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Introduction The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (SAC/VAL) has shown benefit in patients with symptomatic heart failure (HF), including those naïve to renin–angiotensin–aldosterone system inhibitor (RAASi) therapy, and is considered the preferred RAASi for chronic HF. Real-world data on ARNI, specifically in RAASi-naïve patients, are limited. This study compared real-world outcomes of ARNI (SAC/VAL) vs. angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy in RAASi-naïve patients with HF and reduced ejection fraction (HFrEF). Methods This retrospective cohort study included de-identified data on RAASi-naïve patients with HFrEF (left ventricular ejection fraction ≤ 40%) who had newly initiated SAC/VAL or ACEi/ARB between July 1, 2015, and March 31, 2019, from the Optum® Electronic Health Records database in the US. New SAC/VAL users were propensity score matched 1:2 with new ACEi/ARB users by pre-selected characteristics. One-year post-index rates of all-cause, HF, and cardiovascular hospitalizations and the composite of HF hospitalization or emergency room (ER) visits were measured using negative binomial regression. Time to first all-cause hospitalization, HF hospitalization, and composite of HF hospitalization or ER visits was measured using a subdistribution hazards model. Results The matched sample included 3059 new SAC/VAL and 6118 new ACEi/ARB users. Rates of all-cause hospitalization and composite of HF hospitalization or ER visits were significantly lower with SAC/VAL compared with ACEi/ARB (incidence rate ratio [95% confidence interval]: 0.87 [0.81–0.93] and 0.87 [0.81–0.94], respectively), whereas rates of HF hospitalizations and cardiovascular hospitalizations were similar (1.00 [0.91–1.11] and 0.94 [0.87–1.02], respectively). Time-to-event analyses also showed a similar trend. Conclusions In real-world clinical practice, RAASi-naïve patients with HFrEF initiating SAC/VAL were less likely to be hospitalized than those initiating ACEi/ARB, suggesting a potential for a reduced clinical and economic burden in these patients.

Aims Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality. We examined the impact of recurrent HF hospitalizations (HFHs) on cardiovascular (CV) mortality among patients with HF in Sweden. Methods and results Adults with incident HF were identified from linked national health registers and electronic medical records from 01 January 2005 to 31 December 2013 for Uppsala and until 31 December 2014 for Västerbotten. CV mortality and all‐cause mortality were evaluated. A time‐dependent Cox regression model was used to estimate relative CV mortality rates for recurrent HFHs. Assessment was also done for ejection fraction‐based HF phenotypes and for comorbid atrial fibrillation, diabetes, or chronic renal impairment. Overall, 3878 patients with HF having an index hospitalization were included, providing 9691.9 patient‐years of follow‐up. Patients were relatively old (median age: 80 years) and were more frequently male (55.5%). Compared with patients without recurrent HFHs, the adjusted hazard ratio (HR [95% confidence interval; CI]) for CV mortality and all‐cause mortality were statistically significant for patients with one, two, three, and four or more recurrent HFHs. The risk of CV mortality and all‐cause mortality increased approximately six‐fold in patients with four or more recurrent HFHs vs. those without any HFHs (HR [95% CI]: 6.26 [5.24–7.48] and 5.59 [4.70–6.64], respectively). Similar patterns were observed across the HF phenotypes and patients with comorbidities. Conclusions There is a strong association between recurrent HFHs and CV and all‐cause mortality, with the risk increasing progressively with each recurrent HFH.

BACKGROUND AND AIMS Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, with an estimated annual incidence of 25 per million. Patients with persistent proteinuria ≥ 1 g/day are at increased risk of disease progression, with 30% or more progressing to kidney failure within 10 years. Hematuria and proteinuria are among the most common clinical manifestations of IgAN. The aim of this analysis was to better understand the clinical characteristics of IgAN patients from Europe, Asia and the USA, at the time of diagnosis. METHOD A retrospective analysis was conducted using data from the Adelphi IgAN Disease Specific Programme (DSP), a cross-sectional survey of IgAN-treating nephrologists in EU4 (France, Germany, Italy, UK), USA, China and Japan between June and October 2021. Nephrologists completed structured forms administered via online links for successive patients presenting with IgAN in their practice. The forms included demographic and clinical information including signs, symptoms and lab values amongst others. RESULTS A total of 269 nephrologists completed records for 1685 patients in this survey. Mean patient age was 43.3 years, and most were male (58%). The diagnosis was confirmed by biopsy in 86% of the patients. The mean eGFR at diagnosis ranged from 58.1 (median 55.5) in the USA to 78.3 (median 79.0) mL/min/1.73 m2, in China and Japan. Mean proteinuria ranged from 2.7 (median 2.0) in the USA to 3.4 (median 2.1) g/day in EU4 (Table 1). The main clinical signs at diagnosis were proteinuria (75%) and visible hematuria (63%). Edema and fatigue were reported in 38% and 27% of patients; 10% and 9% of patients reported appetite loss and sleep problems. A sizable proportion of patients (31%) also experienced pain in various parts of the body. CONCLUSION This comprehensive study of IgAN patients across varied geographies presents evidence that patients experience substantial symptomatic and clinical burden at diagnosis, irrespective of the region. The relatively high levels of proteinuria and low eGFR levels, especially in the USA, suggest that the disease is often severe and advanced by the time of diagnosis. Facilitating early diagnosis of IgAN—perhaps through better recognition of clinical signs and symptoms—could be beneficial in optimizing early treatment and preventing disease progression.

Aims Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality post‐diagnosis. Here, we examined the impact of recurrent HF hospitalization (HFH) on cardiovascular (CV) and all‐cause mortality among HF patients. Methods and Results Adult HF patients identified in the Clinical Practice Research Datalink with a first (index) hospitalization due to HF recorded in the Hospital Episode Statistics data set from January 2010 to December 2014 were included. Patients were followed up until death or end of study (December 2017). CV mortality as primary and as any reported cause and all‐cause mortality were evaluated. An extended Cox regression model was used for reporting adjusted relative CV mortality rates for time‐dependent recurrent HFHs. Overall, 8603 HF patients with an index hospitalization were included, providing 15 964 patient‐years of follow‐up. Patients were relatively old (median age: 80 years) and were mostly male (54.6%), with main co‐morbidities being hypertension and atrial fibrillation. Recurrent HFHs occurred one, two, three, and more than four times in 1561 (18.2%), 518 (6.02%), 206 (2.4%), and 153 (1.8%) patients, respectively. The median time to mortality was 215 (38–664) days for 50.8% of patients who died for any cause during the study period and 139 (27–531) days for 31.3% who died with CV reasons as primary cause. Compared with those of patients without recurrent HFHs, the adjusted hazard ratios (95% CI) for CV mortality as primary cause were 2.65 (2.35–2.99), 3.69 (3.06–4.43), 5.82 (4.48–7.58), and 5.95 (4.40–8.05) for those with one, two, three, and more than four recurrent HFHs. Conclusions There is a strong association between recurrent HFH and CV mortality, with the risk increasing progressively with each recurrent HFH.

Objectives To summarize cost-effectiveness (CE) evidence of sacubitril/valsartan for the treatment of heart failure (HF) patients with reduced ejection fraction (HFrEF). The impact of different modeling approaches and parameters on the CE results is also described. Methods We conducted a systematic literature review using multiple databases: Embase®; MEDLINE®; MEDLINE®-In Process; NIHR CRD database including DARE, NHS EED, and HTA databases; and the Cost Effectiveness Analysis registry. We also reviewed HTA countries’ websites to identify CE reports of sacubitril/valsartan, published up to 25-July-2021. Articles published in English as full-texts, conference-abstracts, or HTA reports were included. Results We included 44 CE models [39 from 37 publications (22 full-texts; 15 conference-abstracts) and 5 HTAs; Europe, n = 20; North and South Americas, n = 14; Asia and Australia, n = 10]. Most models adopted a Markov structure with constant transition probabilities of events (n = 27) or a mix of Markov and regression-based models (n = 16), with variations in structural assumptions and chosen parameters. Study authors concluded sacubitril/valsartan to be a cost-effective therapy in 37/41 models in chronic HFrEF patients and 2/3 models in hospitalized patients stabilized after an acute decompensation for HF. CE models showing sacubitril/valsartan not to be a cost-effective treatment generally modeled a shorter time horizon. Effect of sacubitril/valsartan on cardiovascular and all-cause mortality, cost, duration of effect and time horizon was the main model drivers. Conclusions Most evidence indicated sacubitril/valsartan is cost-effective in HFrEF. The use of a lifetime horizon is recommended in future models as HF is a chronic disease. Data on the CE of sacubitril/valsartan in the inpatient setting were limited and further research is warranted.

Ana Filipa Fonseca,1 Raquel Lahoz,1 Clare Proudfoot,1 Stefano Corda,1 Emil Loefroth,1 James Jackson,2 Sarah Cotton,2 Rachel Studer1 1Novartis Pharma AG, Basel, Switzerland; 2Adelphi Real World, Bollington, UKCorrespondence: Ana Filipa FonsecaReal World Evidence Group, Cardio-Renal-Metabolic Franchise, Novartis Pharma AG, Novartis Campus, Basel, CH-4002, SwitzerlandTel: +41 (0) 793489979Email ana_filipa.fonseca@novartis.comPurpose: To characterize symptoms, clinical burden, and health-related quality of life (HRQoL) among women and men with heart failure (HF) with a left ventricular ejection fraction (LVEF) of ≤ 60% in Europe.Patients and Methods: A real-world cross-sectional study was conducted in France, Germany, Italy, Spain, and United Kingdom from June to November 2019. Patient record forms were completed by 257 cardiologists and 158 general practitioners for consecutive patients with HF. The same patients were invited to complete a questionnaire comprising patient-reported outcomes: the Minnesota Living with Heart Failure Questionnaire (MLHFQ), five-level five-dimension EuroQol questionnaire (EQ-5D-5L), Visual Analogue Scale (VAS), and Work Productivity and Activity Impairment questionnaire.Results: The mean age of 804 patients (men, n=517; women, n=287) was 68.6 years (men, 67.8 years; women, 70.2 years; p=0.0022). The mean LVEF was 44.7% (men, 43.6%; women, 46.8%; p< 0.0001). Patients reported dyspnoea when active (overall, 55.7%; men, 56.0%; women, 55.3%), fatigue/weakness/faintness (34.5%; men, 32.9%; women, 37.2%), and oedema (20.3%; men, 18.7%; women, 23.1%) as the most troublesome HF symptoms. Overall, 54.1% of patients reported low mood/depression (men, 50.8%; women, 60.1%). The overall MLHFQ mean score was higher (ie, poorer HRQoL) among women vs men (37.9 vs 34.6; p=0.0481). MLHFQ was consistently higher (ie, poorer HRQoL) for women vs men across the physical (18.6 vs 16.6; p=0.0041) and emotional (9.4 vs 7.9; p=0.0021) scoring domains. Mean EQ-5D utility (0.69 vs 0.75; p=0.0046) and VAS scores (55.4 vs 61.3; p< 0.0001) were lower among women compared with men. Overall, 23.4% of patients were hospitalized owing to HF in the previous year (men, 22.7%; women, 24.6%). Patients reported 43.2% activity impairment due to HF (men, 41.6%; women, 46.4%; p=0.01).Conclusion: HF causes a substantial burden on patients, with a greater burden among women vs men. This gender-related difference is consistent with other HF studies, warranting further research to understand the underlying reasons.Keywords: burden, gender, heart failure, health-related quality of life, real-world, work productivity

Introduction Assess the cost-effectiveness (US healthcare payer perspective) of sarilumab subcutaneous (SC) 200 mg + methotrexate versus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or targeted DMARD + methotrexate for moderate-to-severe rheumatoid arthritis (RA) in adults with inadequate response to methotrexate. Methods Microsimulation based on patient profiles from MOBILITY (NCT01061736) was conducted via a 6-month decision tree and lifetime Markov model with 6-monthly cycles. Treatment response at 6 months was informed by a network meta-analysis and based on American College of Rheumatology (ACR) response. Responders: patients with ACR20 response who continued with therapy; non-responders: ACR20 non-responders who transitioned to the subsequent treatment. Utilities and quality-adjusted life-years (QALYs) were estimated via mapping 6-month ACR20/50/70 response to relative change in Health Assessment Questionnaire Disability Index score (short term) and based on published algorithms (long term). Direct costs considered drugs (wholesale acquisition costs), administration and routine care. Results Lifetime QALYs and costs for treatment sequences on the efficiency frontier were 3.43 and $115,019 for active csDMARD, 5.79 and $430,918 for sarilumab, and 5.94 and $524,832 for etanercept (all others dominated). Sarilumab was cost-effective versus tocilizumab and csDMARD (incremental cost-effectiveness ratios of $84,079/QALY and $134,286/QALY). Probabilistic sensitivity analysis suggested comparable costs and slightly improved health benefits for sarilumab versus tocilizumab, irrespective of threshold. Conclusion In patients with moderate-to-severe RA, sarilumab 200 mg SC every 2 weeks + methotrexate can be considered a cost-effective treatment option, with lower costs and greater health benefits than alternative treatment sequences (+ methotrexate) beginning with adalimumab, certolizumab, golimumab and tofacitinib and below commonly accepted cost-effectiveness thresholds against tocilizumab + methotrexate or csDMARD active treatment. Funding Sanofi and Regeneron Pharmaceuticals, Inc. Electronic supplementary material The online version of this article (10.1007/s12325-019-00946-1) contains supplementary material, which is available to authorized users.

Objective.We evaluated the effect of sarilumab on patient-perceived impact of rheumatoid arthritis (RA) using the 7-domain RA Impact of Disease (RAID) scale.Methods.Two phase III, randomized, controlled trials of sarilumab in patients with active, longstanding RA were analyzed: (1) sarilumab 150 mg and 200 mg every 2 weeks plus conventional synthetic disease-modifying antirheumatic drugs (+csDMARD) versus placebo + csDMARD [TARGET (NCT01709578)]; and (2) sarilumab 200 mg versus adalimumab (ADA) 40 mg monotherapy [MONARCH (NCT02332590)]. Least-squares mean (LSM) differences in RAID total score (range 0–10) and 7 key RA symptoms, including pain and fatigue (baseline to Weeks 12 and 24), were compared. “Responders” by RAID total score were defined by improvements from baseline ≥ minimal clinically important difference (MCID), and ≥ patient-acceptable symptom-state (PASS) at endpoint.Results.Sarilumab 150 mg and 200 mg + csDMARD were nominally superior (p < 0.05) versus placebo + csDMARD and 200 mg sarilumab versus ADA 40 mg in LSM differences for RAID total score at weeks 12 (−0.93 and −1.13; −0.49, respectively) and 24 (−0.75 and −1.01; −0.78), and all effects of RA (except functional impairment in MONARCH Week 12). Effects were greater in physical domains (e.g., pain) than mental domains (e.g., emotional well-being). More patients receiving sarilumab versus placebo or ADA reported improvements ≥ MCID and PASS in total RAID scores at both assessments.Conclusion.Based on the RAID, sarilumab + csDMARD or as monotherapy reduced the effect of RA on patients’ lives to a greater extent than placebo + csDMARD or ADA monotherapy. (ClinicalTrials.gov: NCT01709578 and NCT02332590)

Introduction To evaluate the comparative efficacy and safety of subcutaneous sarilumab 200 mg monotherapy administered every 2 weeks (q2w) versus other monotherapies of biologic, targeted and conventional synthetic disease-modifying antirheumatic drugs (bDMARDs, tsDMARDs, csDMARDs) at recommended doses for treatment of rheumatoid arthritis in patients who are intolerant of or inadequate responders to csDMARDs (csDMARD-IR). Methods A systematic literature review and network meta-analysis (NMA) were conducted on 24-week efficacy outcomes: Health Assessment Questionnaire Disability Index (HAQ-DI) score, American College of Rheumatology (ACR) 20/50/70 criteria, and European League Against Rheumatism Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28)

Raquel Lahoz,1 Clare Proudfoot,2 Ana Filipa Fonseca,1 Emil Loefroth,1 Stefano Corda,3 James Jackson,4 Sarah Cotton,4 Rachel Studer1 1Real World Evidence, Cardiovascular, Renal and Metabolism Franchise, Novartis Pharma AG, Basel, Switzerland; 2Health Economics and Outcomes Research, Cardiovascular, Renal and Metabolism Franchise, Novartis Pharma AG, Basel, Switzerland; 3Global Medical Affairs, Cardiovascular, Renal and Metabolism Franchise, Novartis Pharma AG, Basel, Switzerland; 4Real World Research, Adelphi Real World, Bollington, UKCorrespondence: Raquel LahozReal World Evidence and Data Science, Cardio-Renal-Metabolic Franchise, Novartis Pharma AG, Asklepios 8-4, Basel, CH-4002, SwitzerlandTel +41 79 535 99 30Email raquel.lahoz@novartis.comPurpose: To assess the burden among caregivers of patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤ 60%. The burden by New York Heart Association (NYHA) functional class was also characterized.Patients and Methods: A cross-sectional study was conducted in France, Germany, Italy, Spain, and UK from June to November 2019. Patient record forms were completed by 257 cardiologists and 158 general practitioners for consecutive HF patients. Caregivers who accompanied the patient to their consultation completed a caregiver self-completion survey voluntarily, which included the Family Caregiver Quality of Life Questionnaire (FAMQOL) and 5-level 5-dimension EuroQol questionnaire (EQ-5D-5L).Results: We analyzed 361 caregivers of patients with HF (NYHA class I, n=41; II, n=212; III IV, n=108). Mean age of caregivers was 58.8 years (NYHA I/II/III–IV: 59.1/60.8/54.6 years; p=0.0029), with majority being females (73.1%). Caregivers spent on average 19.8 hours/week caring for a HF patient, which increased with increase in NYHA class (I/II/III–IV: 11.8/18.1/25.9 hours/week; p=0.0094). Caregivers (24.1%) reported providing emotional support/encouragement to patients as the most troublesome/inconvenient caregiving activity (no significant difference across NYHA class). Nearly one-third of caregivers experienced stress (NYHA I/II/III–IV: 17.1%/28.8%/40.7%; p=0.0111) and anxiety (26.8%/24.1%/39.8%; p=0.0127) due to caregiving burden. The overall FAMQOL mean score decreased significantly (poorer QoL) with increase in NYHA class (I/II/III–IV: 58.1/56.3/52.2; p=0.0069). A trend of decreasing scores with increasing NYHA class was observed across physical, emotional, and social domains (each p≤ 0.012).Conclusion: Caregivers of HF patients with LVEF ≤ 60% experienced a significant burden, which was higher among caregivers of patients with more severe and symptomatic disease.Keywords: burden, caregiver, heart failure, NYHA class, quality of life, real world evidence

Background: The clinical development program of sacubitril/valsartan (sac/val) for heart failure with reduced ejection fraction (HFrEF) only included a very limited number of patients being naive to prior angiotensin converting enzyme inhibitors (ACEis) or angiotensin II receptor antagonists (ARBs). Recent studies support the use of sac/val in hospitalised HF patients without prior ACEis/ARBs. This study aims to compare HF patients newly prescribed either sac/val or ACEis/ARBs. Methods: Retrospective non-interventional cohort study describing two mutually exclusive adult patient cohorts diagnosed with HFrEF either initiating sac/val or ACEis/ARBs. All patients were naive to both sac/val and ACEis/ARBs for 12 months prior to the first prescription. All patients had a left ventricular ejection fraction (LVEF) ≤40%. Patients were identified any time between 1 st July 2015 and 31 st Dec 2018 in the Optum® de-identified EHR dataset from providers across the continuum of care. Results: 2,414 patients were initiated on sac/val, 36,563 on ACEis/ARBs. Mean age was 66.1 (SD 12.9) and 67.2 years (SD 13.7) for sac/val and ACEis/ARBs users, respectively. Sac/val patients were more likely to be male: 70.8% vs 67.2% (p Conclusions: This real-world study indicates that sac/val tends to be newly prescribed to younger, male HFrEF patients with lower LVEF and a higher proportion of cardio resynchronization therapy devices compared with patients newly initiated on ACEis/ARBs. The prevalence of ischemic heart disease is similar between the groups.

Background and purpose Heart Failure (HF) is associated with symptoms such as dyspnoea and fatigue which can impact patients' health related quality of life (HRQoL). This study aimed to characterize and assess the HRQoL of patients with HF and left-ventricular ejection fraction (LVEF) Methods A cross-sectional study of patients with HF was conducted in France, Germany, Italy, Spain and United Kingdom. Patient record forms (PRFs) were completed by 257 cardiologists and 158 general practitioners (GPs) for consecutively consulting patients. The same patients were invited to provide patient-reported outcomes including self-completion questionnaires, Minnesota Living with Heart Failure Questionnaire (MLHFQ) and EQ-5D-5L VAS. Results 204 HF patients with LVEF Conclusions The HRQoL of all HF patients with LVEF ≤60% appears impacted, while those with LVEF Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

Background and purpose The majority of patients with heart failure (HF) have difficulties in independently carrying out activities of daily living and hence, require support from caregivers (CGs). This study assessed the quality of life (QoL) of CGs of HF patients with sub-normal LVEF (≤60%). Methods A cross-sectional survey of HF patients and their CGs was conducted in France, Germany, Italy, Spain and the UK. Cardiologists and primary care physicians completed patient record forms (PRF) between June and November 2019. Caregivers of the same patients were invited to complete a caregiver self-completion survey, which included the Family Caregiver QoL Scale (FAMQOL) and EQ-5D. Patient demographics were derived from PRFs. Results 361 CGs (73.1% female, mean age: 58.8 yrs) and HF patients (39.9% female, mean age: 71.2 yrs) were included. 58.2% of the CGs were spouses, 23.4% a child of the patient. On average, CGs devoted 20 hrs/week in the care of HF patients; this CG time increased from 12 to 26 hrs/week with NYHA class I to III/IV of the HF patient. Further, anxiety/stress was experienced overall by 29/31% of CGs which increased from 27/17% for NYHA I to 40/41% for NYHA III/IV of the HF patient (Table 1). Conclusions Caregivers of patients with HF and LVEF ≤60% spend a significant amount of time to provide daily support to HF patients. Patients with progressive disease were older, more polymorbid and had a higher disease duration. These factors likely contributed towards increased caregiver burden of HF patients with increased NYHA class. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

Background and purpose Heart failure (HF) is one of the leading causes of hospitalization among older adults and is associated with a large burden of disease for the individual, the patient's family, healthcare systems, and society. This study assessed the burden of hospitalizations in patients with HF with LVEF >40% in the United States (US). Methods This retrospective, non-interventional study identified adult patients with incident or prevalent HF in Optum® de-identified Electronic Health Record (EHR) dataset (2007–2018) between 01/01/2013 and 31/12/2017. Optum's longitudinal EHR repository is derived from dozens of healthcare provider organizations in the US, that include more than 700 Hospitals and 7000 Clinics; treating >95 million patients receiving care in the US. Patients were followed for up to 1 year or until last active date whichever occurred first. Comorbidities, all-cause hospitalizations (AcH) and primary cause HF hospitalizations (HFH) were analysed. Results 120,606 patients with HF and LVEF >40% (54% female) with a mean (SD) age of 71 (13) yrs were included, representing 80,324.74 patient-yrs follow-up (days). Common comorbidities were hypertension (91.8%), ischemic heart disease (IHD, 71.4%), atrial fibrillation (AF, 54.8%), renal disease (54.1%), type 2 diabetes (T2D, 50.7%), obesity (44.6%) and anemia (39%). Comorbidities including IHD (72.9% vs. 68.4%), AF (56.4% vs. 51.6%) and T2D (51.1% vs. 49.9%) were more often recorded in patients with LVEF >40-≤60% than >60% cohort while hypertension (91.6% vs. 92.2%), renal disease (53.8% vs. 54.6%), obesity (43.9% vs. 46.1%) and anemia (38.1% vs. 40.9%) had significantly higher frequency in the LVEF >60% cohort. The annualized AcH rate for patients with LVEF>40% was 1.44 and annualized HFH rate was 0.24 with a median length of stay of 3 and 4 days, respectively. Annualized hospitalization rates were significantly higher for women than men (both AcH and HFH). AcH rates were significantly higher and HFH rates were significantly lower for patients with LVEF>60% compared with LVEF >40-≤60. Conclusions This study demonstrates that patients with HF and LVEF >40% experience significant burden from comorbidities and hospitalizations from any-cause and for HF. The hospitalization rates are higher in women (both AcH and HFH) or patients with LVEF >60% (AcH only). Further focus on reduction of hospitalizations and interdisciplinary management of patients with HF should be warranted. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

Background and purpose Sacubitril/valsartan (sac/val), an angiotensin receptor neprilysin inhibitor, reduces the risk for cardiovascular (CV) death or hospitalization for heart failure (HF) in HF with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are approved in patients with type 2 diabetes (T2D) and have shown to reduce the CV risk in T2D patients with established CV or at risk of CV disease. The SGLT2i dapagliflozin has shown to improve outcomes in patients with chronic HFrEF, with or without T2D, when used in addition to standard of care including sac/val. As the use of SGLT2i in HF evolves, and given the large overlap of HF and T2D populations, it is of interest to understand the population with concomitant use of sac/val and SGLT2i. This study describes the clinical characteristics of patients treated concomitantly with sac/val and SGLT2i or concomitantly with sac/val and dipeptidyl peptidase-4 inhibitors (DPP4i) or glucagon-like peptide-1 receptor agonists (GLP1), two comparable second line anti-diabetic drug classes. Methods This retrospective non-interventional study describes two mutually exclusive adult patient cohorts diagnosed with HF and T2D concomitantly prescribed sac/val and SGLT2i (cohort 1), or concomitantly prescribed sac/val and DDP4i/GLP1 (cohort 2). The index date was defined as the first date of concomitant use with prescriptions overlapping a minimum of 21 days. Patients were identified any time between 1/1/2015 and 30/6/2019 in the Optum® de-identified electronic health record (EHR) data from providers across the continuum of care. Results 2.3 million HF patients were identified, and 41.6% had a T2D diagnosis. 560 patients were concomitantly prescribed sac/val and SGLT2i (cohort 1) and 1,566 concomitantly sac/val and DDP4/GLP1 (cohort 2). There was a higher proportion of females in cohort 2 (35.0% vs 27.9%). Mean age was higher in cohort 2 (66.4 vs 61.4 years). The mean estimated glomerular filtration rate was 85.93 (SD 23.43) ml/min/1.73m2 (cohort 1) and 72.10 (Std. 27.11) ml/min/1.73m2 (cohort 2). The proportion of stage 3 CKD (30 ml/min/1.73m2) was 11.8% (cohort 1) and 24.4% (cohort 2). Mean systolic blood pressure was similar, 120 mmHg (cohort 1) and 122 mmHg (cohort 2). Mean hemoglobin was 13.60 g/dl (cohort 1) and 12.43 g/dl (cohort 2). Median (IQR) NT-proBNP differed between the two cohorts, 914 (2154) pg/ml (cohort 1) and 2,290 (5,301) pg/ml (cohort 2) but with complete values available in only 17.7 and 19.0% of each cohort. Conclusions This descriptive analysis of concomitant prescription of sac/val and SGLT2i or DPP4/GLP1 highlights differences in the clinical characteristics between the two cohorts. The patients treated with sac/val and SGLT2i start with a more favorable clinical profile compared to the patients treated with sac/val and DPP4/GLP1. Further analyses are needed to determine if these differences are driven by age, gender or other factors. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

Background and purpose Heart Failure (HF) is associated with symptoms such as dyspnoea and fatigue, however, physicians and patients' perception of HF symptoms may differ. This study aimed to explore the extent to which symptoms experienced by patients with HF are recognized by their physician and if physicians over- or under-reported HF symptoms. Methods A cross-sectional study of patients with HF was conducted in France, Germany, Italy, Spain and the United Kingdom (Disease Specific Programme in HF by Adelphi Real World). Patient record forms (PRFs) were completed by 257 cardiologists and 158 general practitioners (GPs) for consecutively consulting patients. The same patients were invited to complete a patient self-completion questionnaire (PSC). Only responses from PRFs with an associated PSC were analysed. Concordance was calculated as agreement between PSC and PRF when both were aligned with the presence or absence of HF symptom out of the total number of matched pairs. The over- or under-reporting of the occurrence of symptoms by the physicians relative to patient-reported symptoms was also calculated by taking the patient perspective and evaluating how often a patient-reported symptom was not recognized in the PRF (physician under-reporting) and vice versa (physician over-reporting). Results 792 HF patients with LVEF ≤60% (35% female) with a mean age of 68.6 years were included. 58% of PRFs were completed by cardiologists and 42% by GPs. The most common patient reported HF symptoms were dyspnoea when active (74%), fatigue (59%) and oedema (42%) (Figure 1a). Overall, a high concordance rate was observed in reporting of HF symptoms between patients and their physicians ranging between 75% for fatigue and 94% for gastric/intestinal discomfort (Figure 1b). In non-concordant cases, most symptoms were under-reported by physicians, except dyspnoea when active and fatigue/weakness which were over-reported in 34/33%, respectively. The frequency of over-reporting of HF symptoms by the physicians was higher for more frequently patient reported symptoms while under-reporting was observed in less frequently reported symptoms such as gastric/intestinal discomfort, swelling of abdomen, inability to sleep, paroxysmal nocturnal dyspnoea and orthopnoea (Figure 1c). Conclusions The current study suggests that there is an overall high concordance between physicians and patients in reporting HF symptoms. However, while physicians were aware of the most prevalent HF symptoms experienced by patients, it was more common to under-report the less frequent HF symptoms. Ensuring patient education and good communication between patients and their physicians might help better and earlier identification of HF symptoms. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

Background: PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril in patients with heart failure with reduced ejection fraction (HFrEF). However, patients in clinical practice may differ in their characteristics and overall risk compared with patients in clinical trials, and additional outcomes can be observed in real world (RW). Hence, a systematic review was conducted to identify and describe RW data on sac/val. Methods: RW studies evaluating the effects of sac/val in adult patients with HFrEF with a sample size ≥100 were identified via MEDLINE® and Embase® from 2015 to January 2020. Citations were screened, critically appraised and relevant data were extracted. Results: A total of 68 unique studies were identified. Nearly half of the studies were conducted in Europe (n = 34), followed by the US (n = 15) and Asia (n = 11). Median follow-up period varied from 1 to 19 months. Mean age ranged between 48.7 and 79.0 years; patients were mostly male and in New York Heart Association (NYHA) functional class II/III, and mean left ventricular ejection fraction varied between 23%and 38%. Of studies performing comparisons, most reported superior efficacy of sac/val in reducing the risk of HF hospitalisations, all-cause hospitalisations, and all-cause mortality as compared to standard-of-care. Many studies reported significant improvements in NYHA functional class and reduction in biomarker levels post sac/val. Hypotension and hyperkalaemia were the most frequently reported adverse events. Conclusions: This comprehensive overview of currently available RW evidence on sac/val complements the evidence from randomised controlled trials, substantiating its effectiveness in heterogeneous real-world HF populations.

Cheryl P Ferrufino,1 Julie Munakata,1 Wenhui Wei,2 Clare Proudfoot,3 Andreas Kuznik,4 Susan H Boklage,4 Chieh-I Chen4 1IQVIA, Fairfax, VA, USA; 2Sanofi, Bridgewater, NJ, USA; 3Sanofi, Guildford, UK; 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY,USA Objective: To estimate the 5-year budget impact (BI) on a US health plan of introducing sarilumab – a human immunoglobulin G1 anti-IL-6 receptor α monoclonal antibody – as combination treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or monotherapy in patients with moderate-to-severe rheumatoid arthritis (RA).Methods: BI analysis was conducted from a commercial payer perspective. Treatment-eligible populations included adult patients with moderate-to-severe RA and inadequate response (IR) to csDMARDs or tumor necrosis factor (TNF)-α inhibitors-IR. All licensed biologic treatments recommended by the American College of Rheumatology guidelines were included.Results: For a hypothetical plan of one million members, 409 csDMARD-IR and 345 TNF-IR patients were annually eligible for combination therapy and 226 csDMARD and TNF-IR patients for monotherapy with sarilumab. Based on 2018 US direct treatment costs, the introduction of sarilumab was estimated to save $526,424, $322,637 and $264,306 over 5 years for csDMARD-IR combination therapy patients, TNF-IR combination therapy patients, and csDMARD-IR/TNF-IR monotherapy patients, respectively. As sarilumab absorbed a greater market share over the horizon, annual savings increased from years 1 to 5, $28,610 (–0.14%) to $194,646 (–0.83%) in csDMARD-IR, $16,986 (–0.11%) to $120,893 (–0.67%) in TNF-IR, and $14,256 (–0.13%) to $98,040 (–0.79%) in monotherapy. One-way sensitivity analyses revealed that the model was most sensitive to variations in sarilumab adherence.Conclusion: Total cost savings of introducing sarilumab to a health-care plan accrued from years 1 to 5, attributable to the lower treatment cost, stable dosing paradigm, and price parity for the two available doses (150 and 200 mg every 2 weeks) compared with alternative biologic DMARDs that have substantial variability in dose titration/schedules. Keywords: treatment costs, disease-modifying anti-rheumatic drug, IL-6 inhibitorCorrigendumfor this paper has been published

Objective To estimate the 5-year budget impact (BI) on a US health plan of introducing sarilumab – a human immunoglobulin G1 anti-IL-6 receptor α monoclonal antibody – as combination treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or monotherapy in patients with moderate-to-severe rheumatoid arthritis (RA). Methods BI analysis was conducted from a commercial payer perspective. Treatment-eligible populations included adult patients with moderate-to-severe RA and inadequate response (IR) to csDMARDs or tumor necrosis factor (TNF)-α inhibitors-IR. All licensed biologic treatments recommended by the American College of Rheumatology guidelines were included. Results For a hypothetical plan of one million members, 409 csDMARD-IR and 345 TNF-IR patients were annually eligible for combination therapy and 226 csDMARD and TNF-IR patients for monotherapy with sarilumab. Based on 2018 US direct treatment costs, the introduction of sarilumab was estimated to save $526,424, $322,637 and $264,306 over 5 years for csDMARD-IR combination therapy patients, TNF-IR combination therapy patients, and csDMARD-IR/TNF-IR monotherapy patients, respectively. As sarilumab absorbed a greater market share over the horizon, annual savings increased from years 1 to 5, $28,610 (−0.14%) to $194,646 (−0.83%) in csDMARD-IR, $16,986 (−0.11%) to $120,893 (−0.67%) in TNF-IR, and $14,256 (−0.13%) to $98,040 (−0.79%) in monotherapy. One-way sensitivity analyses revealed that the model was most sensitive to variations in sarilumab adherence. Conclusion Total cost savings of introducing sarilumab to a health-care plan accrued from years 1 to 5, attributable to the lower treatment cost, stable dosing paradigm, and price parity for the two available doses (150 and 200 mg every 2 weeks) compared with alternative biologic DMARDs that have substantial variability in dose titration/schedules.

Introduction After a patient with rheumatoid arthritis (RA) fails tumor necrosis factor inhibitor (TNFi) treatment, clinical guidelines support either cycling to another TNFi or switching to a different mechanism of action (MOA), but payers often require TNFi cycling before they reimburse switching MOA. This study examined treatment persistence, cost, and cost per persistent patient among MOA switchers versus TNFi cyclers. Methods This study of Commercial and Medicare Advantage claims data from the Optum Research Database included patients with RA and at least one claim for a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between January 2012 and September 2015 who changed to another TNFi or a different MOA therapy (abatacept, tocilizumab, or tofacitinib) within 1 year. The index date was the date of the change in therapy. Treatment persistence was defined as no subsequent switch or 60-day gap in therapy for 1 year post-index. RA-related costs included plan-paid and patient-paid amounts for inpatient, outpatient, and pharmacy claims. Medication costs included index and post-index costs of TNFi and different MOA therapies. Results There were 581 (38.3%) MOA switchers and 935 (61.7%) TNFi cyclers. The treatment persistence rate was significantly higher for MOA switchers versus TNFi cyclers (47.7% versus 40.2%, P = 0.004). Mean 1-year healthcare costs were significantly lower among MOA switchers versus TNFi cyclers for total RA-related costs ($37,804 versus $42,116; P

Despite a substantial number of treatment options in rheumatoid arthritis (RA) following tumor necrosis factor inhibitor (TNFi) inadequate response or intolerance (TNF-IR), a lack of clarity on the optimal approach remains. Sarilumab, a human monoclonal anti-interleukin-6 receptor alpha antibody, can be used as monotherapy or in combination with methotrexate or other conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) in TNF-IR patients.To conduct a cost-utility analysis from a U.S. health care system perspective for sarilumab subcutaneous 200 mg + methotrexate versus abatacept + methotrexate or a bundle of TNFi + methotrexate for treatment of adult patients with moderately to severely active RA and TNF-IR.Analysis was conducted via individual patient simulation based on patient profiles from the TARGET trial (NCT01709578); a 6-month decision tree was followed by lifetime semi-Markov model with 6-month cycles. Treatment response at 6 months, informed by network meta-analysis, was based on American College of Rheumatology (ACR) 20/50/70 criteria; patients achieving ≥ ACR20 continued with current therapy, and other patients moved to the next line of biologic DMARD therapy or conventional synthetic DMARD palliative treatment. Direct costs included wholesale acquisition drug costs and administration and routine care costs. Routine care costs and quality-adjusted life-years (QALYs) were estimated by predicting the Health Assessment Questionnaire Disability Index score based on treatment response and were imputed from published equations.Sarilumab + methotrexate dominated the TNFi bundle + methotrexate, achieving lower costs ($319,324 vs. $356,096) and greater effectiveness (4.27 vs. 4.15 QALYs), and was on the cost-efficiency frontier with abatacept + methotrexate ($360,211 and 4.29 QALYs). Abatacept + methotrexate was not cost-effective versus sarilumab + methotrexate. Scenario analyses indicated the results were robust; sarilumab + methotrexate became dominant against abatacept + methotrexate after reduced model horizon, minimum response based on ACR50 or ACR70, or time to discontinuation per treatment class. Sarilumab + methotrexate was also dominant versus the TNFi bundle; when class-specific time to treatment discontinuation was specified, sarilumab remained cost-effective with an incremental cost-effectiveness ratio of $36,894.Sarilumab + methotrexate can be considered an economically dominant (more effective, less costly) option versus a second TNFi + methotrexate; compared with abatacept + methotrexate, it is a less costly but less effective option for patients with moderately to severely active RA who have previously failed TNFi.This study was funded by Sanofi and Regeneron Pharmaceuticals. Kiss and Gal are employees of Evidera, which received consulting fees from Sanofi/Regeneron for conducting this study. Muszbek was employed by Evidera at the time of this study. Kuznik and Chen are current employees of and stockholders in Regeneron Pharmaceuticals. Fournier is an employee of and stockholder in Sanofi. Proudfoot is a former employee of and current stockholder in Sanofi and current employee and stockholder in ViiV Healthcare/GlaxoSmithKline. Michaud has received grant funding from Pfizer and the Rheumatology Research Foundation. The sponsors were involved in the study design, collection, analysis, and interpretation of data as well as data checking of information provided in the manuscript. The authors had unrestricted access to study data, were responsible for all content and editorial decisions, and received no honoraria related to the development of this publication.

Background Previous studies have suggested that recurrent heart failure hospitalizations (HFh) are a predictor of cardiovascular (CV) and all-cause mortality. Patients with atrial fibrillation (AF) or type 2 diabetes mellitus (T2DM) may be at increased risk. Purpose This real-world study examined the impact of recurrent HFh on CV mortality in subgroups of patients with (i) AF or (ii) T2DM in the UK. Methods Adult HF patients identified in the CPRD database with a first (index) hospitalization due to HF recorded in the HES dataset from 01/01/2010 to 31/12/2014 and with a claim for AF or T2DM (not mutually exclusive) within the year prior to the index hospitalization were included. Patients were followed until death, transfer out or end of study period (31/12/2017). CV death as primary cause and death due to any cause were evaluated. An extended Cox regression model was used for reporting adjusted relative CV mortality rates for time dependent recurrent HFh. Results 4585 (53.30%) HF patients with AF and 2344 (27.25%) HF patients with T2DM were included, providing 7846 and 4269 patient-years follow-up, respectively. Patients were relatively old (median [IQR] age of 81 [74–87] and 78 [70–84]) and majority were male (54.2% and 59.1%, respectively). All-cause and CV mortality rates are provided in the table. Compared with those without recurrent HFh, the adjusted hazard ratios (95% CI) for CV death for the AF group were 2.6 (2.3–3.1), 3.2 (2.5–4.1), 5.8 (4.1–8.1) and 6.9 (4.6–10.5) for 1, 2, 3 and ≥4 recurrent HFh, and for the T2DM group were 2.2 (1.7–2.8), 3.3 (2.3–4.7), 5.1 (3.3–8.1) and 3.9 (2.3–6.6), respectively. All-cause and CV mortality rates 0 Recurrent HFh 1 Recurrent HFh 2 Recurrent HFh 3 Recurrent HFh 4+ Recurrent HFh All patients AF n=3294 (71.8%) n=817 (17.8%) n=282 (6.2%) n=116 (2.5%) n=76 (1.2%) n=4585 (100.0%) Follow-up time (days) from respective recurrent HF hospitalization (median [IQR]) 345 [57–906] 118 [27–522] 80 [19–367] 54 [19–240] 126 [50–379] 254 [42–793] All-cause death (n (%)) 1755 (53.3%) 483 (59.1%) 159 (56.4%) 80 (69.0%) 46 (60.5%) 2523 (55.0%) CV death- primary cause (n (%)) 1059 (32.2%) 325 (39.8%) 109 (38.7%) 56 (48.3%) 34 (44.7%) 1583 (34.5%) T2DM n=1573 (67.1%) n=456 (19.5%) n=170 (7.3%) n=85 (3.6%) n=60 (2.6%) n=2344 (100.0%) Follow-up time (days) from respective recurrent HF hospitalization (median [IQR]) 360 [63–933] 198 [43–545] 68 [17–292] 106 [26–251] 160 [68–389] 267 [49–771] All-cause death (n (%)) 824 (52.4%) 248 (54.4%) 99 (58.2%) 51 (60.0%) 40 (66.7%) 1262 (53.8%) CV death – primary cause (n (%)) 501 (31.9%) 159 (34.9%) 69 (40.6%) 36 (42.4%) 26 (43.3%) 791 (33.8%) Conclusion Recurrent HFh are a strong predictor of CV death in the HF population with AF or with T2DM. The risk of CV and all-cause death increases with recurrent HFh in these subpopulations, highlighting the relevance of reducing hospitalizations in the management of HF patients with such comorbid conditions.

Marie Fournier,1 Chieh-I Chen,2 Andreas Kuznik,2 Clare Proudfoot,3 Usha G Mallya,4 Kaleb Michaud5,6 1Health Economics & Value Assessment, Sanofi France, Chilly-Mazarin, France; 2Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 3Sanofi, Guildford, UK; 4Sanofi, Bridgewater, NJ, USA; 5University of Nebraska Medical Center, Omaha, NE, USA; 6The National Databank for Rheumatic Diseases, Wichita, KS, USA Purpose: Treatment outcomes and direct medical costs were examined, from a US health payer perspective, of monotherapy with sarilumab 200 mg subcutaneous (SC) every 2 weeks (Q2W) vs adalimumab 40 mg SC Q2W/QW in adult patients with moderately to severely active rheumatoid arthritis who are intolerant of, inadequate responders to, or considered inappropriate candidates for continued methotrexate treatment.Patients and methods: Short-term analysis was based on 24-week wholesale acquisition costs of drugs and treatment response observed in the MONARCH Phase III trial (NCT02332590) per American College of Rheumatology (ACR) 20/50 criteria and European League Against Rheumatism (EULAR) Moderate/Good Disease Activity Score 28-joint count erythrocyte sedimentation rate. Long-term analysis, which also considered drug administration and routine care costs, was conducted via a 6-month decision tree and a 1- to 10-year Markov model with microsimulation of patient profiles from the MOBILITY Phase III trial (NCT01061736). Utilities and quality-adjusted life-years (QALYs) were estimated by mapping 6-month ACR levels to a relative change in Health Assessment Questionnaire – Disability Index score and via published algorithms.Results: For sarilumab and adalimumab, respectively, 24-week drug costs were $18,954 and $29,232, and costs per responder were $26,435 vs $50,055 on ACR20; $41,475 vs $98,425 on ACR50; and $22,511 vs $41,230 on EULAR Moderate/Good. Base case results at 10 years for total costs and QALYs were $176,977 and 2.75 for sarilumab and $212,136 and 2.61 for adalimumab, respectively. Sarilumab was consistently the more effective and cost-saving treatment across all short-term and long-term incremental analyses.Conclusion: Sarilumab monotherapy was the economically dominant treatment on incremental cost per responder and incremental cost per QALY compared with adalimumab monotherapy. These results were maintained within the sensitivity analyses. Keywords: treatment costs, disease-modifying anti-rheumatic drug, IL-6 inhibitor, rheumatoid arthritis, cost per responser

ObjectiveTo compare efficacy and safety of subcutaneous sarilumab 200 mg and 150 mg every 2 weeks plus conventional synthetic disease-modifying antirheumatic drugs (+csDMARDs) versus other targeted DMARDs+csDMARDs and placebo+csDMARDs, in inadequate responders to csDMARDs (csDMARD-IR) or tumour necrosis factor α inhibitors (TNFi-IR).MethodsSystematic literature review and network meta-analyses (NMA) conducted on 24 week efficacy and safety outcomes: Health Assessment Questionnaire Disability Index, modified total sharp score (mTSS, including 52 weeks), American College of Rheumatology (ACR) 20/50/70, European League Against Rheumatism Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28)Results53 trials were selected for NMA. csDMARD-IR: Sarilumab 200 mg+csDMARDs and 150 mg+csDMARDs were superior versus placebo+csDMARDs on all outcomes. Against most targeted DMARDs, sarilumab 200 mg showed no statistically significant differences, except superiority to baricitinib 2 mg, tofacitinib and certolizumab on 24 week mTSS. Sarilumab 150 mg was similar to all targeted DMARDs. TNFi-IR: Sarilumab 200 mg was similar to abatacept, golimumab, tocilizumab 4 mg and 8 mg/kg intravenously and rituximab on ACR20/50/70, superior to baricitinib 2 mg on ACR50 and DAS28ConclusionsResults suggest that in csDMARD-IR and TNFi-IR (a smaller network), sarilumab+csDMARD had superior efficacy and similar safety versus placebo+csDMARDs and at least similar efficacy and safety versus other targeted DMARDs+csDMARDs.

Objective To evaluate effects of the anti-interleukin-6 receptor monoclonal antibody sarilumab administered with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on patient-reported outcomes (PROs) in the TARGET trial in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitors (TNF-IR). Methods 546 patients (81.9% female, mean age 52.9 years) were randomised to placebo, sarilumab 150 or 200 mg subcutaneously every 2 weeks + csDMARDs. PROs included patient global assessment (PtGA); pain and morning stiffness visual analogue scales; Health Assessment Questionnaire Disability Index (HAQ-DI); Short Form-36 Health Survey (SF-36); FACIT-Fatigue (FACIT-F); Work Productivity Survey-Rheumatoid Arthritis (WPS-RA) and Rheumatoid Arthritis Impact of Disease (RAID). Changes from baseline at weeks 12 and 24 were analysed using a mixed model for repeated measures; post hoc analyses included percentages of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values. Results Sarilumab + csDMARDs doses resulted in improvements from baseline at week 12 vs placebo + csDMARDs in PtGA, pain, HAQ-DI, SF-36 and FACIT-F that were maintained at week 24. Sarilumab improved morning stiffness and reduced the impact of RA on work, family, social/leisure activities participation (WPS-RA) and on patients9 lives (RAID). Percentages of patients reporting improvements ≥MCID and ≥ normative scores were greater with sarilumab than placebo. Conclusions In patients with TNF-IR RA, 150 and 200 mg sarilumab + csDMARDs resulted in clinically meaningful patient-reported benefits on pain, fatigue, function, participation and health status at 12 and 24 weeks that exceeded placebo + csDMARDs, and were consistent with the clinical profile previously reported. Trial registration number NCT01709578; Results.