KEVZARA
EFFICACY
KEVZARA demonstrated rapid, sustained, consistent improvements in clinical response across multiple patient populations.1,2
EVALUATED IN MTX-IR AND TNF-IR PATIENTS IN COMBINATION WITH MTX/DMARD(s)
KEVZARA + MTX/DMARD(s) studied in 2 pivotal trials5,6
From week 16 onward in MOBILITY and from week 12 onward in TARGET, rescue treatment with open-label KEVZARA 200 mg q2w was permitted in patients with lack of efficacy, defined as ≥20% improvement from baseline in SJC or TJC for 2 consecutive visits.5,6
MTX-IR=methotrexate inadequate response; DMARDs=disease-modifying antirheumatic drugs;
hsCRP=high-sensitivity C-reactive protein; anti-CCP=anti-cyclic citrullinated peptide; RF=rheumatoid factor; q2w=once every 2 weeks; ACR20=American College of Rheumatology 20% improvement criteria; HAQ-DI=Health Assessment Questionnaire-Disability Index; mTSS=modified Total Sharp Score; SJC=swollen joint count; TJC=tender joint count.
KEVZARA + MTX/DMARD(s) SAFETY AND EFFICACY EVALUATED OVER TIME
KEVZARA + MTX/DMARD(s) studied in 2 pivotal trials5,6
- Long-term efficacy was evaluated in adult patients who completed MOBILITY or TARGET and subsequently enrolled in EXTEND OLE7
- Long-term safety was evaluated in all 2887 adult patients who received ≥1 dose of KEVZARA in combination with DMARD(s)7
EXTEND OPEN-LABEL EXTENSION (OLE) STUDY LIMITATIONS AND ADDITIONAL STUDY CONTEXT
- These data are not included in the US Prescribing Information. Data presented are truthful and not misleading
- Open-label extension studies tend to include patients who respond to treatment and exclude those who discontinue treatment for any reason. As such, evaluating long-term efficacy using continuous variables can be influenced by progressively smaller numbers of patients remaining in the study
- Data presented are descriptive in nature, and no statistical comparisons are made
- Clinical data were analyzed based on all available data as observed
LONG-TERM SAFETY ANALYSIS
- This was a comprehensive safety analysis from pooled studies of patients who received at least 1 dose of sarilumab in combination with DMARD(s) as of last data analysis on January 15, 2018
LONG-TERM EFFICACY ANALYSIS
- Efficacy assessments in this analysis did not include all of the primary endpoints from the placebo-controlled period of the pivotal trials analyzed
- For analysis of no radiographic progression, linear extrapolation was used to impute missing data. Patients with missing data after the imputation were considered progressors
Given the limitations and context described above, caution should be used in interpreting these data.
- * These 2 studies were discontinued due to low enrollment.9,11
- † Patients participating in the EXTEND OLE trial received KEVZARA 200 mg regardless of prior treatment in the placebo-controlled trials, except for patients who were previously dose-reduced to KEVZARA 150 mg due to safety issues, who continued on KEVZARA 150 mg.7,12
- ‡ Patients in the EASY OLE study received KEVZARA 150 mg regardless of their prior treatment.14
KEVZARA STUDIED AS MONOTHERAPY
MONARCH
A randomized, double-blind, double-dummy phase 3 superiority study to evaluate the efficacy and safety of KEVZARA monotherapy vs adalimumab monotherapy16*†
MONARCH ADDITIONAL STUDY CONTEXT
- MONARCH data are not included in the KEVZARA 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 USPI
USE OF ADALIMUMAB
- Adalimumab and KEVZARA have different indications and can be used differently in clinical practice
- Dose escalation from adalimumab 40 mg q2w to 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 adjusted
STUDY LIMITATIONS (MONARCH)
- KEVZARA and adalimumab can be used as monotherapy or in combination with nonbiologic DMARD(s). 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 these data.
- * 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.16
- † After week 16, dose escalation to adalimumab qw was permitted for patients who did not achieve ≥20% improvement in TJC and SJC.16
- ‡ The recommended dose of adalimumab SC is 40 mg q2w. Some patients not taking concomitant MTX may derive additional benefit from increasing the SC dosing frequency to 40 mg qw; see adalimumab full Prescribing Information.17
KEVZARA MONOTHERAPY EVALUATED OVER TIME
MONARCH
A randomized, double-blind, double-dummy phase 3 superiority study to evaluate the efficacy and safety of KEVZARA monotherapy vs adalimumab monotherapy16*†
MONARCH OLE
An extension designed to assess the safety and efficacy of long-term continuous KEVZARA monotherapy and switching from adalimumab monotherapy to KEVZARA monotherapy21
MONARCH OPEN-LABEL EXTENSION (OLE) STUDY LIMITATIONS AND ADDITIONAL STUDY CONTEXT
- These data are not included in the USPI. Data presented are truthful and not misleading
- Long-term safety analysis included all patients who received at least 1 dose of KEVZARA monotherapy as of last data analysis on January 15, 2018
- Analysis of clinical data were based on all available data as observed
- Data presented are descriptive in nature and no statistical comparisons are made
- Open-label extension studies tend to include patients who respond to treatment and exclude those who discontinue treatment for any reason. As such, evaluating long-term efficacy using continuous variables can be influenced by progressively smaller numbers of patients remaining in study
Given the limitations and context described above, caution should be used in interpreting these data.
- * 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.16
- † After week 16, dose escalation to adalimumab QW was permitted for patients who did not achieve ≥20% improvement in TJC and SJC.16
- ‡ The recommended dose of adalimumab SC is 40 mg q2w. Some patients not taking concomitant MTX may derive additional benefit from increasing the SC dosing frequency to 40 mg qw; see adalimumab full Prescribing Information.17
COMBINATION THERAPY
demonstrated rapid, sustained, consistent clinical response
ACR20 clinical response was observed in MTX-IR and TNF-IR patients as early as 2 weeks in MOBILITY and as quickly as 4 weeks in TARGET after the first dose.3,4
- *P<0.0001;†P<0.01.
- ‡DMARD(s) in TARGET include MTX, sulfasalazine, leflunomide, and/or hydroxychloroquine.
- §P<0.0001, P value is for descriptive purposes only and is not adjusted for multiplicity.
- ||P<0.0001.
Significant improvements in
HAQ-DI
OF MTX-IR PATIENTS MAINTAINED CLINICALLY MEANINGFUL IMPROVEMENT IN PHYSICAL FUNCTION THROUGH WEEK 52 WITH KEVZARA 200 mg + MTX5*
[Week 16: KEVZARA 200 mg + MTX: 57% (229/399) vs placebo + MTX: 42% (169/398); Week 52: KEVZARA 200 mg + MTX: 48% (190/399) vs placebo + MTX: 26% (104/398)]
- *Minimal clinically important difference. HAQ-DI change from baseline ≥0.3 units.
- ITT=intent to treat.
More patients achieved low
disease activity with KEVZARA
Significantly more MTX-IR and TNF-IR patients achieved DAS28-CRP <2.6 with KEVZARA vs placebo1,5
- DAS28-CRP=disease activity score 28-C-reactive protein.
56% OF MTX-IR PATIENTS HAD NO RADIOGRAPHIC PROGRESSION WITH KEVZARA AT 52 WEEKS vs 39% OF PATIENTS TREATED WITH PLACEBO1*
AT WEEK 521,5
greater inhibition of joint damage progression
with KEVZARA 200 mg + MTX vs placebo + MTX
- *Defined as mean change from baseline in the van der Heijde-mTSS of ≤0.
- †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.1
LONG-TERM COMBINATION THERAPY
KEVZARA + MTX/DMARD(s) SAFETY
AND EFFICACY EVALUATED OVER TIME
- Long-term efficacy was evaluated in adult patients who completed MOBILITY or TARGET and subsequently enrolled in EXTEND OLE7
- Long-term safety was evaluated in all 2887 adult patients who received ≥1 dose of KEVZARA in combination with DMARD(s)7
EXTEND OPEN-LABEL EXTENSION (OLE) STUDY LIMITATIONS AND ADDITIONAL STUDY CONTEXT
- These data are not included in the US Prescribing Information. Data presented are truthful and not misleading
- Open-label extension studies tend to include patients who respond to treatment and exclude those who discontinue treatment for any reason. As such, evaluating long-term efficacy using continuous variables can be influenced by progressively smaller numbers of patients remaining in the study
- Data presented are descriptive in nature, and no statistical comparisons are made
- Clinical data were analyzed based on all available data as observed
LONG-TERM SAFETY ANALYSIS
- This was a comprehensive safety analysis from pooled studies of patients who received at least 1 dose of sarilumab in combination with DMARD(s) as of last data analysis on January 15, 2018
LONG-TERM EFFICACY ANALYSIS
- Efficacy assessments in this analysis did not include all of the primary endpoints from the placebo-controlled period of the pivotal trials analyzed
- For analysis of no radiographic progression, linear extrapolation was used to impute missing data. Patients with missing data after the imputation were considered progressors
Given the limitations and context described above, caution should be used in interpreting these data.
- * These 2 studies were discontinued due to low enrollment.9,11
- † Patients participating in the EXTEND OLE trial received KEVZARA 200 mg regardless of prior treatment in the placebo-controlled trials, except for patients who were previously dose-reduced to KEVZARA 150 mg due to safety issues, who continued on KEVZARA 150 mg.7,12
- ‡ Patients in the EASY OLE study received KEVZARA 150 mg regardless of their prior treatment.13
OPEN-LABEL EXTENSION DATA
Clinical Response Over 5 Years
These data should be interpreted with caution. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
OPEN-LABEL EXTENSION DATA
HAQ-DI OVER 5 YEARS
These data should be interpreted with caution. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
Data in patients who received initial treatment with KEVZARA compared with those who initially received placebo.
mobility extend3,14,15
This analysis has not been performed for the TNF-IR population.
- *Mean HAQ-DI scores were calculated based on observed cases, without imputation of missing data.
MEAN HAQ-DI WAS MEASURED IN PATIENTS WHO
CONTINUED TREATMENT WITH KEVZARA FOR UP TO 5 YEARS3,14,15
OPEN-LABEL EXTENSION DATA
DAS28-CRP OVER 5 YEARS
These data should be interpreted with caution. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
Data in patients who received initial treatment with KEVZARA compared with those who initially received placebo.
OPEN-LABEL EXTENSION DATA
INHIBITION OF RADIOGRAPHIC PROGRESSION OVER 5 YEARS
These data should be interpreted with caution. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
Data in patients who received initial treatment with KEVZARA compared with those who initially received placebo.
mobility extend7
- *For the OLE analysis, no radiographic progression was defined as an increase from baseline in mTSS of ≤0.5; in the MOBILITY study, no radiographic progression was described as an increase from baseline in mTSS of ≤0.0. No clinical assessments were made between weeks 148, 196, and 244. For analysis of no radiographic progression, linear extrapolation was used to impute missing data. Patients with missing data after the imputation were considered progressors.5,7,15
INHIBITION OF STRUCTURAL PROGRESSION WAS MEASURED IN PATIENTS WHO
CONTINUED TREATMENT WITH KEVZARA FOR UP TO 5 YEARS7
MONOTHERAPY
KEVZARA STUDIED AS
MONOTHERAPY
MONARCH
A randomized, double-blind, double-dummy phase 3 superiority study to evaluate the efficacy and safety of KEVZARA monotherapy vs adalimumab monotherapy16*†
MONARCH ADDITIONAL STUDY CONTEXT
- MONARCH data are not included in the KEVZARA 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 USPI
USE OF ADALIMUMAB
- Adalimumab and KEVZARA have different indications and can be used differently in clinical practice
- Dose escalation from adalimumab 40 mg q2w to 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 adjusted
STUDY LIMITATIONS (MONARCH)
- KEVZARA and adalimumab can be used as monotherapy or in combination with nonbiologic DMARD(s). 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 these data.
- *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.16
- †After week 16, dose escalation to adalimumab qw was permitted for patients who did not achieve ≥20% improvement in TJC and SJC.16
- ‡The recommended dose of adalimumab SC is 40 mg q2w. Some patients not taking concomitant MTX may derive additional benefit from increasing the SC dosing frequency to 40 mg qw; see adalimumab full Prescribing Information.17
GREATER IMPROVEMENT IN DISEASE ACTIVITY vs ADALIMUMAB
KEVZARA monotherapy was superior to adalimumab monotherapy in meeting primary endpoint of mean change from baseline to week 24 in DAS28-ESR.16
greater improvement in DAS28-ESR
than adalimumab at week 2416
at week 2416
- *Difference: -1.08 (95% CI: -1.36 to -0.79).
KEVZARA patients achieved low disease activity (DAS28-ESR <2.6) vs adalimumab monotherapy
(26.6% vs 7.0%; P<0.0001)16
IMPROVED PHYSICAL FUNCTION vs ADALIMUMAB
Significantly greater improvements in HAQ-DI were achieved with KEVZARA monotherapy vs adalimumab monotherapy at 24 weeks.16
greater improvement in HAQ-DI
vs adalimumab at week 2416
Change from baseline
in HAQ-DI at week 2416
PROVIDED GREATER CLINICAL
RESPONSE vs ADALIMUMAB
Significantly more patients achieved ACR responses with KEVZARA monotherapy vs adalimumab monotherapy through week 24.16
ACR Responses at week 2416
- *P<0.01.
More patients achieved greated control of disease activity
with KEVZARA vs adalimumab16
Control of IL-6–related signs
and symptoms: CRP AND MORNING
STIFFNESS
RAPIDLY NORMALIZED CRP LEVELS3,4,16
CRP levels returned to normal (<10 mg/L) as early as 2 weeks after the first dose of KEVZARA.1,18
CRP was studied as part of ACR20/50/70 response endpoints in MOBILITY, TARGET, and MONARCH1,16*
- *Not a prespecified endpoint.
CHANGE IN MORNING STIFFNESS19,20
Morning stiffness was not assessed in MOBILITY.
CHANGES IN IL-6–RELATED SIGNS AND SYMPTOMS: PAIN
REDUCTIONS IN PAIN1,16
LONG-TERM MONOTHERAPY
KEVZARA MONOTHERAPY EVALUATED OVER TIME
MONARCH
A randomized, double-blind, double-dummy phase 3 superiority study to evaluate the efficacy and safety of KEVZARA monotherapy vs adalimumab monotherapy16*†
MONARCH OLE
An extension designed to assess the safety and efficacy of long-term continuous KEVZARA monotherapy and switching from adalimumab monotherapy to KEVZARA monotherapy21
MONARCH OPEN-LABEL EXTENSION (OLE) STUDY LIMITATIONS AND ADDITIONAL STUDY CONTEXT
- These data are not included in the USPI. Data presented are truthful and not misleading
- Long-term safety analysis included all patients who received at least 1 dose of KEVZARA monotherapy as of last data analysis on January 15, 2018
- Analysis of clinical data were based on all available data as observed
- Data presented are descriptive in nature and no statistical comparisons are made
- Open-label extension studies tend to include patients who respond to treatment and exclude those who discontinue treatment for any reason. As such, evaluating long-term efficacy using continuous variables can be influenced by progressively smaller numbers of patients remaining in study
Given the limitations and context described above, caution should be used in interpreting these data.
- *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.16
- †After week 16, dose escalation to adalimumab QW was permitted for patients who did not achieve ≥20% improvement in TJC and SJC.16
- ‡The recommended dose of adalimumab SC is 40 mg q2w. Some patients not taking concomitant MTX may derive additional benefit from increasing the SC dosing frequency to 40 mg qw; see adalimumab full Prescribing Information.17
MONARCH OPEN-LABEL EXTENSION DATA
CHANGE IN Disease Activity
These data should be interpreted with caution. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
baseline in DAS28-ESR21
Changes in disease activity were measured in both patients who continued treatment with KEVZARA monotherapy and in those who switched treatment from adalimumab to KEVZARA21
MONARCH OPEN-LABEL EXTENSION DATA
IMPROVEMENT IN PHYSICAL FUNCTION
These data should be interpreted with caution. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
MONARCH OPEN-LABEL EXTENSION DATA
OBSERVED ACR clinical response
These data should be interpreted with caution. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
IN OPEN-LABEL EXTENSION (OLE)21
- *ACR response is based on change from original study baseline and not OLE baseline.
Clinical response (ACR20/50/70) was measured in both patients who continued treatment with KEVZARA monotherapy and in those who switched treatment from adalimumab to KEVZARA
MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inadequate response or intolerant;
ACR20=American College of Rheumatology 20% improvement score; ACR50=American College of Rheumatology 50% improvement score; ACR70=American College of Rheumatology 70% improvement score; ITT=intent to treat;
DAS28-CRP=disease activity score 28-C-reactive protein; mTSS=modified total Sharp score; DMARDs=disease-modifying antirheumatic drugs; HAQ-DI=Health Assessment Questionnaire-Disability Index;
q2w=every 2 weeks.
References:
- KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc.
- Data on file, Sanofi/Regeneron. Integrated summary. April 1, 2017.
- Data on file, Sanofi/Regeneron. MOBILITY CSR data. August 2019.
- Data on file, Sanofi/Regeneron. TARGET CSR data. August 2019.
- 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.
- Fleischmann R, van Adelsberg J, Lin Y, et al. Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active RA and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2017;69(2):277-290.
- Data on file, Sanofi/Regeneron. EULAR poster SAT0172. June 2018.
- NIH. To evaluate the safety of SAR153191 (REGN88) and tocilizumab added to other RA drugs in patients with RA who are not responding to or intolerant of anti-TNF therapy (SARIL-RA-ASCERTAIN). ClinicalTrials.gov study NCT01768572. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01768572. Accessed July 27, 2019.
- NIH. Effect of SAR153191 (REGN88) with methotrexate in patients with active rheumatoid arthritis who failed TNF-α _blockers. https://clinicaltrials.gov/ct2/show/NCT01217814. Accessed July 27, 2019.
- Kivitz A, Baret-Cormel L, van Hoogstraten H, et al. Usability and patient preference phase 3 study of the sarilumab pen in patients with active moderate-to-severe rheumatoid arthritis. Rheumatol Ther. 2018;5(1):231-242.
- NIH. An evaluation of sarilumab plus methotrexate compared to etanercept plus methotrexate in RA patients not responding to adalimumab plus methotrexate (RA-COMPARE). https://clinicaltrials.gov/ct2/show/NCT01764997. Accessed July 27, 2019.
- NIH. Long term evaluation of sarilumab in rheumatoid arthritis patients (SARIL-RA EXTEND). https://clinicaltrials.gov/ct2/show/NCT01146652. Accessed July 27, 2019.
- Data on file, Sanofi/Regeneron. EXTEND CSR_interim analysis. January 2016.
- Data on file, Sanofi/Regeneron. MOBILITY Assessment of long term efficacy: EFC11072-LTS11210. 2017.
- Genovese MC, van der Heijde D, Lin Y, et al. Long-term safety and efficacy of sarilumab plus methotrexate on disease activity, physical function and radiographic progression: 5 years of sarilumab plus methotrexate treatment. RMD Open. 2019;5:e000887. doi:10.1136/rmdopen-2018-0008871.
- 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.
- Humira [package insert]. North Chicago, IL: AbbVie Inc; 2019.
- Center for Devices and Radiological Health. Guidance for industry and FDA staff: review criteria for assessment of c-reactive protein (CRP), high sensitivity c-reactive protein (hsCRP) and cardiac c-reactive protein (cCRP) assays. http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm071017.pdf. Accessed July 27, 2019.
- Strand V, Reaney M, Chen CI, et al. Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors. RMD Open. 2017;3(1):e0004:doi:10.1136/rmdopen-2016-000416.
- Strand V, Gossec L, Proudfoot CWJ, et al. Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis. Arthritis Res Ther. 2018;20(1):129. doi:10.1186/s13075-018-1614-z.
- Data on file, Sanofi/Regeneron. Burmester poster SAT0183. June 2018.