KEVZARA EFFICACY

STUDY DESIGNS


PIVOTAL TRIALSCombination Therapy

MOBILITY (MTX-IR) AND TARGET (TNF-IR) STUDY DESIGNS1,2

KEVZARA® (sarilumab) + MTX/DMARD(s) studied in two pivotal trials
KEVZARA® (sarilumab) + MTX/DMARD(s) studied in two pivotal trials
    MOBILITY and TARGET were randomized, double-blind, placebo-controlled, multicenter studies. 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.1,2
  • MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; MTX=methotrexate; RA=rheumatoid arthritis; hsCRP=high-sensitivity C-reactive protein; anti-CCP=anti-cyclic citrullinated peptide; RF=rheumatoid factor; SJC=swollen joint count; TJC=tender joint count; 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; TNFi=tumor necrosis factor inhibitor; DMARDs=disease-modifying antirheumatic drugs.

OPEN-LABEL EXTENSION

Combination Therapy

KEVZARA + MTX/DMARD(s) SAFETY AND EFFICACY EVALUATED OVER TIME3

KEVZARA® (sarilumab) and MTX/DMARD(s) safety and efficacy evaluated over time
KEVZARA® (sarilumab) and 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 Open-Label Extension (OLE)3
  • Long-term safety was evaluated in all 2887 adult patients who received ≥1 dose of KEVZARA in combination with DMARD(s)3

EXTEND 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
  • 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)

LONG-TERM EFFICACY ANALYSIS

  • Efficacy assessments in this analysis did not include all 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.4,5
  • 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.3
  • Patients in the EASY OLE study received KEVZARA 150 mg regardless of their prior treatment.6
  • MTX=methotrexate; DMARDs=disease-modifying antirheumatic drugs; MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; q2w=once every 2 weeks; TNF=tumor necrosis factor.

HEAD-TO-HEAD SUPERIORITY TRIAL

Monotherapy

MONARCH (MTX-IR) STUDY DESIGN7

MONARCH

A randomized, double-blind, double-dummy phase 3 superiority study to evaluate the efficacy and safety of KEVZARA monotherapy vs adalimumab monotherapy7*†

KEVZARA® (sarilumab) studied as monotherapy in a head to head superiority study against adalimumab

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 monotherapy 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.7
  • After week 16, dose escalation to adalimumab qw was permitted for patients who did not achieve ≥20% improvement in TJC and SJC.7
  • 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.8
  • MTX-IR=methotrexate inadequate response; DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; CRP=C-reactive protein; SJC=swollen joint count; TJC=tender joint count; q2w=once every 2 weeks; ACR20=American College of Rheumatology 20% improvement criteria; DAS28-CRP=disease activity score 28-C-reactive protein; HAQ-DI=Health Assessment Questionnaire-Disability Index; FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy-Fatigue; ITT=intent to treat; SC=subcutaneous.

MONARCH OPEN-LABEL EXTENSION

Monotherapy

MONARCH (MTX-IR) OLE STUDY DESIGN7

MONARCH OPEN-LABEL EXTENSION (OLE)

An extension designed to assess the safety and efficacy of long-term continuous KEVZARA monotherapy and switching from adalimumab monotherapy to KEVZARA monotherapy9

KEVZARA® (sarilumab) studied as monotherapy in a head to head superiority study against adalimumab evaluated over time

MONARCH 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 these data.

  • *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.8
  • MTX-IR=methotrexate inadequate response; MTX=methotrexate; DAS28-ESR=Disease Activity Score-28 Erythrocyte Sedimentation Rate; CRP=C-reactive protein; SJC=swollen joint count; TJC=tender joint count; q2w=once every 2 weeks; ACR20=American College of Rheumatology 20% improvement criteria; 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; ITT=intent to treat; SC=subcutaneous; qw=once daily.

References:

  • 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 rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2017;69(2):277-290.
  • 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].
  • 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 September 3, 2020.
  • National Library of Medicine. 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 September 3, 2020.
  • Data on file, Sanofi/Regeneron. Integrated summary. October 25, 2019.
  • 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.
  • 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.