Sanofi (Austria)

AIMS: To determine the impact of gender on glycaemic control and hypoglycaemia in insulin-naïve patients with type 2 diabetes (T2DM). METHODS: Data were pooled from six randomized clinical trials of insulin glargine or NPH insulin in insulin-naïve, inadequately controlled patients. Female [n = 1251; mean glycated haemoglobin (HbA1c) level 8.99%, age 56.91 years, diabetes duration 9.84 years] and male patients (n = 1349; mean HbA1c 8.9%, age 57.47 years, diabetes duration 10.13 years) were started on and treated with insulin glargine or NPH insulin for 24-36 weeks. HbA1c and fasting blood glucose levels, percent achieving HbA1c target of <7% and insulin dose change were recorded. RESULTS: For both men and women, HbA1c levels were significantly reduced over time (p < 0.001); a significantly greater HbA1c reduction was observed in men than in women (-1.36 vs. -1.22; p = 0.002). Significantly fewer women achieved target HbA1c of <7% (p < 0.001). At the study end, women had a significantly higher insulin dose/kg than men (0.47 vs. 0.42 U/kg; p < 0.001). The incidence rates of severe and severe nocturnal hypoglycaemia were significantly higher in women (3.28% vs. 1.85%; p < 0.05 and 2.24% vs. 0.59%; p < 0.001, respectively). Women were more likely to experience severe hypoglycaemia [odds ratio (OR) 1.80; 95% confidence interval (CI) 1.08, 3.00; p = 0.02] and severe nocturnal hypoglycaemia (OR: 3.80; 95% CI 1.72, 8.42; p = 0.001). CONCLUSIONS: These observations confirm studies that found a smaller improvement in HbA1c and greater hypoglycaemia in women during insulin treatment. Physicians should be aware of the need to determine and closely monitor dosing, particularly in women, to optimize the balance between glycaemic control and hypoglycaemia risk.

BACKGROUND: HPV is a major cancer-causing factor in both sexes in the cervix, vulva, vagina, anus, penis, oropharynx as well as the causal factor in other diseases such as genital warts and recurrent respiratory papillomatis. In the context of the arrival of a nonavalent HPV vaccine (6/11/16/18/31/33/45/52/58), this analysis aims to estimate the public health impact and the incremental cost-effectiveness of a universal (girls and boys) vaccination program with a nonavalent HPV vaccine as compared to the current universal vaccination program with a quadrivalent HPV vaccine (6/11/16/18), in Austria. METHOD: A dynamic transmission model including a wide range of health and cost outcomes related to cervical, anal, vulvar, vaginal diseases and genital warts was calibrated to Austrian epidemiological data. The clinical impact due to the 5 new types was included for cervical and anal diseases outcomes only. In the base case, a two-dose schedule, lifelong vaccine type-specific protection and a vaccination coverage rate of 60% and 40% for girls and boys respectively for the 9-year old cohorts were assumed. A cost-effectiveness threshold of €30,000/QALY-gained was considered. RESULTS: Universal vaccination with the nonavalent vaccine was shown to reduce the incidence of HPV16/18/31/33/45/52/58 -related cervical cancer by 92%, the related CIN2/3 cases by 96% and anal cancer by 83% and 76% respectively in females and males after 100 years, relative to 75%, 76%, 80% and 74% with the quadrivalent vaccine, respectively. Furthermore, the nonavalent vaccine was projected to prevent an additional 14,893 cases of CIN2/3 and 2544 cases of cervical cancer, over 100 years. Depending on the vaccine price, the strategy was shown to be from cost-saving to cost-effective. CONCLUSION: The present evaluation showed that vaccinating 60% of girls and 40% of boys aged 9 in Austria with a 9-valent vaccine will substantially reduce the incidence of cervical cancer, CIN and anal cancer compared to the existing strategy. The vaccination strategies performed with the 9-valent vaccine in the current study were all found to be cost-effective compared to the current quadrivalent vaccination strategy by considering a cost-effectiveness threshold of 30,000€/QALY gained.

The International Agency for Research on Cancer acknowledges that HPV is a human carcinogen affecting both sexes. This study aimed to evaluate the public health impact of universal HPV vaccination in Austria, to assess its cost-effectiveness and to estimate the HPV prevalence reduction over time. Vaccinating 65% of 9-year-old boys and girls in Austria would result in a 70% decrease in HPV infections in both males and females, hereby avoiding 9500 cases of genital warts annually and 431 HPV 16/18-related cancers in males and females. This strategy would be cost effective with base case analysis of €26,701/quality-adjusted life year (QALY) gained for cervical cancer only, €15,820/QALY also including vaginal/vulvar cancers and genital warts, and €10,033/QALY also considering anal, oropharyngeal and penile cancers, with an incremental cost-effectiveness ratio ranging from €2500 to €21,000/QALY in sensitivity analyses. HPV circulation would be controlled hereby preventing subsequent HPV-related cancers.

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 inhibition can be an effective treatment in patients with primary hypercholesterolemia, particularly in cases with concomitant coronary heart disease, peripheral artery occlusive disease or cerebrovascular occlusive disease for secondary prevention after an acute atherosclerotic ischemic event. The primary objective of the PEARL-AT study was to assess effectiveness and safety of alirocumab in a real-world setting in Austria. METHODS: Non-interventional, prospective study conducted across Austria between September 2016 and July 2018. 113 patients, for whom the decision for treatment with alirocumab according to the Austrian Summary of Product Characteristics (SmPC) was made, were enrolled and were followed-up over 24 weeks. The primary endpoint of the study was the average change of low density lipoprotein cholesterol (LDL-C) levels by week 24. RESULTS: In total, 112 patients with at least one post-baseline visit were included. Alirocumab was initiated using 75 mg (57.1%) and 150 mg (42.9%) every two weeks. Average LDL-C levels decreased by 75.0 mg/dl at week 24 in 87 patients with available LDL-C at baseline and week 24 (in 25 patients LDL-C was missing at least at one time point). The mean relative change of LDL-C was -50.0% (median: 57.8%, SD: 28.4). Throughout the study, 46 adverse events were documented in 21 (18.6%) patients. The most frequent adverse events were gastrointestinal disorders. CONCLUSIONS: The present data indicate a good overall efficacy of alirocumab in a real-world Austrian population. Effectiveness and safety were both in line with the clinical trial program as well as previous real-world observations.

Background: PCSK9 antibodies strongly reduce LDL cholesterol. The effects of PCSK9 antibodies on triglyceride metabolism are less pronounced. The present study aimed to investigate in detail the effects of alirocumab on triglycerides, triglyceride-rich lipoproteins, and lipase regulators. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were two visits at the study site: the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. Fat-tolerance tests, nuclear magnetic resonance spectroscopy, and enzyme-linked immunosorbent assays were performed to analyze lipid metabolism. Results: A total of 21 participants underwent the first and second investigation. Among these, two participants only received alirocumab twice and 19 patients completed the trial per protocol. All of them had atherosclerotic vascular disease. There was no significant effect of alirocumab treatment on fasting triglycerides, post-prandial triglycerides, or lipoprotein-lipase regulating proteins. Total, large, and small LDL particle concentrations decreased, while the HDL particle concentration increased (all p &lt; 0.001). Mean total circulating PCSK9 markedly increased in response to alirocumab treatment (p &lt; 0.001). Whereas PCSK9 increased more than three-fold in all 19 compliant patients, it remained unchanged in those two patients with two injections only. Conclusion: Significant effects of alirocumab on triglyceride metabolism were not detectable in the ALIROCKS trial. The total circulating PCSK9 concentration might be a useful biomarker to differentiate non-adherence from non-response to PCSK9 antibodies.

Background: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p &lt; 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.

INTRODUCTION: Lixisenatide has been studied extensively in randomized clinical trials; however, data on its use in the real-life practice are scarce. METHODS: This study was a prospective, 26-week, multicenter, observational study conducted in Austrian diabetes centers and office-based practices to evaluate efficacy and safety of lixisenatide under real-life conditions in patients with type 2 diabetes. RESULTS: , disease duration 12.4 years), 113 completed the documentation at 6 months and 42% received basal insulin with or without oral antidiabetic drugs. The HbA1c declined from 8.7% (72 mmol/mol) to 7.9% (63 mmol/mol) and at study end 24.8% of the patients reached an HbA1c level below 7%. Fasting and postprandial glucose after lixisenatide administration were reduced by 27 ± 58 mg/dl and 45 ± 67 mg/dl, respectively. At study end body weight (- 4.5 ± 5.4 kg), triglycerides (- 10.8 ± 105 mg/dl), systolic blood pressure (- 4.8 ± 17.1 mmHg), and LDL cholesterol (- 3.7 ± 25 mg/dl) were reduced. The most commonly reported adverse events were gastrointestinal disorders (18.8%). Forty-three patients (30%) discontinued prematurely, mostly caused by lack of efficacy, occurrence of gastrointestinal disorders, and missing reimbursement. The average dose of insulin decreased slightly by 1.5 units (from 29.4 to 27.9). CONCLUSION: Lixisenatide demonstrated a similar efficacy and safety profile under real-life conditions as previously shown in randomized clinical trials. FUNDING: sanofi-aventis GmbH Austria.

Abstract Background Worldwide 13 million babies born prematurely every year have increased susceptibility to infection and require adequate immunization. Hexavalent vaccines against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b are standard of care in pediatric vaccination and are particularly important for preterm infants. Hexyon® is registered in Europe since April 2013. Methods Considering birth data from official national databases and only countries with periods of exclusive use of Hexyon from 2013-19, we estimated the total number of preterm infants (&amp;lt;37weeks GA) vaccinated with Hexyon. Results Since registration, Hexyon has been used in 23 European countries and exclusively used in the following: Austria, Feb-2017 to present; Belgium, Jul-2014 (Flanders)/Sep-2015 (Overall) to present; Bulgaria, Nov-2014 to Dec-2016; Croatia, Jan-2016 to present; Denmark, Feb-2016 to Apr-2017; Italy, Apr-2016 to present, exclusivity based on Regions; Macedonia, Oct-2015 to present; Norway, Feb-2017 to present; Romania, Apr-2015 to Dec-2017. The estimated total number of preterm infants during these periods of exclusive use is 183 000. Assuming 90% vaccination coverage, ∼164 700 preterm infants received at least 1 dose of this vaccine. From the analysis of the post-marketing safety data available to date, no new risk has been identified in preterm infants. Conclusions Hexyon has become a standard for hexavalent immunization in infants, regardless of the gestational age at birth. More than 90 million doses have been administered worldwide, including the estimated 164 000 preterm infants in the 9 European countries considered here. The EU Marketing Authorization granted in 2013 with no contraindication for use in preterm infants, was renewed in 2018 and the black triangle was removed confirming that the safety of Hexyon is well established. The marketing authorization holder continues to support evidence generation for use in preterm infants. Key messages Hexyon/Hexacima/Hexaxim has become a standard for hexavalent immunization in infants including for preterm infants (&amp;lt;37weeks GA); around 164 000 preterm infants in 9 European countries received it. The safety of Hexyon/Hexacima/Hexaxim is well established, no new risk has been identified in preterm infants from the analysis of the post-marketing safety data available to date.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

A prospective, multicenter, open-label, noninterventional study assessed the efficacy, safety, tolerability, and patient satisfaction with teriflunomide therapy over a 24-month follow-up period under real-world conditions in Austria. An all-comer population aged ≥18 years was followed in clinic and office-based settings. The primary objective of the study was the annualized relapse rate after 12 and 24 months of teriflunomide treatment. Patient-reported outcomes included treatment satisfaction, health-related quality of life, and fatigue, and were assessed based on the Short Form Health-36, Fatigue Severity Scale, and Treatment Satisfaction Questionnaire for Medication (TSQM)-9 questionnaires. Thirty-one patients were included in the analysis, 23 of whom were still on treatment after 24 months. At 12 months (n = 24), the annualized relapse rate was 0.3 (SD, 0.8), which indicated a significant decrease compared to the annualized relapse rate of 1.0 (SD, 0.9) observed during the 12-month reference period prior to treatment initiation (p = 0.009). Similarly, after 24 months of follow-up (n = 23), the annualized relapse rate of 0.2 (SD, 0.8) was significantly lower than that during the last 24 months reference period prior to treatment initiation of 0.7 (SD, 0.8) (p = 0.0003). The Expanded Disability Status Scale score remained stable over 12 and 24 months. This also applied to patient-reported fatigue of the Fatigue Severity Scale, with a mean change of 0.1 (SD, 1.0). Patient treatment satisfaction as assessed by the TSQM-9 increased for all three domains (i.e., effectiveness, convenience, global satisfaction). This was confirmed by the physician and multiple sclerosis nurse ratings of patient treatment satisfaction and ease of use. Adverse events occurred in 38.7%, with hair thinning and diarrhea as the most common. This noninterventional study showed a sustained favorable benefit–risk ratio for this disease-modifying treatment with teriflunomide over 24 months in patients with relapsing–remitting multiple sclerosis. Patient-reported outcomes and ratings performed by physicians and nurses showed overall trends to improvement for patient treatment satisfaction with teriflunomide treatment and its ease of administration.

Abstract Introduction. In newly diagnosed multiple myeloma (NDMM) patients (pts) eligible for autologous stem-cell transplant (ASCT), the phase 3 GMMG-HD7 trial (NCT03617731) Part 1 demonstrated that isatuximab, lenalidomide, bortezomib and dexamethasone (Isa-RVd) induction significantly improved minimal residual disease negativity (MRD-) rates (odds ratio: 1.82; p&amp;lt;0.001) and prolonged progression-free survival (PFS) compared with RVd (hazard ratio, 0.70; p=0.0184), regardless of the maintenance therapy received post-ASCT. Consequently, the 2025 EHA-EMN guidelines recommended Isa-RVd as standard of care for induction in patients with NDMM eligible for ASCT. This analysis evaluated the effect of Isa-RVd vs RVd induction on patient-reported outcomes (PROs) and health-related quality of life (HRQoL) from first random assignment through post-ASCT. Methods. Patient-reported outcomes (PROs) were recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30), the EORTC QLQ Multiple Myeloma Module 20-item (MY20), and the EuroQol 5-dimensional (EQ-5D-5L) visual analog scale (VAS) at baseline (BL), after induction, 60-90 days post-ASCT, and at the end of treatment (EOT). Prespecified analyses were conducted in the intent-to-treat population. Mixed model repeated measures (MMRM) analyzed the mean change from BL to post-ASCT. Time to first deterioration (TTFD) and time to first improvement (TTFI) were assessed using Kaplan-Meier methods and Cox proportional hazard models. Results. A total of 662 patients were randomized to Isa-RVd (n=331) or RVd (n=329) induction, followed by single or tandem ASCT and second randomization to maintenance with Isa-lenalidomide or lenalidomide alone. PRO completion rates were high across time points in both arms (≥90% at BL, ≥87% after induction, and ≥92% 60-90 days post-ASCT). At BL, patients in both arms reported similar functioning and symptom burden, QLQ-C30 Global Health Status (GHS/QoL), and EQ-5D-5L VAS. Pts on Isa-RVd reported a statistically significant reduction in fatigue vs RVd (overall mean [95% CI] difference in LS mean change from BL: -4.02 [-7.68, -0.37]; p=0.0312). Median TTFD in fatigue was longer in the Isa-RVd arm vs RVd (8.48 mo vs 5.22 mo; HR=0.78; p=0.0340), while median TTFI was shorter for Isa-RVd vs RVd (8.84 mo vs 10.05 mo; HR=1.26; p=0.0611). Clinically meaningful reduction in pain occurred in both arms, with Isa-RVd showing a numerically greater reduction vs RVd (overall mean [95% CI] difference in LS mean change from BL: -3.39 [-7.43, 0.64]; p=0.0991). Median TTFD in pain was 12.62 mo for Isa-RVd vs. 12.16 mo for RVd (HR=0.83; p=0.2336), while median TTFI was 5.06 mo for Isa-RVd vs 5.26 mo for RVd (HR=1.18; p=0.1393). No clinically meaningful deterioration in other symptom scales were observed in either arm. Both Isa-RVd and RVd showed a small improvement in physical functioning (LS mean change [SE] from BL: 4.95 [2.00] vs 3.91 [2.00]; p=0.5189) and a clinically meaningful improvement in emotional functioning (LS mean change [SE]: 13.27 [1.97] vs 12.94 [1.97]; p=0.8380). No notable differences between arms were observed for the other functional scales. Both treatments showed clinically meaningful improvement in future perspective, as measured by MY20 after induction and post-ASCT. The overall difference between arms significantly favored Isa-RVd over RVd (overall mean [95% CI] difference in LS mean change from BL: +5.64 [2.15, 9.13], p=0.0016). Each arm demonstrated clinically meaningful improvement in QLQ-C30 GHS/QoL post-ASCT, with no statistically significant difference between Isa-RVd and RVd (LS mean change [SE]: 10.17 [1.82] vs 9.22 [1.81]; p=0.5197). Similarly, pts in both treatment arms experienced a clinically meaningful improvement in EQ-5D-5L VAS post-ASCT, with numerical trend in favor of Isa-RVd (overall mean [95% CI] difference in LS mean change from BL: +1.47 [-1.28, 4.21], p=0.2939). Conclusions. The addition of isatuximab to RVd significantly improves the likelihood of achieving MRD- and prolongs PFS in transplant-eligible NDMM pts. This enhanced efficacy is observed without compromising overall HRQoL, and importantly, is associated with significant improvement in fatigue and a favorable trend in pain reduction, compared to RVd alone. These findings underscore the favorable benefit-risk profile and value of Isa-RVd quadruplet for transplant eligible NDMM pts.

INTRODUCTION: Hands are a key vector for pathogen transmission in healthcare, making effective hand antisepsis crucial for infection prevention. According to the European standard EN 1500, the reference method for evaluating hand antiseptics, a minimum rub-in time of 30 s is required. However, observations show healthcare workers typically spend less time on hand antisepsis. METHOD: To assess the feasibility of a reduced rub-in time under standardized conditions, the German Association for Applied Hygiene conducted a multi-centre ring trial in 14 laboratories using a modified EN 1500 protocol (15 s, 3 mL of 60% v/v propan-2-ol). In a randomized crossover design, volunteers' hands were contaminated with Escherichia coli K12 and treated either with the reference (2 × 3 mL/2 × 30 s) or the test protocol (1 x 3 mL/15 s). Microbial reduction was measured and non-inferiority statistically analysed. RESULTS: reductions than the reference in 13 out of 14 laboratories but demonstrated consistent reproducibility and satisfactory interlaboratory performance. Challenges in completing the full rub-in technique within 15 s were reported, indicating the need for targeted training. CONCLUSION: These findings support the methodological feasibility of a shortened protocol and are consistent with evolving clinical guidelines advocating reduced rub-in times, as well as with real-world practice, where healthcare workers typically spend less than 30 s on hand antisepsis. Nonetheless, any revision of EN 1500 should proceed cautiously to ensure antimicrobial efficacy, emphasizing complete hand coverage and strict adherence to technique.