KEVZARA EFFICACY
Head-to-Head
Monotherapy and OLE
Mobility (MTX-ir) Study Design1
- *P<0.0001.
After week 16 in MOBILITY, patients with an inadequate response could have been treated with open-label KEVZARA 200 mg every 2 weeks.1
CO-PRIMARY ENDPOINTS1-3
ACR20 response at week 24: Patients achieved 66%* with KEVZARA 200 mg + MTX compared to 33% with placebo + MTX
ΔHAQ-DI at week 16: -0.58* with KEVZARA 200 mg + MTX compared to -0.30 with placebo + MTX
ΔmTSS from baseline at week 52: 0.25 with KEVZARA 200 mg vs 2.78 with placebo*: KEVZARA 200 mg + MTX provided an absolute difference of -2.52 units (CI: -3.38, -1.66) in mean ΔmTSS relative to placebo + MTX
TARGET (TNF-IR) Study Design1
- *P<0.0001; †P<0.001.
CO-PRIMARY ENDPOINT DATA (TNF-IR)1-3
ACR20 response at week 24: Patients achieved 61%* with KEVZARA 200 mg + DMARD(s) compared to 34% with placebo + DMARD(s)
ΔHAQ-DI at week 12: -0.49† with KEVZARA 200 mg + DMARD(s) compared to -0.29 with placebo + DMARD(s)
Head-to-Head Monotherapy and OLE
RELEVANT TRIALS: MONARCH, MONARCH OPEN-LABEL EXTENSION
Pivotal Trial Study Designs
(Monotherapy)
MONARCH STUDY DESIGN: A 24-week, randomized, double-blind, double-dummy, phase 3 superiority study to evaluate the efficacy and safety of KEVZARA 200 mg q2w monotherapy (n=184) vs adalimumab 40 mg q2w monotherapy (n=185) in patients who should not continue treatment with MTX due to intolerance or inadequate response.*†‡ The primary endpoint was ΔDAS28-ESR; secondary endpoints included ΔDAS28-ESR <2.6, ACR20/50/70, ΔDAS28-CRP, ΔHAQ-DI.1
PRIMARY ENDPOINT DATA1
- Change from baseline DAS28-ESR at 24 weeks: -3.28§ with KEVZARA 200 mg q2w monotherapy compared to -2.20 with adalimumab 40 mg q2w monotherapy
- The safety profiles of KEVZARA and adalimumab were generally comparable except for neutropenia and injection site erythema for KEVZARA and headache and RA for adalimumab
- *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; †After week 16, dose escalation to adalimumab qw was permitted for patients who did not achieve ≥20% improvement in TJC and SJC; ‡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.1,2; §P<0.0001; difference: -1.08 (95% CI: -1.36 to -0.79).1
- q2w=once every 2 weeks; MTX=methotrexate; DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; ACR20=American College of Rheumatology 20% improvement criteria; DAS28-CRP=disease activity score 28-C-reactive protein; HAQ-DI=Health Assessment Questionnaire-Disability Index; ITT=intent to treat; qw=once daily; TJC=tender joint count; SJC=swollen joint count; SC=subcutaneous.
References: 1. Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847. 2. Humira [package insert]. North Chicago, IL: AbbVie Inc; 2019.
MONARCH ADDITIONAL STUDY CONTEXT
- MONARCH data are not included in the KEVZARA US full Prescribing Information
- DAS28-ESR and FACIT-Fatigue were endpoints in MONARCH; however, there are no DAS28-ESR or FACIT-Fatigue data in the KEVZARA US full Prescribing Information
USE OF ADALIMUMAB
- Adalimumab and KEVZARA have different indications and can be used differently in clinical practice
- Dose escalation from adalimumab 40 mg q2w to 40 mg qw was permitted after week 16 in patients who had not achieved at least 20% improvement in TJC and SJC. By week 24, dosing for 8.6% of patients on adalimumab was adjusted
STUDY LIMITATIONS (MONARCH)
- 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 these data.
DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy-Fatigue; q2w=once every 2 weeks; qw=once daily; TJC=tender joint count; SJC=swollen joint count; DMARDs=disease-modifying antirheumatic drugs; MTX=methotrexate.
MONARCH and MONARCH OLE data are not included in the KEVZARA US full Prescribing Information.
MONOTHERAPY
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.1
greater improvement in DAS28-ESR
than adalimumab at week 241
change in das28-esr
at week 241
- *Difference: -1.08 (95% CI: -1.36 to -0.79).
DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; MTX-IR=methotrexate inadequate response; LS=least squares; SE=standard error; q2w=once every 2 weeks.
KEVZARA patients achieved low disease activity (DAS28-ESR <2.6) vs adalimumab monotherapy
(26.6% vs 7.0%; P<0.0001)1
IMPROVED PHYSICAL FUNCTION vs ADALIMUMAB
Significantly greater improvements in HAQ-DI were achieved with KEVZARA monotherapy vs adalimumab monotherapy at 24 weeks.1
MONOTHERAPY
greater improvement in HAQ-DI
vs adalimumab at week 241
Change from baseline in HAQ-DI
at week 241
- HAQ-DI=Health Assessment Questionnaire-Disability Index; MTX-IR=methotrexate inadequate response; LS=least squares; q2w=once every 2 weeks.
PROVIDED GREATER CLINICAL
RESPONSE vs ADALIMUMAB
Significantly more patients achieved ACR responses with KEVZARA monotherapy vs adalimumab monotherapy through week 24.1
ACR Responses at week 241
- *P<0.01.
- ACR20=American College of Rheumatology 20% improvement criteria; MTX-IR=methotrexate inadequate response; q2w=once every 2 weeks.
More patients achieved greated control of disease activity
with KEVZARA vs adalimumab1
Long-Term Monotherapy
Monotherapy
MONARCH OLE STUDY DESIGN: A 276-week (ongoing) randomized, double-blind, double-dummy phase 3 superiority study extension designed to assess the safety and efficacy of long-term continuous KEVZARA monotherapy and switching from adalimumab monotherapy to KEVZARA monotherapy in 320 adult patients who completed the MONARCH study. Primary endpoint was safety. Secondary endpoints included DAS28-ESR, DAS28-CRP, HAQ-DI, CDAI, SDAI, and ACR20/50/70.1
PRIMARY ENDPOINT DATA1
- Overall, safety observations in the OLE population were consistent with those in the MONARCH study and previous studies of KEVZARA, with no unexpected safety signals
- Long-term safety and efficacy of KEVZARA were demonstrated in patients who continued treatment with KEVZARA from MONARCH through OLE ≥72 weeks
DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; DAS28-CRP=disease activity score 28-C-reactive protein; HAQ-DI=Health Assessment Questionnaire-Disability Index; CDAI=Clinical Disease Activity Index; SDAI=Simple Disease Activity Index; ACR20=American College of Rheumatology 20% improvement criteria.
Reference: 1. Burmester GR, Strand V, Rubbert-Roth A, et al. Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. RMD Open. 2019;5(2):e001017. doi:10.1136/rmdopen-2019-001017.
MONARCH OPEN-LABEL EXTENSION (OLE) STUDY LIMITATIONS AND ADDITIONAL STUDY CONTEXT
- These data are not included in the KEVZARA US full Prescribing Information. Data presented are truthful and not misleading
- Long-term safety analysis included all patients who received at least 1 dose of KEVZARA monotherapy
- Analysis of clinical data was based on all available data as observed
- Data presented are descriptive in nature and no statistical comparisons are made
- 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
Given the limitations and context described above, caution should be used in interpreting OLE data. There are limitations associated with open-label study design, including decreasing sample size and potential continued involvement of responders and attrition of non-responders. Data presented are descriptive in nature and no statistical comparisons are made.
Please see Study Context and Limitations above for more information.
MONARCH OPEN-LABEL EXTENSION DATA: INTERPRET WITH CAUTION
CHANGE IN Disease Activity
baseline in DAS28-ESR1-3
- DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; SE=standard error; q2w=once every 2 weeks.
Changes in disease activity were measured in both patients who continued treatment with KEVZARA monotherapy and in those who switched treatment from adalimumab to KEVZARA
MONARCH OPEN-LABEL EXTENSION DATA: INTERPRET WITH CAUTION
IMPROVEMENT IN PHYSICAL FUNCTION
- HAQ-DI=Health Assessment Questionnaire-Disability Index; SE=standard error; q2w=once every 2 weeks.
MONARCH OPEN-LABEL EXTENSION DATA: INTERPRET WITH CAUTION
OBSERVED ACR clinical response
IN OPEN-LABEL EXTENSION (OLE)2
- *ACR response is based on change from original study baseline and not OLE baseline.
ACR20=American College of Rheumatology 20% improvement criteria; q2w=once every 2 weeks.
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
MONARCH SAFETY PROFILE: NO UNEXPECTED SAFETY SIGNALS WITH KEVZARA
Overall, KEVZARA monotherapy long-term safety was studied in 471 patients, with ≈800 patient-years of exposure, and data were consistent with MONARCH studies1
Mean exposure in the long-term safety population was 1.7 years (max 3.5 years)
- 320 patients (87%) were treated for ≥72 weeks
Incidence rate of AEs was generally stable over time, with no indication of increased incidence rate2,3
MONARCH (MTX-IR) and MONARCH long-term safety populations2,3*†
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 adalimumab3
Safety observations in the long-term population were generally consistent with those in the randomized, controlled population.4
- *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; †Patients from the KEVZARA ONE study population were included in these long-term monotherapy safety data; ‡One patient was randomized, but not treated, in the adalimumab group and was not included in the safety population; §Patient years per group are as follows: 80.5 (adalimumab 40 mg), 80.1 (KEVZARA 200 mg), and 348.1 (long-term safety population for KEVZARA 200 mg). ||In 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; ¶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; #Protocol defined as ≥2 doses within 11 calendar days or within 6 days for adalimumab-treated patients who switched to weekly dosing; **Dyslipidemia was defined by standardized MedDRA query.2,3
MTX-IR=methotrexate inadequate response; q2w=once every 2 weeks; PY=patient-years; IR=incidence rate; TEAE=treatment emergent adverse event; ALT=alanine aminotransferase.
References: 1. Fleischmann R, Genovese M, Lin Y, et al. Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years’ follow-up. Rheumatology (Oxford). 2019. doi:10.1093/rheumatology/kez265. [Epub ahead of print]. 2. Data on file, Sanofi/Regeneron. Integrated summary. October 25, 2019. 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. 4. Burmester GR, Strand V, Rubbert-Roth A, et al. Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. RMD Open. 2019;5(2):e001017. doi:10.1136/rmdopen-2019-001017.
References:
- 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.
- Burmester GR, Strand V, Rubbert-Roth A, et al. Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. RMD Open. 2019;5(2):e001017. doi: 10.1136/rmdopen-2019-001017.
- Data on file, Sanofi/Regeneron. Burmester poster SAT0183. June 2018.