Sanofi (Spain)

BackgroundInfluenza is a seasonal infection with a huge impact on morbidity and mortality in older adults, for whom vaccination is recommended. New influenza vaccines for this population have been introduced in Spain in the past 5 years, and a number of cost-effectiveness analyses (CEA) have been published to aid healthcare decision-making. The objective of this study was to assess possible sources of uncertainty in the CEAs of influenza vaccines for the older adults in Spain.MethodsA systematic review was performed to identify Spanish CEAs published since 2016. Potential sources of structural, methodologic and parametric uncertainty in CEA results were systematically analysed using the TRansparent Uncertainty ASsessmenT (TRUST) Tool, quality assessment checklists, and the WHO guidance on economic evaluations of influenza vaccine strategies. The primary sources of efficacy/effectiveness were analysed in depth to ascertain whether they could support the conclusions of the respective CEAs.ResultsSeven CEAs were included. Overall, they were designed and performed in accordance with the applicable guidelines; however, some critical sources of uncertainty were detected, mainly: (1) the choice and use of efficacy/effectiveness data (real-world single season studies, meta-analyses including studies with high risk of bias and/or high heterogeneity with biased interpretation); (2) use of fewer than 5 seasons to estimate influenza burden; (3) generalized use of influenza-like illness data to estimate effectiveness and burden, among others.ConclusionsSeemingly well-designed studies may conceal important sources of uncertainty that affect the results. This must be taken into account when interpreting results to support decision-making.

BackgroundAlemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Its efficacy and safety have been widely demonstrated in clinical trials, but experience from real-world cohorts is also needed to support its clinical use. Quality of life (QoL) outcomes are an important complement to the clinical benefits of treatment, offering a patient-centered perspective on how the drug contributes to general well-being. In this line we aimed to evaluate the QoL of patients treated with alemtuzumab in clinical practice.MethodsThis prospective 3-year multicenter study was carried out in adult patients diagnosed with RRMS who had started alemtuzumab according to clinical practice within 8 weeks before inclusion. The primary endpoint was the change in QoL over three years of treatment with alemtuzumab using the 29-item Multiple Sclerosis Impact Scale (MSIS-29). Secondary endpoints included changes from baseline in the 21-item Modified Fatigue Impact Scale (MFIS-21), Beck Depression Inventory (BDI-II), Symbol Digit Modalities Test (SDMT, oral version) and Work Productivity. Disability worsening was also assessed based on the Expanded Disability Status Scale (EDSS), along with the annualized relapse rate (ARR) and radiological activity.ResultsA cohort of 165 patients was analyzed (mean age 38.6 years, mean disease duration 8.5 years, mean EDSS score 3.3). MSIS-29 physical domain scores decreased significantly from baseline by a mean of 7.2 ± 1.8 points at year 1, 6.4 ± 2.2 at year 2 and 5.6 ± 2.3 at year 3 (p < 0.05 in all cases). Similarly, MSIS-29 psychological domain scores decreased significantly by a mean of 7.9 ± 2.4 points at year 1, 12.8 ± 2.9 at year 2 and 13.2 ± 3.0 at year 3 (p < 0.05 in all cases). Significant reductions from baseline were also evidenced in MFIS-21 and BDI-II scores, while SDMT scores remained unchanged. During the 3 years on alemtuzumab, the ARR was 0.15, representing an 83% reduction from the 2 years before initiation. At 3 years, 81.5% of patients were free from radiological activity and 87% were free from disability worsening.ConclusionsThese results indicate early and substantial improvements in patients’ perception of their QoL and functioning with alemtuzumab that were sustained over three years.

IntroductionMucus hypersecretion resulting from type 2 cytokines (e.g., interleukin [IL]-13) drives intermittent airway obstruction and remodeling. Dupilumab blocks the shared receptor component for IL-4/IL-13, improved lung function, and reduces rates of severe exacerbations in patients (≥12 years) with moderate-to-severe asthma for up to 3 years, or for up to 2 years in children (6–11 years). The VESTIGE study (NCT04400318) assessed the dupilumab’s impact on mucus airway plugging, volume, inflammation, and related lung function changes in patients with asthma.MethodsPatients (aged 21–70 years) with uncontrolled moderate-to-severe asthma, elevated type 2 biomarkers (baseline blood eosinophils ≥300 cells/µL and fractional exhaled nitric oxide [FeNO] ≥25 ppb), pre-bronchodilator percent predicted forced expiratory volume in 1 second (pre-BD ppFEV1) ≤80%, with ≥1 exacerbation in the year prior, were randomized 2:1 to add-on dupilumab 300 mg (n=72) or matched placebo (n=37) every 2 weeks (q2w) for 24 weeks. A validated mucus scoring system was used to quantify the number of bronchopulmonary segments completely occluded with mucus, resulting in a mucus plug score [0–20]. Quantification of voxels per mucus plug, measured by computed tomography, determined mucus volume. We also assessed the proportion of patients achieving FeNO <25 ppb and the least squares (LS) mean change in pre-BD FEV1 at Week 24.ResultsAt Week 24, patients treated with dupilumab had reduced airway mucus scores (LS mean difference [standard error, SE] from baseline was −4.9 [0.8] points vs placebo; nominal P<0.001) and reduced airway mucus volumes (−0.107 [0.020] mL vs placebo; nominal P<0.001). Patients receiving dupilumab were 9.8 times more likely to achieve FeNO <25 ppb by Week 24 than those on placebo (P<0.001). In addition, an improvement in pre-BD FEV1 was observed at Week 24 (LS mean difference [SE] vs placebo: 0.38 [0.11] L; nominal P<0.001). Furthermore, improvements from baseline to Week 24 in pre-BD FEV1 were strongly associated with decreases in airway mucus scores in dupilumab-treated patients (Pearson’s correlation coefficient −0.618; P<0.0001) (table 1).ConclusionDupilumab treatment led to a significant reduction in mucus airway plugging and mucus volume, as well as reduction in airway inflammation, contributing to improvements in lung function. S95 Table 1Effect of dupilumab on mucus plugging and mucus volume, airway inflammation, and lung function

Abstract Children with atopic dermatitis (AD) are at risk for lower bone mineral density (BMD) and lower alkaline phosphatase (ALP) levels than healthy children. Low BMD and ALP in children could contribute to a higher lifetime prevalence of fractures, osteopenia and osteoporosis. Dupilumab is a fully humanized monoclonal anti-interleukin (IL)-4R antibody approved for the treatment of AD in children. The objective of this analysis is to report the impact of dupilumab treatment on markers of bone mineralization in children aged 6–12 years with moderate-to-severe AD vs. reference intervals (RIs). Analysis was performed retrospectively on sera from participants in LIBERTY AD PEDS, a phase III placebo-controlled trial of 16 weeks (NCT03345914) and LIBERTY AD PED-OLE (NCT02612454), an open-label extension trial in which eligible patients received dupilumab until week 52. Biomarkers, including bone ALP (BALP), procollagen type 1 N-terminal propeptide (P1NP), C-terminal crosslinking telopeptide of β-1 collagen (β-CTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1), were analysed at baseline, 8, 12 and 16 weeks; only BALP was measured at 52 weeks. Both dupilumab dosing regimens led to significant increases in geometric mean (SE) levels of BALP at 8, 12 and 16 weeks compared with placebo. For the 100/200-mg Q2W group, at week 8 the BALP level was 72.7 (1.03) μg L−1 vs. 62.0 (1.05) μg L−1 (P &amp;lt; 0.0001), at week 12 it was 74.7 (1.03) μg L−1 vs. 64.3 (1.05) μg L−1 (P &amp;lt; 0.001) and at week 16 it was 78.0 (1.03) μg L−1 vs. 65.0 (1.04) μg L−1 (P &amp;lt; 0.001). For the 300-mg Q4W group, at week 8 the BALP level was 76.7 (1.03) μg L−1 vs. 62.0 (1.05) μg L−1 (P &amp;lt; 0.001), at week 12 it was 73.3 (1.04) μg L−1 vs. 64.3 (1.05) μg L−1 (P = 0.002) and at week 16 it was 77.3 (1.03) μg L−1 vs. 65.0 (1.04) μg L−1 (P &amp;lt; 0.001). At 52 weeks, BALP levels were statistically significantly increased compared with baseline [placebo vs. placebo transitioned to dupilumab: 64.2 (1.04) μg L−1 vs. 82.9 (1.04) μg L−1 (P &amp;lt; 0.001); 100/200 mg Q2W: 62.0 (1.05) μg L−1 vs. 83.8 (1.03) μg L−1 (P &amp;lt; 0.001); 300 mg Q4W: 64.1 (1.04) μg L−1 vs. 78.7 (1.04) μg L−1 (P &amp;lt; 0.001)] and also increased within RIs. From baseline to week 16, OC, P1NP and β-CTX levels improved from below to within the RIs, and levels of IGF-1 increased from the lower limit of the RI. However, data points were limited due to insufficient sera volumes, preventing statistical analyses for these biomarkers. The overall results suggest an increase in bone mineralization biomarkers in paediatric patients with moderate-to-severe AD following dupilumab treatment. Funding sources:research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

<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.