Employee Of Sanofi Research Articles

1157. Immune Persistence and Booster Response of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) 5 Years After Primary Vaccination of Adults ≥59 Years of Age

Abstract Background MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It is approved for use in persons aged ≥2 years in the US and persons aged ≥1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. The second stage of a 2-stage study of MenACYW-TT, reported herein, evaluated immune persistence among older adults who received primary vaccination with either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT five years earlier at age ≥ 56 years. The immunogenicity and safety of a MenACYW-TT booster dose given to this population were also evaluated. Methods This was a Phase 3, 2-stage, randomized, open-label, multi-center study (NCT04142242) of adults aged ≥59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune persistence and response were assessed with a serum bactericidal assay using human complement (hSBA). Safety data were collected for up to 30 days after booster vaccination. All analyses were descriptive. Results Of the initial study population (N=471), 70 adults participated in Stage II of the study. At 5 years post-primary vaccination, seroprotection (hSBA ≥ 1:8) rates (SPRs) and hSBA geometric mean titers (GMTs) declined in both MenACYW-TT- and MPSV4-primed subjects, with SPRs and hSBA GMTs for serogroups A, C, W, and Y trending higher in MenACYW-TT- vs MPSV4-primed subjects (Table 1). Thirty days after booster vaccination, hSBA GMTs and SPRs increased from pre-booster for all serogroups and were, along with seroresponse rates, higher in MenACYW-TT-primed subjects compared to MPSV4-primed subjects (Table 2). Rates of AEs following booster vaccination were similar regardless of priming vaccine. No safety concerns were identified. Conclusion Five years after primary vaccination, immune persistence tended to be greater for MenACYW-TT vs MPSV4. A MenACYW-TT booster was well tolerated and immunogenic in adults ≥ 61 years, when administered 5 years after primary vaccination with either MPSV4 or MenACYW-TT. Disclosures Corwin A. Robertson, MD, MPH, FACP, Sanofi: Sanofi employee|Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Katherine Galarza, MD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Alexandre Selmani, PhD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Philipp Oster, MD, Sanofi: Sanofi employee

1743. Health Care Resource Utilisation (HCRU) Due to Respiratory Syncytial Virus (RSV) Before the Age of Two in England

Abstract Background RSV is responsible for 33 million lower respiratory tract infections (LRTI) worldwide. The highest burden occurs in infants < 1 year of age during RSV season, which is from October to February in England. Due to lack of routine laboratory testing, its true disease burden is unknown. This study aimed to estimate the respiratory related primary and secondary care healthcare resource utilisation (HCRU) of RSV admissions before the age two in England. Methods This retrospective cohort study used Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked data to establish a birth cohort of all infants born between 01/03/2015 and 28/02/2017 (n=449,591). Case cohorts included infants under two with a hospital admission of: 1) confirmed RSV (n=4,813), 2) bronchiolitis (n=22,913), 3) any RTI (n=56,871). Each case cohort was compared with all birth cohort infants without the corresponding admission (comparative cohorts). Respiratory related HCRU (primary care, outpatient, accident and emergency [A&E], and inpatient admissions) were estimated in the month prior to and up to 24 months following the first admission in each cohort. Results The RSV-coded cohort had the highest HCRU overall, mean (SD) of 5.1 (4.8) admissions vs. 1.5 (2.4) in its comparative cohort (71% difference). This difference was largely due to A&E and inpatient admissions. Comparable results were found for bronchiolitis-coded and RTI-coded cohorts. The highest rates of inpatient admissions were observed for the RSV-coded case cohort, and these occurred during the calendar months of November and December. Inpatient admissions were largely among infants up to 12 months of age and included infants that were born both before and during the season (Figure 1). Conclusion Infants with an RSV admission had higher HCRU than infants without. Most hospitalisations occurred in November and December when services are at their most stretched. During the first year of life, the HCRU rates observed for infants born before and in the season were equally very high, emphasizing the need for preventative strategies to all infants entering their first RSV season. Funding: This research was funded by collaborative agreement with Sanofi / AstraZeneca and is part of the RODEO research program for RSV disease. Disclosures Maria João Fonseca, n/a, Sanofi: Advisor/Consultant Mathieu Bangert, PhD, Sanofi: Staff member Rolf Kramer, n/a, Sanofi: Stocks/Bonds Richard Hudson, n/a, Sanofi: I am an employee of Sanofi|Sanofi: Stocks/Bonds

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism.

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism.

Evaluating the Effect of a Bruton’s Tyrosine Kinase Inhibitor in a Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis (P2-3.012)

<h3>Objective:</h3> To characterize a central nervous system (CNS)-penetrant, tolebrutinib-like Bruton’s tyrosine kinase inhibitor (BTKi) in murine experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) for its potential to modulate disease progression and expression of genes linked to disease-associated microglia (DAM). <h3>Background:</h3> BTK inhibition may slow disease progression in people with MS by targeting microglia-driven neuroinflammation in the CNS. We previously showed that a structural analogue of the BTKi tolebrutinib can reduce BTK-dependent inflammatory signalling in microglia in the mouse brain, using the cuprizone-mediated model of demyelination. <h3>Design/Methods:</h3> Female C57BL/6 mice were immunized with MOG_35–55 peptide (250 μg/mouse; two subcutaneous injections in the lower back) to induce EAE. Animals were randomized to receive vehicle (n=15) or oral BTKi (15 mg/kg; n=15), starting at clinical score of 1.0–1.5. Treatment groups were blinded until after final data analysis. Cohorts were monitored daily for development and severity of disease symptoms. After 10 days of treatment, spinal cord and plasma samples were taken for transcriptome analysis and neurofilament heavy chain (NfH) concentration measurement, respectively. <h3>Results:</h3> BTK inhibition significantly reduced the clinical score in the EAE mice, with significant differences between treatment groups starting after two days of treatment and continuing until end of study (Day 10). BTK inhibition significantly reduced plasma Nfh concentrations. A BTK-dependent transcriptional signature was identified, with BTK inhibition found to modulate pathways relevant to MS pathology. BTK inhibition modulated mRNA expression of genes that had previously been linked to DAM and/or are associated with BTK-signalling. <h3>Conclusions:</h3> We extended our previous <i>in vivo</i> findings from a demyelination model by demonstrating that dosing with a BTKi halted disease progression in an immune-mediated model of MS. This therapeutic benefit was accompanied by modulated expression of genes associated with activated microglia, which could abrogate microglia-driven neuroinflammation implicated in disease progression in MS. <b>Disclosure:</b> Dr. Gruber has received personal compensation for serving as an employee of Sanofi. Dr. Gruber has received stock or an ownership interest from Sanofi. Dr. Blazier has received personal compensation for serving as an employee of Sanofi. Lan Lee has nothing to disclose. Dr. Ryan has nothing to disclose. Dr. Cheong has received personal compensation for serving as an employee of Sanofi. Ms. Havari has received personal compensation for serving as an employee of sanofi. Timothy J. Turner has received personal compensation for serving as an employee of Sanofi. Timothy J. Turner has received stock or an ownership interest from Sanofi. Timothy J. Turner has received intellectual property interests from a discovery or technology relating to health care. Dimitry Ofengeim has received personal compensation for serving as an employee of Sanofi. Dimitry Ofengeim has received stock or an ownership interest from Sanofi. Dimitry Ofengeim has received personal compensation in the range of $500-$4,999 for serving as a Study Section Reveiwer with NIH.

First-in-Human Study of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SAR443820, a Central Nervous System Penetrant RIPK1 Inhibitor in Healthy Participants (S46.005)

<h3>Objective:</h3> To assess safety, tolerability, pharmacokinetics, and pharmacodynamics of SAR443820 in first-in-human, Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose (SAD; Part-1a) and multiple-ascending dose (MAD; Part-2) studies in healthy participants. Part-1b was a separate open-label single-dose study for assessing SAR443820 levels in cerebrospinal fluid (CSF). <h3>Background:</h3> Receptor-interacting serine/threonine protein kinase-1 (RIPK1), which regulates inflammatory signaling and necroptotic cell death, is implicated in several neurodegenerative diseases. SAR443820, a central nervous system (CNS) penetrant oral RIPK1 inhibitor, is being developed in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). <h3>Design/Methods:</h3> In Part-1a, 4 cohorts (n=8 each; 6 SAR443820, 2 placebo) received single-ascending doses of SAR443820 (up to 4-fold the lowest dose) or placebo. Part-1b included 2 single-dose cohorts (n=6 each) receiving the lowest and 4-fold the lowest doses of SAR443820. In Part-2, 4 cohorts (n=10 each; 8 SAR443820, 2 placebo) received 14-day SAR443820 or placebo in multiple-ascending doses. <h3>Results:</h3> Overall, SAR443820 was well-tolerated with no treatment-related serious adverse events (AEs) or permanent treatment discontinuation. Most common AEs were dizziness and headache. No clinically meaningful changes were noted in hematology, chemistry, vital signs, or electrocardiogram parameters. There were no major deviations from dose proportionality for maximum concentration (C_max) and area under the curve (AUC) over the range of SAR443820 doses. Mean plasma half-lives ranged between 6–8h and 7–9h in SAD and MAD cohorts, respectively. Mean CSF-to-unbound plasma concentration ratio suggested high CNS-penetrance. Concentration-QTcF analyses did not indicate any potential for SAR443820 to cause relevant change in QTcF. Maximum median inhibition of phosphorylated-Ser166-RIPK1 levels across all SAR443820 groups reflected a marked target engagement. <h3>Conclusions:</h3> The first-in-human study demonstrated that single and repeated SAR443820 doses were generally safe and well-tolerated, with favorable pharmacokinetics, high CNS-penetrance, and robust RIPK1-target engagement, supporting further development in actively recruiting Phase 2 trials in ALS (Himalaya; NCT05237284) and MS (K2; ACT16753). <b>Disclosure:</b> Mrs. HINCELIN-MERY has nothing to disclose. Pascale Lewanczyk has nothing to disclose. Mrs. Cantalloube has received personal compensation for serving as an employee of Sanofi. Mr. Nicolas has nothing to disclose. Myriam Benamor has nothing to disclose. Dr. Pomponio has received personal compensation for serving as an employee of Sanofi. Dr. Pomponio has stock in sanofi. Dr. KRUPKA has nothing to disclose. Dimitry Ofengeim has received personal compensation for serving as an employee of Sanofi. Dimitry Ofengeim has received stock or an ownership interest from Sanofi. Dimitry Ofengeim has received personal compensation in the range of $500-$4,999 for serving as a Study Section Reveiwer with NIH. Dr. Eastenson has nothing to disclose. Dr. Xiong has received personal compensation for serving as an employee of Sanofi. Dr. Atassi has received personal compensation for serving as an employee of Sanofi. Dr. Atassi has stock in Sanofi.

Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Participants With Relapsing Multiple Sclerosis: 2.5-Year Results (S16.010)

Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Participants With Relapsing Multiple Sclerosis: 2.5-Year Results (S16.010)

Exploring New Imaging Biomarkers: 3D Conformational Analysis Of The Medulla And Upper Cervical Spinal Cord In People With Relapsing Multiple Sclerosis (P11-3.015)

<h3>Objective:</h3> Explore three-dimensional (3D) medulla-upper cervical spinal cord (MUCSC) conformational imaging metrics as biomarkers in multiple sclerosis (MS). <h3>Background:</h3> Measures of spinal cord atrophy are associated with MS disease progression but have yet to emerge as reliable biomarkers of treatment efficacy. 3D MUCSC conformational analysis is a new technique that may provide additional information about neurodegenerative changes in MS beyond conventional magnetic resonance imaging metrics. In the placebo-controlled Phase 3 TEMSO trial (NCT00134563), teriflunomide 14 mg/day lowered the risk of disability worsening and reduced brain volume loss in participants with relapsing MS. 3D MUCSC conformational analysis of the TEMSO dataset has not been explored. <h3>Design/Methods:</h3> TEMSO baseline and 2-year end of study follow-up 3D T1-Magnetization Prepared Rapid Gradient Echo (MP-RAGE) images acquired primarily at 1.5T were assessed for quality, then segmented and analyzed using in-house proprietary software. Change from baseline in MUCSC volume, local curvature and surface texture were summarized with descriptive statistics. <h3>Results:</h3> Quality assessments led to the exclusion of 481 of the 799 TEMSO participants, comprising 64.0%, 62.1%, and 54.5% of participants in the placebo, 7 mg/day, and 14 mg/day arms, respectively. Mean age and disease duration were lower for placebo participants versus teriflunomide arms. No between-group differences were apparent for mean (SD) change from baseline in MUCSC volume (−86±236, −85±218, and −75±218 mm³ for placebo, 7 mg/day, and 14 mg/day arms, respectively), mean curvature (0.01±0.06, 0.02±0.07, and 0.02±0.07 mm), or surface texture (−15.6±28.0, −21.3±26.6, and −19.0±24.2 triangle count). <h3>Conclusions:</h3> 3D conformational analysis of MP-RAGE images from the TEMSO trial showed no discernable between-group differences for MUCSC surface features or volume; however, imbalanced exclusion of participants during quality assessment likely introduced attrition bias. Further development of 3D conformational metrics as MS biomarkers may better illuminate mechanisms related to neurodegenerative changes and treatment efficacy. <b>Disclosure:</b> Miss Moog has nothing to disclose. Janneke Van Wingerden has received personal compensation for serving as an employee of Sanofi Genzyme. Dr. Sanofi has received personal compensation for serving as an employee of Sanofi. Dr. Sanofi has received personal compensation for serving as an employee of Sanofi. Dr. Sanofi has stock in Sanofi. Dr. Sanofi has stock in Sanofi. Dr. Geertsen has received personal compensation for serving as an employee of Sanofi. Dr. Rawlings has received personal compensation for serving as an employee of Sanofi. Dr. Rawlings has stock in Sanofi. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Okuda has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Celgene. Dr. Okuda has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for VielaBio.

MRI Outcomes from the Long-term Extension Study of Tolebrutinib in Patients with Relapsing Multiple Sclerosis: 2-Year Results (P6-3.012)

MRI Outcomes from the Long-term Extension Study of Tolebrutinib in Patients with Relapsing Multiple Sclerosis: 2-Year Results (P6-3.012)

Lack of Rebound Disease Activity in Participants with Relapsing Multiple Sclerosis Following Placebo Run-out in the Tolebrutinib Phase 2b Trial (P6-3.006)

Lack of Rebound Disease Activity in Participants with Relapsing Multiple Sclerosis Following Placebo Run-out in the Tolebrutinib Phase 2b Trial (P6-3.006)

Exploring the Utility of ActiGraph in Measuring Gait Impairment and Physical Activity in Patients with MS Using Digital Biomarkers (P3-3.013)

<h3>Objective:</h3> To report findings from a pilot sub-study of the Phase 2b tolebrutinib long-term safety (LTS) study (NCT03889639) that assessed compliance with a wearable ActiGraph device and to describe the Phase 3 validation sub-study design assessing the use of actigraphy in measuring gait changes in participants with progressive multiple sclerosis (PwPMS). <h3>Background:</h3> Gait impairment is a common, clinically relevant issue for MS patients. Traditional disability assessments by Expanded Disability Status Scale [EDSS], Timed 25-Foot Walk are widely used, but more sensitive, objective, and clinically meaningful gait impairment measures are needed. <h3>Design/Methods:</h3> The LTS pilot sub-study assessed compliance with the ActiGraph device (defined as 8/14 compliant days with ≥11h/day of device wear/monitoring period) that monitored gait and activity over 4 one-month monitoring periods. The Phase 3 validation sub-study will recruit ~250 PwPMS from PERSEUS (NCT04458051) and HERCULES (NCT04411641) tolebrutinib trials. Participants will be monitored 14 days/month for ≥12 months. Primary endpoint is correlation of gait measures with standard disability progression assessments. Key gait measures include gait speed, step duration, and step length. Physical activity measures include number of steps and walking episodes. Secondary endpoints are to establish normative values for velocity, stride length, and step duration for subsets of EDSS. <h3>Results:</h3> Compliance in the Actigraphy LTS pilot sub-study was 61%–90% over 4 monitoring periods, with a mean daily wear time ranging from 5.9–14.9h. 79% of participants had a mean daily wear time of &gt;10h. Per literature reports, actigraphy gait measures were correlated with EDSS. Findings from Actigraphy LTS pilot sub-study supported the design of the Phase 3 validation sub-study. <h3>Conclusions:</h3> Actigraphy LTS pilot sub-study showed that participants can use the ActiGraph device with relatively good compliance. This Phase 3 validation sub-study will provide further clinical data on actigraphy as a more sensitive measure to track disability progression in PwPMS. <b>Disclosure:</b> Dr. Abou Zeid has nothing to disclose. Xiaoyu Jiang has received personal compensation for serving as an employee of Sanofi. Dr. Orogun has nothing to disclose. Dr. Sarker has received personal compensation for serving as an employee of Sanofi. Dr. Syed has received personal compensation for serving as an employee of Sanofi US.

MRI, Efficacy, and Safety of Tolebrutinib in Patients with Highly Active Disease (HAD): 2-Year Data from the Phase 2b Long-term Safety (LTS) Study (P6-3.017)

MRI, Efficacy, and Safety of Tolebrutinib in Patients with Highly Active Disease (HAD): 2-Year Data from the Phase 2b Long-term Safety (LTS) Study (P6-3.017)

Comparative CNS Pharmacology of Tolebrutinib Versus Other BTK Inhibitor Candidates for Treating MS (S46.007)

<h3>Objective:</h3> Compare three BTK inhibitors in Phase 3 development in multiple sclerosis (MS) according to relative potencies and CNS exposure. <h3>Background:</h3> Modulating CNS neuroinflammation represents a paradigm shift for treating MS. Tolebrutinib is a covalent BTK inhibitor designed and selected to optimize both potency and exposure to modulate BTK signaling within the CNS. <h3>Design/Methods:</h3> We used in vitro kinase assays, cellular activation assays, and pharmacokinetic (PK) sampling of cerebrospinal fluid (CSF) in the non-human primate (NHP) cynomolgus to compare tolebrutinib, evobrutinib, fenebrutinib under identical conditions. We then evaluated the CSF PK of tolebrutinib in healthy volunteers. <h3>Results:</h3> Kinase assays demonstrated that tolebrutinib reacted with BTK 65-times faster than evobrutinib (K_inact/K_i = 4.37 × 10⁻³ and 6.82 × 10⁻⁵ nM⁻¹*s⁻¹, respectively). Fenebrutinib, a reversible antagonist had a K_i value of 4.7 nM. Because of the slow off-rate (1.54 × 10⁻⁵ s⁻¹), the forward rate was also very slow (3.28 × 10³ M⁻¹ * s⁻¹). Estimated cellular potency (using B cell activation) was consistent with kinase data (IC50 = 0.7 nM, 34.5 nM, and 2.9 nM, respectively). In NHP, we observed similar levels of exposure in the CSF after oral doses of 10 mg/kg for each candidate. However, tolebrutinib CSF exposure (4.8 ng/mL) (kp, uu CSF=0.40) exceeded the IC90, while evobrutinib (3.2 ng/mL) (kp, uu CSF=0.13) and fenebrutinib (12.9 ng/mL) (kp, uu CSF=0.15) failed to reach the IC50. In healthy volunteers, a single oral dose of 60 or 120 mg resulted in bioactive CSF levels between 2 and 4 hrs. (0.51 and 1.03 ng/mL, respectively). <h3>Conclusions:</h3> Next-generation drug candidates in MS must achieve pharmacologically-relevant concentrations in the CNS to address the existing treatment gap. In these NHP experiments, tolebrutinib was the only BTK inhibitor to show bioactive CSF levels, adding to the evidence that tolebrutinib has potential to slow disability accumulation via modulating neuroinflammation. <b>Disclosure:</b> Timothy J. Turner has received personal compensation for serving as an employee of Sanofi. Timothy J. Turner has received stock or an ownership interest from Sanofi. Timothy J. Turner has received intellectual property interests from a discovery or technology relating to health care. Dr. NICOLAS has nothing to disclose. Mrs. Brun has nothing to disclose. Dimitry Ofengeim has received personal compensation for serving as an employee of Sanofi. Dimitry Ofengeim has received stock or an ownership interest from Sanofi. Dimitry Ofengeim has received personal compensation in the range of $500-$4,999 for serving as a Study Section Reveiwer with NIH.

Patterns and Predictors of Multiple Sclerosis Phenotype Transitions: A Longitudinal Analysis Using the CLIMB Study (P5-3.018)

Patterns and Predictors of Multiple Sclerosis Phenotype Transitions: A Longitudinal Analysis Using the CLIMB Study (P5-3.018)

Effect of RIPK1 Inhibitor, SAR443820, on Serum Neurofilament Light Levels in Patients with Multiple Sclerosis: A Phase 2 Trial Design (P6-3.011)

Effect of RIPK1 Inhibitor, SAR443820, on Serum Neurofilament Light Levels in Patients with Multiple Sclerosis: A Phase 2 Trial Design (P6-3.011)

Comparison of 2-year Teriflunomide Outcomes between DMT-naive and switch patients with Relapsing MS: subanalysis of the Real-World TERICARE study (P6-3.003)

<h3>Objective:</h3> To evaluate the effect of teriflunomide on clinical and patient-reported outcomes (PROs) in disease-modifying therapy (DMT)-naive and previously treated (switch) patients with relapsing-remitting multiple sclerosis (RRMS). <h3>Background:</h3> Clinical trials and real-world evidence have shown that patients with RRMS benefit from teriflunomide regardless of prior exposure to DMT. <h3>Design/Methods:</h3> TERICARE was a multicentre, observational and prospective study in Spain. RRMS patients with no relapses within the last 30 days before the inclusion received teriflunomide for 2-years. This analysis compared the annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), disability worsening, quality of life (Multiple Sclerosis Impact Scale, MSIS-29), fatigue (Modified Fatigue Impact Scale-5), and depression (Beck Depression Inventory-II) between DMT-naive and switch patients. <h3>Results:</h3> Of 325 patients included, 117 were DMT-naive and 208 switch patients. At baseline, DMT-naive was younger than switch patients (40.9 <i>vs</i> 44.4 years; p=0.003), had shorter disease duration (3.1 <i>vs</i> 9.5 years; p&lt;0.001), lower EDSS score (1.3 <i>vs</i> 2.0; p&lt;0.001), higher number of relapses in the last 2 years (1.3 <i>vs</i> 0.6; p&lt;0.001) and ARR (95% CI) (0.63 [0.53–0.74] <i>vs</i> 0.31 [0.26–0.37]; p&lt;0.001). The ARR was significantly reduced in both groups after 12 months (DMT-naive=0.24; p&lt;0.001; switch=0.21; p=0.032) and 24 months (DMT-naive=0.19; switch=0.16; p&lt;0.001, both groups). A greater reduction of ARR was observed in DMT-naive both at 12 (63% <i>vs</i> 33%) and 24 months (70% <i>vs</i> 49%). Mean change in EDSS score did not vary between groups, nor the percentage of patients with disability worsening at 12 (20% <i>vs</i> 13.2%; p=0.167) and 24 months (24.2% <i>vs</i> 17.6%; p=0.246). DMT-naive experienced a greater and significant reduction (improvement) in psychological MSIS-29 score at month 24 compared to switch group (−7.11 <i>vs</i> −1.48; p=0.019). <h3>Conclusions:</h3> Teriflunomide shows effectiveness in both DMT-naive and switch RRMS patients with a trend towards better relapse and quality of life outcomes in DMT-naive. <b>Disclosure:</b> Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol-Myers-Squibb. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Meca Lallana has received research support from Merck. The institution of Dr. Meca Lallana has received research support from Novartis. The institution of Dr. Meca Lallana has received research support from Roche. The institution of Dr. Meca Lallana has received research support from Sanofi. The institution of Dr. Meca Lallana has received research support from Biogen. Dr. Prieto has nothing to disclose. Dr. Caminero Rodriguez has nothing to disclose. Javier Olaskoaga has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sanofi-Genzyme. Rosa Casademont Portell has received personal compensation for serving as an employee of Sanofi. Mrs. Forner has received personal compensation for serving as an employee of Sanofi.

Improvements in Quality of Life of Patients with Multiple Sclerosis receiving Alemtuzumab in Clinical Practice: LEMVIDA study (P7-3.018)

Improvements in Quality of Life of Patients with Multiple Sclerosis receiving Alemtuzumab in Clinical Practice: LEMVIDA study (P7-3.018)

Baseline Characteristics and Interim Safety in RESPOND: A Phase 4 Study in Children with Spinal Muscular Atrophy (SMA) Treated With Nusinersen After Onasemnogene Abeparvovec (P7-9.003)

Baseline Characteristics and Interim Safety in RESPOND: A Phase 4 Study in Children with Spinal Muscular Atrophy (SMA) Treated With Nusinersen After Onasemnogene Abeparvovec (P7-9.003)

Significant reduction in migraine days with Remote Electrical Neuromodulation (REN) for migraine prevention: A double-blind randomized sham-controlled clinical trial (S47.010)

Significant reduction in migraine days with Remote Electrical Neuromodulation (REN) for migraine prevention: A double-blind randomized sham-controlled clinical trial (S47.010)

Cost-effectiveness analysis of cemiplimab vs pembrolizumab for treatment of advanced cutaneous squamous cell carcinoma.

BACKGROUND: Most cutaneous squamous cell carcinomas (CSCCs) can be treated with surgical excision or radiation; however, approximately 1% of patients develop advanced disease. In 2018, the FDA approved cemiplimab-rwlc as the first programmed cell death-1 (PD-1) monoclonal antibody for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In June 2020, pembrolizumab, another PD-1 monoclonal antibody, was approved for the treatment of patients with recurrent or metastatic CSCC who are not candidates for curative surgery or radiation. We previously reported on the cost-effectiveness of cemiplimab vs historical standard of care for the treatment of advanced CSCC from a US perspective. OBJECTIVE: To estimate the cost-effectiveness of cemiplimab vs pembrolizumab for patients with advanced CSCC in the United States. METHODS: A "partitioned survival" framework was used to assess the cost-effectiveness of cemiplimab vs pembrolizumab. Clinical inputs were based on the most recent data cut of the phase 2 trials for cemiplimab (EMPOWER-CSCC-1; NCT02760498) and pembrolizumab (KEYNOTE-629). Progression-free survival and overall survival were extrapolated using parametric models until all patients had progressed or died. Health state utilities were derived from data collected in the EMPOWER-CSCC-1 trial. Costs included drug acquisition, drug administration, disease management, terminal care, and adverse events and were based on published 2020 US list prices. To assess model uncertainty, 1-way sensitivity and probabilistic sensitivity analyses (PSA) were conducted, alongside scenario analyses evaluating key modeling assumptions. RESULTS: In the base case, cemiplimab resulted in an incremental gain of 3.44 life-years (discounted) and incremental cost-effectiveness ratio (ICER) of $130,329 per quality-adjusted life-year (QALY) vs pembrolizumab. At a willingness-to-pay threshold of $150,000/QALY, PSA indicated a 71% probability that cemiplimab is cost-effective when compared with pembrolizumab. Scenario analysis resulted in ICERs ranging from $115,909 to $187,374. CONCLUSIONS: Findings suggest that cemiplimab is a cost-effective treatment for patients with advanced CSCC, compared with pembrolizumab. These results should be interpreted cautiously in the absence of head-to-head trials; however, in the absence of such data, these results can be used to inform health care decisions over resource allocation. DISCLOSURES: This study was supported by Regeneron Pharmaceuticals, Inc., and Sanofi. Paul, Cope, Keeping, Mojebi, and Ayers are employees of PRECISIONheor, which received funding to produce this work. Chen, Kuznik, and Xu are employees and stockholders of Regeneron Pharmaceuticals, Inc. Sasane is an employee and stockholder of Sanofi, Inc. Konidaris, Atsou, and Guyot are employees of Sanofi, Inc. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication.

POS1169 IMPACT OF THE COVID-19 PANDEMIC ON MORBIDITY AND MORTALITY AMONG SWEDISH PATIENTS WITH INFLAMMATORY JOINT DISEASES VERSUS THE GENERAL POPULATION

Background:Studies from COVID-19 case-repositories among patients with rheumatic diseases have assessed associations (relative risks) between characteristics of the disease and adverse COVID-19 outcomes. Such designs are susceptible to bias from selection of cases reported. Few studies have assessed absolute and relative risks for COVID-19 outcomes in population-based cohorts of patients with inflammatory joint diseases, nor compared these risks to those in the general population.Objectives:To estimate all-cause mortality, absolute and relative risks for severe COVID-19 in patients with chronic inflammatory joint diseases, compared over time and to the general population.Methods:We updated a multi-register nationwide linkage (“ARTIS”) on adults with RA, PsA, AS, SpA or JIA and population referents (matched on sex, age, and region), with data on hospitalizations, admission to intensive care (ICU), and deaths due to COVID-19. We calculated all-cause mortality March-September 2015-2020, and absolute and relative risks for COVID-19 outcomes March-September 2020. Patients were compared to population referents using hazard ratios (HR) from Cox models adjusted for comorbidities and socio-economy.Results:We identified 110567 individuals with inflammatory joint disease (53455 with RA) in Sweden on March 1st 2020, and 484277 matched general population subjects. In all cohorts, the absolute risk of death from any cause in 2020 was higher than 2015-2019 (Figure 1), with a peak in mid-April, but the relative risks of death (vs. the general population) 2020 remained similar to HRs for 2015-2019 (HR for 2020 in Table 1).Among all individuals with inflammatory joint disease in 2020, the risk for hospitalization, admission to ICU, and death due to COVID-19 was 0.5%, 0.04% and 0.1%, respectively (Table 1). HRs (vs. the general population) were elevated for almost all outcomes. HRs for COVID-19 related outcomes (Table 1) were higher than for non-COVID-19 outcomes; adjustment for co-morbidities and socio-economy explained much of these increases, somewhat less so for the former.Figure 1.All-cause mortality in Swedish individuals with inflammatory joint disease and general population, March-September 2020 and the average 2015-2019Table 1.Absolute and relative risks for COVID-19 outcomes in Swedish individuals with inflammatory joint disease compared to general population comparators March-September 2020OutcomeEvents(risk, %)Events (risk, %), general populationHR1*HR2**AllHospitalization, all causes8971 (8.1%)24273 (5.0%)1.65(1.61, 1.69)1.18 (1.15, 1.21)Hospitalization, COVID-19581 (0.5%)1443 (0.3%)1.77 (1.61, 1.95)1.32 (1.19, 1.46)ICU, COVID-1945 (0.04%)162 (0.03%)1.22 (0.88, 1.70)1.17 (0.82, 1.66)Death, all causes1310 (1.2%)3036 (0.6%)1.90 (1.78, 2.02)1.13 (1.05, 1.21)Death, COVID-19161 (0.1%)338 (0.07%)2.09 (1.73, 2.52)1.18 (0.97, 1.44)RAHospitalization, all causes5275 (9.9%)13072 (5.9%)1.71 (1.66, 1.77)1.21 (1.17, 1.25)Hospitalization, COVID-19379 (0.7%)784 (0.4%)2.02 (1.78, 2.28)1.40 (1.23, 1.60)ICU, COVID-1931 (0.06%)79 (0.04%)1.63 (1.08, 2.48)1.53 (0.98, 2.40)Death, all causes968 (1.8%)2026 (0.9%)1.99 (1.85, 2.15)1.18 (1.09, 1.28)Death, COVID-19134 (0.3%)245 (0.11%)2.28 (1.85, 2.81)1.27 (1.02, 1.59)PsA AS SpA JIAHospitalization, all causes3696 (6.5%)11201 (4.3%)1.54 (1.48, 1.59)1.16 (1.11, 1.20)Hospitalization, COVID-19202 (0.4%)659 (0.3%)1.41 (1.20, 1.65)1.20 (1.02, 1.41)ICU, COVID-1914 (0.02%)83 (0.03%)0.78 (0.44, 1.37)0.76 (0.43, 1.37)Death, all causes342 (0.6%)1010 (0.4%)1.56 (1.38, 1.76)0.98 (0.86, 1.12)Death, COVID-1927 (0.05%)93 (0.04%)1.34 (0.87, 2.05)0.83 (0.54, 1.28)*HR1 unadjusted, matched (age, sex, and region)**HR2, as HR1 but adjusted for comorbidities and socio-economyConclusion:Risks of severe COVID-19 were increased among patients with inflammatory joint diseases, but similar increases were seen for non-COVID-19 morbidity. Co-morbidities and socio-economy explain much of this increase.Disclosure of Interests:Hannah Bower: None declared, Thomas Frisell: None declared, Daniela Di Giuseppe: None declared, Bénédicte Delcoigne: None declared, Gerd-Marie Alenius: None declared, Eva Baecklund: None declared, Katerina Chatzidionysiou Speakers bureau: Eli Lilly, AbbVie and Pfizer, Consultant of: Eli Lilly, AbbVie and Pfizer, Nils Feltelius Employee of: Nils Feltelius is employed by the Medical Products Agency (MPA), which is a governmental body. The views in this abstract may not represent the views of the MPA, Helena Forsblad-d’Elia: None declared, Alf Kastbom Employee of: Former employee of Sanofi, Lars Klareskog: None declared, Elisabet Lindqvist: None declared, Ulf Lindström: None declared, Carl Turesson Speakers bureau: Roche, AbbVie and Pfizer, Consultant of: Roche, Grant/research support from: Research grant from Bristol-Myers Squibb, Christopher Sjowall: None declared, Johan Askling Grant/research support from: PI for agreements between Karolinska Institutet and Abbvie, BMS, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and Sanofi for safety monitoring of anti-rheumatic therapies (ARTIS).