KEVZARA: Clinical evidence
Knowledge of how a treatment impacts the underlying condition is important when evaluating the clinical value that it brings
KEVZARA clinical overview1
KEVZARA is the first and only biologic treatment approved by the US Food and Drug Administration (FDA) for adult patients with polymyalgia rheumatica (PMR), and a proven treatment for rheumatoid arthritis (RA).
KEVZARA is also FDA approved for use in patients who weigh 63 kg or greater with active polyarticular juvenile idiopathic arthritis (pJIA)
Talk to a Sanofi Market Access Account Director to learn more about this indication for KEVZARA.
KEVZARA mechanism of action
KEVZARA helps inhibit the effects of chronically elevated interleukin-6 (IL-6)1,2
KEVZARA is a fully human IL-6 receptor inhibitor that targets and binds with high affinity to soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), thereby inhibiting IL-6 signaling
The clinical significance of these findings is unknown.
*Following single-dose subcutaneous administration of sarilumab in patients with RA, absolute neutrophil counts decreased to the nadir between 3 and 4 days and thereafter recovered toward baseline.1
KEVZARA clinical trials
KEVZARA demonstrated efficacy and safety for the treatment of adult patients with PMR and as either a combination or monotherapy option for patients with RA.1 KEVZARA also demonstrated superiority as a monotherapy in a head-to-head RA trial with another biologic.3
PMR clinical trial
SAPHYR study
The SAPHYR trial was designed to evaluate the efficacy and safety of KEVZARA in patients with PMR.1,4
KEVZARA 200 mg + 14-week CS taper vs placebo + 52-week CS taper (N=118)*
KEVZARA and placebo were administered subcutaneously
| PRIMARY ENDPOINT |
| Proportion of patients with sustained remission at week 52; sustained remission was defined as achievement of all 4 of the following components: |
| Absence of signs and symptoms and C-reactive protein (CRP) <10 mg/L (disease remission†) no later than week 12 |
| Absence of disease flare from week 12 through week 52‡ |
| Sustained reduction of CRP (to <10 mg/L) from week 12 through week 52 |
| Successful adherence to prednisone taper from week 12 through week 52 |
| ADDITIONAL ENDPOINT |
| Proportion of patients with no PMR signs and symptoms over 52 weeks |
| Total cumulative CS dose over 52 weeks |
CS=corticosteroid; Q2W=every 2 weeks.
*One patient was randomized but not treated.
†Disease remission is defined as the resolution of signs and symptoms of PMR, and normalization of CRP (<10 mg/L).1 ‡Flare is defined as recurrence of signs and symptoms attributable to active PMR requiring an increase in CS dose, or elevation of erythrocyte sedimentation rate (ESR) attributable to active PMR plus an increase in CS dose.
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SAPHYR key inclusion criteria5
Participants must be aged ≥50 years
Diagnosis of PMR according to EULAR/ACR classification criteria
Participants must be on prednisone of at least 7.5 mg/day (or equivalent) and not exceeding 20 mg/day at screening and during the screening period
Participants were willing and able to take prednisone of 15 mg/day at randomization
Participants had a history of being treated for at least 8 weeks with prednisone ≥10 mg/day or equivalent
Participants must have had at least 1 episode of unequivocal PMR flare while attempting to taper prednisone at a dose that was ≥7.5 mg/day or equivalent within the past 12 weeks prior to screening
- Unequivocal symptoms of PMR flare included shoulder and/or hip girdle pain associated with inflammatory stiffness
Participants had ESR ≥30 mm/hour and/or CRP ≥10 mg/L associated with PMR disease activity within 12 weeks prior to screening
ACR=American College of Rheumatology; CRP=C-reactive protein; ESR=erythrocyte sedimentation rate; EULAR=European Alliance of Associations for Rheumatology.
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SAPHYR key exclusion criteria5
Diagnosis of giant cell arteritis (eg, persistent or recurrent localized headache, temporal artery or scalp tenderness, jaw claudication, extremity claudication, blurry or loss of vision, symptoms of stroke)
Diagnosis of active fibromyalgia
Concurrent RA or other inflammatory arthritis or other connective tissue diseases, such as but not limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing spondylitis
Concurrent diagnosis of rhabdomyolysis or neuropathic muscular diseases
Inadequately treated hypothyroidism
Organ transplant recipient
Therapeutic failure, including inadequate response or intolerance or contraindication to biological IL-6 antagonist
Any prior (within the defined period below) or concurrent use of immunosuppressive therapies, but not limited to any of the following:
- Janus kinase inhibitor within 4 weeks of baseline
- Alkylating agents including cyclophosphamide within 6 months of baseline
- Cell-depletion agents (e.g., anti-CD20) without evidence of recovery of B cells to baseline level
- TNF inhibitors within 2 to 8 weeks (etanercept within 2 weeks, infliximab, certolizumab, golimumab, or adalimumab within 8 weeks), or after at least 5 half-lives have elapsed, whichever was longer
- Abatacept within 8 weeks of baseline
- Anakinra within 1 week of baseline
- Cyclosporine, azathioprine, mycophenolate mofetil, or leflunomide within 4 weeks of baseline
Unstable MTX dose and/or MTX dose >15 mg/week within 3 months of baseline
Concurrent use of systemic corticosteroids for conditions other than PMR
Pregnant or breastfeeding woman
Participants with active or untreated latent tuberculosis
Participants with history of invasive opportunistic infections
Participants with fever associated with infection or chronic, persistent, or recurring infections requiring active treatment
Participants with uncontrolled diabetes mellitus
Participants with nonhealed or healing skin ulcers
Participants who received any live, attenuated vaccine within 3 months of baseline
Participants who were positive for hepatitis B, hepatitis C, and/or human immunodeficiency virus
Participants with a history of active or recurrent herpes zoster
Participants with a history of or prior articular or prosthetic joint infection
Prior or current history of malignancy
Participants who have had surgery within 4 weeks of screening or planned surgery during study
Participants with a history of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation
IL-6=interleukin-6; MTX=methotrexate; TNF=tumor necrosis factor.
Per protocol, the initial dose of CS for both groups was 15 mg/day for the first 2 weeks after randomization. Participants then followed different tapering regimens per assigned group.4
The proportion of patients achieving sustained remission at week 52 was higher in the KEVZARA arm compared with the placebo-controlled arm1
PMR signs, flares, and symptoms from SAPHYR
RA clinical trials: MOBILITY, TARGET, and MONARCH
Clinical response of adult patients with moderately to severely active RA to KEVZARA was studied across multiple clinical trials. Patients were diagnosed based on criteria established by the American College of Rheumatology (ACR).1
MOBILITY study
KEVZARA was studied in patients with moderately to severely active RA who had an inadequate clinical response to methotrexate (MTX) therapy
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MOBILITY study design1,2
After 16 weeks in MOBILITY, patients with an inadequate response could have been treated with open-label KEVZARA 200 mg every 2 weeks.
CCP=cyclic citrullinated peptide; hsCRP=high-sensitivity C-reactive protein; MTX=methotrexate; Q2W=every 2 weeks; R=randomized; RF=rheumatoid factor; SJC=swollen joint count; TJC=tender joint count.
ACR20 (24 weeks)
∆HAQ-DI (16 weeks)
∆mTSS (52 weeks)
Significant improvements in HAQ-DI1,2
In MOBILITY, nearly 50% of patients on KEVZARA 200 mg + MTX maintained clinically meaningful improvement in physical function through week 52.1,2*
*Minimal clinically important difference. HAQ-DI change from baseline ≥0.3 units.
KEVZARA demonstrated increased inhibition of radiographic joint damage progression—56% of patients with MTX-IR had no radiographic progression with KEVZARA at 52 weeks vs 39% of patients treated with placebo.1,2*†
*Defined as mean change from baseline in the van der Heijde-mTSS of ≤0.2
†Based on post-hoc comparisons of mean change in mTSS per treatment group. Week 52 analysis employs linear extrapolation method to impute missing or post-rescue data.2
TARGET study
KEVZARA was studied in patients who had an inadequate clinical response or intolerance to 1 or more tumor necrosis factor (TNF) inhibitors1,12
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TARGET study design1,12
DMARD=disease-modifying antirheumatic drug; hsCRP=high-sensitivity C-reactive protein; Q2W=every 2 weeks; R=randomized; SJC=swollen joint count; TJC=tender joint count; TNF=tumor necrosis factor.
ACR20 (24 weeks)
∆HAQ-DI (12 weeks)
MONARCH study: KEVZARA vs adalimumab head-to-head clinical trial in MTX-IR patients1,3
KEVZARA was studied in patients who were inappropriate for MTX therapy because of intolerance or inadequate response
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MONARCH study design1,3
ACR20/50/70=American College of Rheumatology 20%/50%/70% improvement criteria; CRP=C-reactive protein; DAS28-ESR=disease activity score 28-erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ-DI=Health Assessment Questionnaire–Disability Index; MTX=methotrexate; MTX-IR=methotrexate inadequate response; QW=once a week; Q2W=every 2 weeks; R=randomized; SJC=swollen joint count; TJC=tender joint count.
*The recommended dose of subcutaneous adalimumab is 40 mg Q2W. Some patients not taking concomitant MTX may derive additional benefit from increasing the subcutaneous dosing frequency to 40 mg QW; see adalimumab full Prescribing Information.
Given the limitations and context described, caution should be used when interpreting monotherapy data.
MONARCH additional study context1,3
- MONARCH data are not included in the KEVZARA US 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 Prescribing Information
Use of adalimumab
- Adalimumab and KEVZARA have different indications and can be used differently in clinical practice1,13
- Dose escalation from adalimumab 40 mg Q2W to 40 mg once a week (QW) was permitted after week 16 in patients who had not achieved at least 20% improvement in tender joint count (TJC) and swollen joint count (SJC). By week 24, dosing for 8.6% of patients on adalimumab was adjusted3
Study limitations1,2,6
- 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.
KEVZARA demonstrated disease activity improvements vs adalimumab
Significantly greater improvements in HAQ-DI were achieved with KEVZARA monotherapy vs adalimumab monotherapy at 24 weeks.3
KEVZARA safety profile in PMR and RA trials
PMR safety profile
THE MOST COMMON ADVERSE EVENTS (≥5%) OCCURRING IN PATIENTS IN THE SAPHYR STUDY1,4*
| ADVERSE EVENT, % (n) | KEVZARA 200 mg Q2W + 14-week CS taper (n=59) | Placebo Q2W + 52-week CS taper (n=58) |
| Infections and infestations | 37.3% (22) | 50% (29) |
| Neutropenia | 15.3% (9) | 0.0% |
| Leukopenia | 6.8% (4) | 0.0% |
| Constipation | 6.8% (4) | 0.0% |
| Myalgia | 6.8% (4) | 0.0% |
| Rash pruritic | 5.1% (3) | 0.0% |
| Fatigue | 5.1% (3) | 0.0% |
| Injection site pruritus | 5.1% (3) | 0.0% |
The incidence of serious infections was similar in the KEVZARA group (5.1%) compared with the placebo-controlled group (5.2%). Serious adverse reactions of neutropenia occurred in 2 patients (3.4%) in the KEVZARA group compared with none in the placebo group.1
In both cases of neutropenia, the participants had a neutrophil count <500/mm3 without any infections and resolved following permanent discontinuation of study drug.
The most common adverse reactions that resulted in permanent discontinuation of therapy with KEVZARA were neutropenia, which occurred in 3 patients (5.1%); infection (including COVID-19), which occurred in 3 patients (5.1%); intervertebral discitis (n=1), and pneumonia (n=1).
*Fifty-nine patients with PMR who were treated with KEVZARA were evaluated for safety in the 12-month, placebo-controlled Phase 3 clinical trial.1
RA safety profile
KEVZARA has an established safety profile as a combination therapy in RA.
COMMON ADVERSE REACTIONS DURING THE PLACEBO-CONTROLLED PERIOD OF THE RANDOMIZED TRIALS1*
| PREFERRED TERM | Placebo + DMARD(s) N=579 | KEVZARA 150 mg + DMARD(s) N=579 | KEVZARA 200 mg + DMARD(s) N=582 |
| Neutropenia | 0.2% | 7% | 10% |
| Alanine aminotransferase increased | 2% | 5% | 5% |
| Injection site erythema | 0.9% | 5% | 4% |
| Injection site pruritus | 0.2% | 2% | 2% |
| Upper respiratory tract infection | 2% | 4% | 3% |
| Urinary tract infection | 2% | 3% | 3% |
| Hypertriglyceridemia | 0.5% | 3% | 1% |
| Leukopenia | 0% | 0.9% | 2% |
A medically relevant adverse event occurring at an incidence of <2% in patients with RA treated with KEVZARA in controlled studies was oral herpes
Decrease in absolute neutrophil count was not associated with higher incidence of infections, including serious infections
In the long-term safety population, the overall rates of serious infections, gastrointestinal perforations, neutrophil counts, platelet counts, and lipid parameters were consistent with what was observed in the placebo-controlled trials
*Adverse events occurring in ≥2% of patients administered KEVZARA 200 mg or KEVZARA 150 mg + DMARD(s) and greater than those observed in patients on placebo + DMARD(s).
KEVZARA monotherapy safety was studied in 471 patients with more than 1700 patient-years of exposure. Mean exposure in the long-term safety population was 3.7 years (6.2 years maximum).17
KEVZARA safety profile as head-to-head monotherapy vs adalimumab
LONG-TERM MONOTHERAPY SAFETY INCLUDING MONARCH (MTX-IR) AND MONARCH LONG-TERM SAFETY POPULATIONS21*†
| RANDOMIZED, CONTROLLED POPULATION | Long-term | ||
| Adverse event | Adalimumab | KEVZARA | KEVZARA |
| Cumulative total | 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 deathll | 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) |
| Alanine aminotransferase | 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) |
MedDRA=Medical Dictionary for Regulatory Activities; MTX-IR=methotrexate inadequate response; nE=normalized event; OLE=open-label extension; Q2W=every 2 weeks; TEAE=treatment-emergent adverse event.
*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.3
†One hundred and eleven patients from the KEVZARA OLE study population were included in these long-term monotherapy safety data.20
‡One patient was randomized, but not treated, in the adalimumab group and was not included in the safety population.3
§TEAE period from the first treatment dose of 60 days after the last treatment dose.3
llIn the randomized trial, 1 patient in the KEVZARA group died of acute cardiac failure secondary to aortic dissection and papillary muscle rupture on day 36.15
¶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.3
#Protocol defined as ≥2 doses within 11 calendar days or within 6 days for adalimumab-treated patients who switched to weekly dosing.3
**Dyslipidemia was defined by standardized MedDRA query.3
222 patients (47.1%) were treated for >240 weeks (4.6 years)
Safety observations in the long-term population were generally consistent with those in the randomized, controlled population.1,21
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.3
Incidence rate of adverse events was generally stable over time, with no indication of increased incidence rate.1,21
Normalized event (nE)/100 patient-years is the exposure-adjusted event rate.22
Long-term safety
KEVZARA was studied in 2887 MTX-IR and TNF-IR patients with more than 10,000 patient-years of exposure19,20
Mean duration of treatment was 3.5 years (max 10.1 years), representing 10,007.6 cumulative patient-years of exposure
62 patients (2.1%) were treated for >480 weeks (9.2 years)
The incidence rate of adverse events was generally stable over time, with no indication of increased incidence rate in serious adverse events and serious infections1,21
In the long-term safety population, the rate of thromboembolic events (MedDRA high-level group term “embolism and thrombosis”) was 0.5 per 100 patient-years (as reported and evaluated post hoc; not a prespecified adverse event of special interest).15,22
Rate of deep vein thrombosis was 0.2 per 100 patient-years; rate of pulmonary embolism was 0.2 per 100 patient-years
MedDRA=Medical Dictionary for Regulatory Activities.
Dosing and administration1
Recommended dosage for RA
The recommended dosage of KEVZARA is 200 mg Q2W given as a subcutaneous injection. KEVZARA may be used as monotherapy or in combination with MTX or other conventional DMARDs. Reduce the dose to 150 mg Q2W for the management of neutropenia, thrombocytopenia, or elevated liver enzymes.
Recommended dosage for PMR
The recommended dosage of KEVZARA is 200 mg Q2W given as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids. KEVZARA can be used as monotherapy following discontinuation of corticosteroids. Discontinue KEVZARA if the patient develops neutropenia (using absolute neutrophil count results obtained at the end of the dosing interval), thrombocytopenia, or liver enzyme abnormalities.
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References: 1. KEVZARA. Prescribing information. Sanofi/Regeneron Pharmaceuticals, Inc.; 2023. 2. Genovese MC, Fleischmann R, Kivitz AJ, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a phase III study. Arthritis Rheumatol. 2015;67(6):1424-1437. doi:10.1002/art.39093 3. 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. doi:10.1136/annrheumdis-2016-210310 4. Data on file. Sanofi/Regeneron. SAPHYR CSR. Final report. November 15, 2021. 5. Evaluation of the efficacy and safety of sarilumab in patients with polymyalgia rheumatica (NCT03600818). ClinicalTrials.gov. Updated June 10, 2022. Accessed January 29, 2024. https://clinicaltrials.gov/ct2/show/NCT03600818 6. Data on file. Sanofi/Regeneron. SAPHYR EFC15160. Final report. November 15, 2021. 7. Dasgupta B, Praestgaard A, Fiore S, et al. Sustained remission from weeks 16 to 52 and weeks 24 to 52 in patients treated with sarilumab: post-hoc analysis of SAPHYR trial in patients with polymyalgia rheumatica. Poster presented at: European Congress of Rheumatology (EULAR) 2023; May 31-June 3, 2023; Milan, Italy. POS0715. 8. Spiera R, Unizony S, Warrington KJ, et al. Glucocorticoid (GC)-free resolution of polymyalgia rheumatica (PMR) signs and symptoms in patients treated with sarilumab with history of flare: analysis from SAPHYR. Poster presented at: Rheumatology Winter Clinical Symposium (RWCS) 2023; February 15-18, 2023; Maui, Hawaii. 9. Duckworth H. ACR score: What does an ACR score measure? Rheumatoid Arthritis Support Network. September 25, 2018. Accessed March 1, 2024. https://www.rheumatoidarthritis.org/treatment/acr-score/ 10. Gossec L. Chapter 5- Monitoring of disease and treatment of patients with rheumatic disease. In: Atzeni F, Masala IF, Aletaha D, Lee M, Baraliakos X, eds. Handbook of Systemic Autoimmune Diseases Volume 15: Surgery in Rheumatic and Musculoskeletal Disease. Elsevier; 2018:97-125. 11. Spasovski D. Some comparation aspect of determination of overall scoring indexes between osteoarticular scores, Sharp’s radiographic indexes in patients with rheumatoid arthritis. Clin Med Rev Case Rep. 2015;2(9):CMRCR-2-056. doi:10.23937/2378-3656/1410056 12. Fleischmann R, van Adelsberg J, 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. doi:10.1002/art.39944 13. Humira. Prescribing information. AbbVie Inc.; 2024. 14. The Merck Manual. Professional version. 2022. https://www.merckmanuals.com/professional 15. Data on file. Sanofi/Regeneron. Summary of TEAEs—sarilumab combination population (pools 1 and 2). April 2023. 16. Data on file. Sanofi/Regeneron. ISR statement-data source. June 2021. 17. Data on file. Sanofi/Regeneron. Integrated summary of safety appendix 1.4. 2018. 18. Data on file. Sanofi/Regeneron. Summary of treatment emergent adverse events-sarilumab MONARCH and monotherapy population. 19. Data on file. Sanofi/Regeneron. ISS: Appendix 1.3. June 2019. 20. Data on file. Sanofi/Regeneron. Integrated summary. October 2019. 21. Data on file. Sanofi/Regeneron. EXTEND CSR. January 2016. 22. 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. doi:10.1093/rheumatology/kead062
INDICATIONS
KEVZARA® (sarilumab) is indicated for treatment of adult patients with:
- 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).
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
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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 click here to see full Prescribing Information, including Boxed WARNING.
INDICATIONS
KEVZARA® (sarilumab) is indicated for treatment of adult patients with:
- 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).
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 click here to see full Prescribing Information, including Boxed WARNING.
INDICATIONS
KEVZARA® (sarilumab) is indicated for treatment of adult patients with:
- 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).
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 click here to see full Prescribing Information, including Boxed WARNING.
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