The MONARCH head-to-head superiority trial measured effect on disease activity, physical function, and clinical response with KEVZARA vs adalimumab1
After Week 16 in MOBILITY, patients with an inadequate response could have been treated with open-label KEVZARA 200 mg every 2 weeks.2,3
CO-PRIMARY ENDPOINT DATA2,3
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
CO-PRIMARY ENDPOINT DATA2,4
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<0.0001.2,3
†P<0.001.3
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.
- 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
- 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
- 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
- Adalimumab and KEVZARA have different indications and can be used differently in clinical practice3,8
- 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
- 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
MONARCH monotherapy study design, context, and limitations1
MONARCH study design
Primary endpoint data5‡
‡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 context1,2
Use of adalimumab
Study limitations1,2,6
Given the limitations and context described above, caution should be used when interpreting monotherapy data.
CRP=C-reactive protein; DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; ESR=Erythrocyte Sedimentation Rate; FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy-Fatigue Scale; QW=once weekly.
Expert perspectives
Watch Dr Suzanne Gharib share her clinical expertise, discussing the importance of head-to-head monotherapy data.
- 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.
- 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.
- 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.
- 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.
- 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.
TRANSCRIPT
[Introduction. 00:00-00:20]
Hi, I’m Suzanne Gharib. I’m a rheumatologist in private practice in South Charleston, West Virginia. I have a special interest in research doing rheumatoid arthritis research on a routine basis, and have a very busy clinical practice, as well as an affiliation with Mon General Hospital in Morgantown, West Virginia.
[Considering monotherapy or switching from MTX. 00:20-01:20]
“What inputs do you leverage when considering monotherapy or switching a patient from methotrexate?”
So, when I see a patient who’s not doing well on methotrexate, and I’m considering either switching them or I have somebody on combination therapy, and I’m considering dropping the methotrexate and using the biologic as monotherapy, there’s a few things I consider. One of them is the head-to-head trial data. I think that really helps to guide treatment decisions in rheumatoid arthritis.
Now we, as rheumatologists, tend to ask for head-to-head trials. But we don’t always rely on the information as much as we ought to. I think it’s incredibly important that we review the available clinical trial data, especially if we are considering monotherapy options. So you really need to see the head-to-head results and particularly superiority data.
And one example of that is the MONARCH Trial, which has good data and a head-to-head type setting. And it’s important superiority data.1
[KEVZARA Indication and Safety. 01:20-01:54]
KEVZARA is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis, who’ve had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. Patients treated with KEVZARA are at an increased risk for developing serious infections that may lead to hospitalization or death. Avoid the use of KEVZARA in patients with an active infection, and closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. This will be discussed more, along with additional important safety information, later in the video.2
[Therapeutic optimization for patients with RA. 01:54-02:39]
So, I think if you asked the average rheumatologist, “How many patients are on monotherapy?” they would guess one out of three. I would have said the same, until I saw some recent claims data that says it’s closer to 47 percent.
I believe we have this perception of, “oh patients take exactly what we tell them to take.” And that’s just not reality. What we find on claims data is about half of biologic or synthetic DMARD prescriptions are, in fact, for monotherapy. And the reasons for that are varied. But many patients are either unable or unwilling to use methotrexate for a variety of reasons. So as a healthcare provider, it’s important to select a treatment option that has strong results as both combination therapy, or monotherapy, in the event that patients don’t take their methotrexate.
[Therapeutic changes for patients with RA. 02:39-03:21]
So, when we start patients on methotrexate, do we ever wonder how quickly or how often do they switch—or even another biologic, how quickly do they switch? There’s a lot of data about that. And the looks of it is about half of patients who are initially prescribed methotrexate alone will either switch to a biologic, or add a biologic within a year. Unfortunately, if you follow this graphic, that switch happens recurrently.7,8
That is not necessarily the best thing for the patient. It really highlights the importance of choosing the appropriate therapy, for the appropriate patients, in the appropriate time. And that is really getting to know your patient, their comorbidities, and determining the best agent on that basis.
[Experience treating patients with RA. 03:21-04:15]
When it comes to my patients, I have quite a few on monotherapy. I would say anywhere from 30 to 50 percent. And what drives that is my usual goal is actually to get patients to monotherapy if at all possible. And most patients do not want to take multiple medications.
When I’m prescribing a new therapy, I think it’s incredibly important to consider, not just in the moment, but down the line, can patients move to monotherapy rather than combination therapy?
Traditionally, in RA, we use combination therapy. But we know the data is what the data is. Patients frequently skip medications, will choose to take one or the other. So, it’s incredibly important that when we choose a new biologic or small molecule, that we choose something that has strong results and good delivery as a monotherapy. That gives patients that option in the future.1
[Considering KEVZARA for monotherapy. 04:15-04:46]
When I have a patient who’s not tolerating methotrexate, or has concerns and doesn’t want to take it, and I’m considering monotherapy, one of the biologics I consider strongly is KEVZARA.2
KEVZARA gives strong results versus adalimumab in the MONARCH Trial, making it a good option for my patients interested in monotherapy.1
You can find detailed information about the clinical trial program for KEVZARA, including MONARCH, on the head-to-head monotherapy page of this website.
Please see the following Important Safety Information.
INDICATION
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).
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:
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
ADVERSE REACTIONS
DRUG INTERACTIONS
USE IN SPECIFIC POPULATIONS
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.
Greater improvement in disease activity vs adalimumab1
KEVZARA monotherapy was superior to adalimumab monotherapy in meeting primary endpoint of mean change from baseline to Week 24 in DAS28-ESR.1
49%
greater improvement in DAS28-ESR
than adalimumab at Week 241
MONARCH (MTX-IR) Change in DAS28-ESR at Week 241
IIDifference: -1.08 (95% CI: -1.36 to -0.79).1
KEVZARA patients achieved low disease activity (DAS28-ESR <2.6) vs adalimumab monotherapy1
(26.6% vs 7.0%; P<0.0001)
CI=confidence interval; DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; LS=least squares; MTX-IR=methotrexate inadequate response; Q2W=once every 2 weeks; SE=standard error.
Improved physical function vs adalimumab1
Significantly greater improvements in HAQ-DI were achieved with KEVZARA monotherapy vs adalimumab monotherapy through Week 24.1
42%
greater improvement in HAQ-DI
vs adalimumab at Week 241
MONARCH (MTX-IR): Change from baseline in HAQ-DI at Week 241
Greater clinical response vs adalimumab1
Significantly more patients achieved ACR responses with KEVZARA monotherapy vs adalimumab monotherapy through Week 24.1
MONARCH (MTX-IR): ACR response at Week 241
¶P<0.01.1
ACR50=American College of Rheumatology 50% improvement criteria; ACR70=American College of Rheumatology 70% improvement criteria; MTX-IR=methotrexate inadequate response.
More patients achieved greater control of disease activity with KEVZARA vs adalimumab1
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:
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:
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).
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