KEVZARA delivered sustained, steroid-free remission at 1 year1
achieved sustained remission at Week 52 with KEVZARA 200 mg Q2W + 14-week corticosteroid (CS) taper compared to placebo Q2W + 52-week CS taper (10.3%)1
- The difference of 18% vs placebo was statistically significant (95% CI: 4.2, 31.8; P=0.0193)1
Sustained remission was defined as achievement of all four components of the composite endpoint: absence of signs and symptoms and CRP <10mg/L (disease remission)* achieved by Week 12; absence of disease flare† from Week 12 through Week 52; sustained reduction of CRP (<10 mg/L) from Week 12 through Week 52; and successful adherence to prednisone taper from Week 12 through Week 52.1,2
of patients (n=30/60) in the KEVZARA arm achieved successful adherence to prednisone taper from Week 12 through Week 52 compared with 24.1% of patients (n=14/58) in the placebo-controlled arm.1,2‡
‡Successful adherence to the prednisone taper from Week 12 through Week 52 is defined as patients who did not take rescue therapy from Week 12 through Week 52 and might include the use of any excess prednisone (beyond the per protocol CS tapering regimen) with a cumulative dose of ≤100 mg (or equivalent), such as those employed to manage AE not related to PMR. The cumulative dose of excess prednisone use was counted from baseline to Week 52.3
AE=adverse event; CI=confidence interval; CRP=C-reactive protein; CS=corticosteroid; PMR=polymyalgia rheumatica; Q2W=once every 2 weeks; SD=standard deviation.
KEVZARA demonstrated statistically significant sustained remission at Week 521,2
Primary Endpoint: Proportion of patients achieving sustained remission at Week 52
With sustained remission, patients achieved disease remission no later than Week 12 and maintained disease remission through Week 52
KEVZARA showed improvement across all components of sustained remission1,2
By Week 12, patients in the KEVZARA arm were receiving 3 mg of daily CSs while patients in the placebo-controlled arm were receiving 9 mg of daily CSs (per protocol, excluding rescue CSs)3
*Disease remission is defined as the resolution of signs and symptoms of PMR, and normalization of CRP (<10 mg/L).1,2
†Flare is defined as recurrence of signs and symptoms attributable to active PMR requiring an increase in corticosteroid dose, or elevation of ESR attributable to active PMR plus an increase in corticosteroid dose.1,2
§The status of normalization of CRP from Week 12 through Week 52 was determined based on the CRP values measured at Week 16, Week 20, Week 24, Week 32, Week 40 and Week 52. If there were 2 or more consecutive visits with CRP ≥10 mg/L, then it was categorized as no normalization of CRP.3
||Successful adherence to the prednisone taper from Week 12 through Week 52 is defined as patients who did not take rescue therapy from Week 12 through Week 52 and might include the use of any excess prednisone (beyond the per protocol CS tapering regimen) with a cumulative dose of ≤100 mg (or equivalent), such as those employed to manage AEs not related to PMR. The cumulative dose of excess prednisone use was counted from baseline to Week 52.3
AEs=adverse events; CRP=C-reactive protein; ESR=erythrocyte sedimentation rate.
Even when acute-phase reactants (CRP and ESR) were removed in a sensitivity analysis of the primary endpoint of sustained remission at 52 weeks, results were consistent with the primary analysis1,2:
• 31.7% patients achieved sustained remission in the KEVZARA 200 mg Q2W + 14-week CS taper arm¶
• 13.8% achieved sustained remission in the placebo + 52-week CS taper arm
¶Difference (95% CI): 17.9 (3.13, 32.61).
Steroid-sparing effect: Patients received a lower cumulative CS dose during the 52-week treatment period vs the comparator arm1,2
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- The median of the difference between the actual and expected cumulative CS dose based on the prednisone taper assigned was 0.0 mg in the KEVZARA arm vs 199 mg in the comparator arm2
- The mean [SD] difference between the actual and expected cumulative CS dose was 298 [589] mg in the KEVZARA arm vs 455 [548] mg in the placebo arm3
- More than 50% patients in the KEVZARA arm had the same actual and expected cumulative CS dose2
- Over the course of the study duration, patients in the KEVZARA 200 mg Q2W + 14-week CS taper arm received a mean daily dose of CSs of 3.2 mg/day# vs a mean daily dose of 7.2 mg/day in the CS + placebo Q2W arm3,4
KEVZARA helped improve sustained remission rates, while patients in the KEVZARA arm used less CSs1
• While the comparator arm used a 52-week CS taper consistent with the ACR/EULAR guidelines, the KEVZARA arm used a 14-week CS taper
#Cumulative dose of CS up to the end of treatment, including expected prednisone in tapering regimen over 14 weeks per protocol, add-on prednisone, used in rescue therapy and the use of commercial prednisone.1
Analysis of evaluable patients data limitations
- Analyses based on observed cases or evaluable patients are restricted to a subset of patients defined based on a post-randomization variable, leading to potentially biased comparisons between treatment arms and limiting the interpretability of the results
- It is difficult to determine whether any differences observed are due to the effects of the treatment or to differences in patient characteristics between the subsets of randomized patients in the two arms
ITT Analysis
Proportion of patients with no PMR signs and symptoms over 52 weeks5
Results are descriptive. No conclusions can be made as data were not multiplicity controlled. See additional limitations on evaluable patients above.
ITT=intention to treat.
Observed Case** Analysis
Proportion of patients with no PMR signs and symptoms over 52 weeks2,5
Results are descriptive. No definitive conclusions can be made as data were not multiplicity controlled. See additional limitations on evaluable patients above.
**Observed cases “N” refers to the number of patients who had PMR assessments at each visit, including PMR assessments performed after treatment discontinuation.
Proportion of patients at Week 52 with no PMR signs and symptoms and had not received rescue therapy
ITT Analysis
Results are descriptive. No definitive conclusions can be made as data were not multiplicity controlled. See additional limitations on evaluable patients above.
Observed Case Analysis††
Results are descriptive. No conclusions can be made as data were not multiplicity controlled. See additional limitations on evaluable patients above.
††The as-observed cases are based on patients with PMR assessments at each visit (PMR assessments after treatment discontinuation were not included), with the first assessment scheduled at Week 16 after completion of the predefined CS taper at Week 14 in the KEVZARA arm and Week 52 in the comparator arm.5
In an as-observed analysis of evaluable patients on treatment
Cumulative proportion‡‡ of patients who received rescue therapy5,7
Post hoc analysis. Results are descriptive. No conclusions can be made. See additional limitations on evaluable patients above.
‡‡Cumulative percentage; number of patients requiring rescue medication/total number of patients in the respective arm.5,7
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.
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:
- polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.
- 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.
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:
- polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.
- moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).
References: 1. KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc. 2. Spiera RF, Unizony S, Warrington KJ, et al. Sarilumab for relapse of polymyalgia rheumatica during glucocorticoid taper. N Engl J Med. 2023;389(14):1263-1272. 3. Data on file. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc. 4. 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 the European Congress of Rheumatology (EULAR); May 31-June 03, 2023; Milan, Italy. 5. Spiera RF, Unizony S, Warrington KJ, et al. Sarilumab for relapse of polymyalgia rheumatica during glucocorticoid taper. 2023;389(14):1263-1272. N Engl J Med. Supplementary appendix available at: https://www.nejm.org/doi/suppl/10.1056/NEJMoa2303452/suppl_file/nejmoa2303452_appendix.pdf. Accessed November 1, 2023. 6. 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 the Rheumatology Winter Clinical Symposium; February 15-18, 2023; Maui, HI. 7. Spiera R, Unizony S, Warrington KJ, et al. Resolution of PMR signs and symptoms in patients treated with sarilumab: a phase 3, multicenter, randomized, double blind, placebo controlled trial (SAPHYR) in relapsing PMR. Poster presented at the American College of Rheumatology Convergence; November 10-14, 2022; Philadelphia, PA.