KEVZARA EFFICACY
SIGNS AND SYMPTOMS
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)
CONTROL OF IL-6–RELATED SIGNS AND SYMPTOMS
RELEVANT TRIALS: MOBILITY, TARGET, MONARCH
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; TJC=tender joint count; SJC=swollen joint count; SC=subcutaneous; qw=once daily.
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 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.
- 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 data are not included in the KEVZARA US full Prescribing Information. Please see Study Context and Limitations for details.
RAPIDLY NORMALIZED CRP LEVELS1,2
CRP levels returned to normal (<10 mg/L) as early as 2 weeks after the first dose of KEVZARA.3,4*
- *CRP levels were not a prespecified endpoint. Studied as part of the ACR20/50/70 response endpoints in MOBILITY, TARGET, MONARCH.3,5
- CRP=C-reactive protein; MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; LS=least squares; MTX=methotrexate; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs; ACR20=American College of Rheumatology 20% improvement criteria.
REDUCTIONS IN MORNING STIFFNESS5,6
- Morning stiffness was not assessed in MOBILITY.
- TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; MTX-IR=methotrexate inadequate response; LS=least squares; VAS=visual analogue scale; DMARDs=disease-modifying antirheumatic drugs; q2w=once every 2 weeks.
REDUCTIONS IN PAIN2,5,7
- MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; LS=least squares; VAS=visual analogue scale; MTX=methotrexate; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.
Common adverse reactions in pre-rescue, placebo-controlled trials1*
- *Adverse reactions occurring in ≥2% of patients administered KEVZARA 200 mg or KEVZARA 150 mg + DMARD(s) and greater than observed in patients on placebo + DMARD(s).
- Medically relevant AE occurring at an incidence of less than 2% in patients with RA treated with KEVZARA in controlled studies was oral herpes1
- Decrease in ANC was not associated with higher incidence of infections, including serious infections1
- In the long-term safety population, the overall rates of serious infections, GI perforations, neutrophil counts, platelet counts, and lipid parameters were consistent with what was observed in the placebo-controlled trials1
DMARDs=disease-modifying antirheumatic drugs; ALT=alanine aminotransferase; ANC=absolute neutrophil count; GI=gastrointestinal.
Reference: 1. KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc.
KEVZARA SAFETY PROFILE AS MONOTHERAPY1,2
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
- *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) and 80.1 (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
- q2w=once every 2 weeks; PY=patient-years; 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.
References:
- 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.
- KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc.
- 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. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/review-criteria-assessment-c-reactive-protein-crp-high-sensitivity-c-reactive-protein-hscrp-and-0. Accessed September 3, 2020.
- 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):e000416. 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.
- Strand V, Kosinski M, Chen CI, et al. Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial. Arthritis Res Ther. 2016;18:198. doi:10.1186/s13075-016-1096-9.