3. June 2021. 3. Data on file. Bridgewater, NJ: Sanofi/Regeneron. EXTEND Clinical Study Report. January 2016. 4. Data on file. Bridgewater, NJ: Sanofi/Regeneron. Summary of treatment emergent adverse events-sarilumab MONARCH and monotherapy population (pool 3). April 2023. 5. Burmester GR, Strand V, Kivitz AJ, et al. Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis. Rheumatology (Oxford). 2023;62(10):3268-3279. 6. Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847.

MAT-US-2303591-v2.0-09/2024
Last Updated: September 2024