LONG-TERM
COMBINATION THERAPY
References:
Relevant Trials: Long-term Combination Therapy
COMBINATION OPEN-LABEL
EXTENSION (OLE) STUDY DESIGN
KEVZARA + MTX/DMARD(s) SAFETY AND EFFICACY EVALUATED OVER TIME1
INCIDENCE OF ADVERSE EVENTS (PRIMARY ENDPOINT)
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. 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. 3. 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. 4. Data on file, Sanofi/Regeneron. Integrated summary. October 25, 2019.
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.
OPEN-LABEL EXTENSION (OLE) STUDY LIMITATIONS AND ADDITIONAL STUDY CONTEXT
LONG-TERM SAFETY ANALYSIS
LONG-TERM EFFICACY ANALYSIS
DMARDs=disease-modifying antirheumatic drugs.
Given the limitations and context described above, caution should be used in interpreting open-label extension (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.
Data in patients who received initial treatment with KEVZARA compared with those who initially received placebo.
This analysis has not been performed for the TNF-IR population.
HAQ-DI was measured in patients who
continued treatment with KEVZARA for up to 5 years1,2
Inhibition of structural progression was measured in patients who
continued treatment with KEVZARA for up to 5 years2
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.
Studied in ≈3000 MTX-IR and TNF-IR patients with over 8100 patient-years of exposure1-3
Mean duration of treatment in the safety population (N=2887) was 2.8 years (max 7.3 years), representing 8188 cumulative PY of exposure
Incidence rate of AEs was generally stable over time, with no indication of increased incidence rate in serious AEs and serious infections.2,3
In the long-term safety population, the rate of thromboembolic events (MedDRA high-level group term “embolism and thrombosis”) were 0.8 per 100 PY (as reported and evaluated post hoc; not a prespecified AESI)2
Safety observations in the open-label extension population were consistent with those in the placebo-controlled trials.2,3
MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; PY=patient-years; IR=incidence rate; MTX=methotrexate; DMARDs=disease-modifying antirheumatic drugs; q2w=every 2 weeks; TEAE=treatment-emergent adverse event; ALT=alanine aminotransferase; AESI=adverse event of special interest; DVT=deep vein thrombosis; PE=pulmonary embolism.
References: 1. KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc. 2. 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]. 3. Data on file, Sanofi/Regeneron. Integrated summary. October 25, 2019.