KEVZARA has over 4 years of clinical remission data as monotherapy1,2

    MOBILITY study design

    After Week 16 in MOBILITY, patients with an inadequate response could have been treated with open-label KEVZARA 200 mg every 2 weeks.3,4​​​​​​

    CO-PRIMARY ENDPOINT DATA3,4

    ACR20 RESPONSE AT WEEK 24:
    Patients achieved 66%* with KEVZARA 200 mg + MTX compared to 33% with placebo + MTX

    ΔHAQ-DI AT WEEK 16:
    -0.55* with KEVZARA 200 mg + MTX compared to -0.29 with placebo + MTX

    ΔMTSS FROM BASELINE AT WEEK 52:
    0.25 with KEVZARA 200 mg + MTX vs 2.78 with placebo + MTX*: KEVZARA 200 mg + MTX provided an absolute difference of -2.52 units (CI: -3.38, -1.66) in mean ΔmTSS relative to placebo + MTX

    TARGET study design

    CO-PRIMARY ENDPOINT DATA3,5

    ACR20 RESPONSE AT WEEK 24:
    Patients achieved 61%* with KEVZARA 200 mg + DMARD(s) compared to 34% with placebo + DMARD(s)

    ΔHAQ-DI AT WEEK 12:
    -0.49† with KEVZARA 200 mg + DMARD(s) compared to -0.29 with placebo + DMARD(s)

    *P<0.0001.4,5
    †P<0.001.5
    ACR20=American College of Rheumatology 20% improvement criteria; anti-CCP=anti-cyclic citrullinated peptide; CI=confidence interval; DMARDs=disease-modifying antirheumatic drugs;HAQ-DI=Health Assessment Questionnaire-Disability Index; hsCRP=high-sensitivity C-reactive protein; mTSS=modified Total Sharp Score; MTX=methotrexate; Q2W=once every 2 weeks; RA=rheumatoid arthritis; RF=rheumatoid factor; SJC=swollen joint count; TJC=tender joint count; TNFi=tumor necrosis factor inhibitor.

    MONARCH monotherapy study design, context, and limitations1

    MONARCH study design

    MONARCH study design

    • A 24-week, randomized, double-blind, double-dummy, phase 3 superiority study
      • Efficacy analyses were conducted in the ITT population, which included all randomized patients, including those who increased the dose frequency of adalimumab or matching placebo. Data collected after permanent treatment discontinuation period were excluded

    Primary endpoint data4‡

    • Change from baseline DAS28-ESR at 24 weeks: -3.28§ with KEVZARA 200 mg Q2W monotherapy compared to -2.20 with adalimumab 40 mg Q2W monotherapy
    • 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

    ‡After week 16, dose escalation to adalimumab QW was permitted for patients who did not achieve ≥20% improvement in TJC and SJC.6

    §P<0.0001; difference: -1.08 (95% CI: -1.36 to -0.79)

    MONARCH study context and limitations

    Additional study context1,3

    • MONARCH data are not included in the KEVZARA US full Prescribing Information
    • DAS28-ESR and FACIT-Fatigue were endpoints in MONARCH; however, there are no DAS28-ESR or FACIT-Fatigue data in the KEVZARA US full Prescribing Information

    Use of adalimumab

    • Adalimumab and KEVZARA have different indications and can be used differently in clinical practice3,7
    • Dose escalation from adalimumab 40 mg Q2W to 40 mg QW was permitted after Week 16 in patients who had not achieved at least 20% improvement in TJC and SJC. By Week 24, dosing for 8.6% of patients on adalimumab was adjusted6

    Study limitations1,3,7

    • KEVZARA and adalimumab can be used as monotherapy or in combination with nonbiologic DMARDs. In MONARCH, both agents were only used as monotherapy
    • The efficacy of KEVZARA monotherapy has not been compared to that of KEVZARA + MTX or adalimumab + MTX
    • MONARCH did not evaluate radiographic outcomes in either treatment group

    Given the limitations and context described above, caution should be used in interpreting monotherapy data.

    ACR20=American College of Rheumatology 20% improvement criteria; CI=confidence interval; CRP=high-sensitivity C-reactive protein; DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; DMARDs=disease-modifying antirheumatic drugs; ESR=Erythrocyte Sedimentation Rate; FACIT-Fatigue=Functional Assessment of Chronic Illness-Fatigue Scale; HAQ-DI=Health Assessment Questionnaire-Disability Index; MTX=methotrexate; QW=once weekly; Q2W=once every 2 weeks; RA=rheumatoid arthritis; SJC=swollen joint count; TJC=tender joint count.

DAS28-CRP
CDAI at Week 24
DAS28-CRP <2.6 Over 4 Years
CDAI ≤2.8 Over 4 Years
MONARCH OLE Study Design

Data presented are descriptive in nature and no statistical comparisons are made.

Change in DAS28-CRP with KEVZARA at Week 241

line graph showing MONARCH clinical remission data

DAS28-CRP was not a prespecified endpoint.1

Measures of remission do not imply drug-free remission or complete absence of disease.

DAS28-CRP=Disease Activity Score 28-C-reactive protein; SE=standard error.

Clinical remission data (CDAI) with KEVZARA at Week 241

Bar graph showing incidence of CDAI

CDAI was a prespecified secondary endpoint, though not part of the hierarchy.1

Measures of remission do not imply drug-free remission or complete absence of disease.
IINominal P<0.05; P value is for descriptive purposes only and is not adjusted for multiplicity.1
Nominal P<0.01; P value is for descriptive purposes only and is not adjusted for multiplicity.1
CDAI=Clinical Disease Activity Index.

Given the limitations and context described below, caution should be used in interpreting OLE data. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.

MONARCH open-label extension data

Clinical remission data (DAS28-CRP <2.6) over 4 years2,8

line graph showing incidence of DAS28-CRP

Measures of remission do not imply drug-free remission or complete absence of disease.
Given the limitations of OLE data, caution should be used when interpreting these data.

MONARCH open-label extension data

Clinical remission data (CDAI ≤2.8) over 4 years2,8

line graph showing incidence of CDAI over 4 years

Measures of remission do not imply drug-free remission or complete absence of disease.
Given the limitations of OLE data, caution should be used when interpreting these data.

Monotherapy open-label extension study design and limitations9

MONARCH long-term study design

#Patients who rolled over to open-label extension period.9

Open-label extension (OLE) study design: A 276-week randomized, double-blind, double-dummy phase 3 superiority study extension designed to assess the safety and efficacy of long-term continuous KEVZARA monotherapy and switching from adalimumab monotherapy to KEVZARA monotherapy in 320 adult patients who completed the MONARCH study. Primary endpoint was safety. Secondary endpoints included DAS28-ESR, DAS28-CRP, HAQ-DI, CDAI, SDAI, and ACR20/50/70.2,8

Primary endpoint data8

  • Overall, safety observations in the OLE population were consistent with those in the MONARCH study and previous studies of KEVZARA, with no unexpected safety signals
  • Long-term safety and efficacy of KEVZARA were demonstrated in patients who continued treatment with KEVZARA from MONARCH through OLE ≥72 weeks

MONARCH long-term study context and limitations

OLE and additional study context

  • These data are not included in the KEVZARA US full Prescribing Information
  • Long-term safety analysis included all patients who received at least 1 dose of KEVZARA monotherapy
  • Analysis of clinical data was based on all available data as observed
  • Data presented are descriptive in nature and no statistical comparisons are made
  • OLE studies tend to include patients who respond to treatment and exclude those who discontinue treatment for any reason. As such, evaluating long-term efficacy using continuous variables can be influenced by progressively smaller numbers of patients remaining in the study

CI=confidence interval; DAS28-ESR=erythrocyte sedimentation rate; SDAI=simplified disease activity index; ACR 50/70=American College of Rheumatology 50%/70% improvement criteria; QW=once weekly; Q2W=once every 2 weeks; SJC=swollen joint count; TJC=tender joint count.

See KEVZARA combination therapy safety data

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. 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 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

  • 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.

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 click here to 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).
  • polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

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. 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 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

  • 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.

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 click here to 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).
  • polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

References: 1. 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. 2. 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. 3. Kevzara [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc. 4. Genovese MC, Fleischmann R, Kivitz AJ, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate. Arthritis Rheumatol. 2015;67(6):1424-1437. 5. Fleischmann R, Adelsberg JV, Lin Y, et al. Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2017;69(2):277-290. 6. Data on file. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc. 7. Humira [prescribing information]. North Chicago, IL: AbbVie Inc. 8. Burmester GR, Strand V, Rubbert-Roth A, et al. Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. RMD Open. 2019;5(2):e001017. doi:10.1136/rmdopen-2019-001017. 9. 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. Supplementary appendix available at: https://academic.oup.com/rheumatology/article/62/10/3268/7023918#supplementary-data. Accessed November 9, 2023.

MAT-US-2303590-v2.0-09/2024
Last Updated: September 2024