Head-to-Head
Monotherapy and OLE
RELEVANT TRIALS: MONARCH, MONARCH OPEN-LABEL EXTENSION
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
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
USE OF ADALIMUMAB
STUDY LIMITATIONS (MONARCH)
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.
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
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
Significantly greater improvements in HAQ-DI were achieved with KEVZARA monotherapy vs adalimumab monotherapy at 24 weeks.1
greater improvement in HAQ-DI
vs adalimumab at week 241
Significantly more patients achieved ACR responses with KEVZARA monotherapy vs adalimumab monotherapy through week 24.1
More patients achieved greated control of disease activity
with KEVZARA vs adalimumab1
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
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
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.
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
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
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)
Incidence rate of AEs was generally stable over time, with no indication of increased incidence rate2,3
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
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.
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