Sustained Improvement in Clinical Efficacy, Asthma Control, and Quality of Life in Patients With Severe, Oral Corticosteroid (OCS)-Dependent Asthma Treated With Dupilumab : LIBERTY ASTHMA TRAVERSE Study

Acknowledgments and funding sources Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02528214 (VENTURE)/NCT02134028 (TRAVERSE). Medical writing/editorial assistance was provided by Nevena Krstić, PhD, of Excerpta Medica, and was funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline.Peer reviewedPostprin

Persistent Reductions in OCS Use in Patients With Severe, OCS-Dependent Asthma Treated With Dupilumab : LIBERTY ASTHMA TRAVERSE Study

Acknowledgments and funding sources Data first presented at the 118th International Conference of the American Thoracic Society (ATS 2022); San Francisco, CA, USA; May 13–18, 2022. Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02528214 (VENTURE)/NCT02134028 (TRAVERSE). Medical writing/editorial assistance was provided by Anthony Aggidis, PhD, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. Alternate presenters: Anne Atenhan and Mayank Thakur.Peer reviewe

Dupilumab reduces OCS use and improves lung function in patients with severe OCS-dependent asthma

Peer reviewedPostprin

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

FUNDING Regeneron Pharmaceuticals NCT0213402; NCT02528214 Sanofi NCT0213402; NCT02528214Peer reviewedPublisher PD

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. This post hoc analysis assesses the impact of OCS dose at baseline (≤10 o

Use of Quantitative Pharmacology in the Development of HAE1, a High-Affinity Anti-IgE Monoclonal Antibody

HAE1, a high-affinity anti-IgE monoclonal antibody, is discussed here as a case study in the use of quantitative pharmacology in the development of a second-generation molecule. In vitro, preclinical, and clinical data from the first-generation molecule, omalizumab, were heavily leveraged in the HAE1 program. A preliminary mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for HAE1 was developed using an existing model for omalizumab, together with in vitro binding data for HAE1 and omalizumab. When phase I data were available, the model was refined by simultaneously modeling PK/PD data from omalizumab studies with the available HAE1 phase I data. The HAE1 clinical program was based on knowledge of the quantitative relationship between a pharmacodynamic biomarker, suppression of free IgE, and clinical response (e.g., lower exacerbation rates) obtained in pivotal studies with omalizumab. A clinical trial simulation platform was developed to predict free IgE levels and clinical responses following attainment of a target free IgE level (≤10 IU/ml). The simulation platform enabled selection of four doses for the phase II dose-ranging trial by two independent methods: dose-response non-linear fitting and linear mixed modeling. Agreement between the two methods provided confidence in the doses selected. Modeling and simulation played a large role in supporting acceleration of the HAE1 program by enabling data-driven decision-making, often based on confirmation of projections and/or learning from incoming new data

Community perceptions of malaria and vaccines in the South Coast and Busia regions of Kenya

<p>Abstract</p> <p>Background</p> <p>Malaria is a leading cause of morbidity and mortality in children younger than 5 years in Kenya. Within the context of planning for a vaccine to be used alongside existing malaria control methods, this study explores sociocultural and health communications issues among individuals who are responsible for or influence decisions on childhood vaccination at the community level.</p> <p>Methods</p> <p>This qualitative study was conducted in two malaria-endemic regions of Kenya--South Coast and Busia. Participant selection was purposive and criterion based. A total of 20 focus group discussions, 22 in-depth interviews, and 18 exit interviews were conducted.</p> <p>Results</p> <p>Participants understand that malaria is a serious problem that no single tool can defeat. Communities would welcome a malaria vaccine, although they would have questions and concerns about the intervention. While support for local child immunization programs exists, limited understanding about vaccines and what they do is evident among younger and older people, particularly men. Even as health care providers are frustrated when parents do not have their children vaccinated, some parents have concerns about access to and the quality of vaccination services. Some women, including older mothers and those less economically privileged, see themselves as the focus of health workers' negative comments associated with either their parenting choices or their children's appearance. In general, parents and caregivers weigh several factors--such as personal opportunity costs, resource constraints, and perceived benefits--when deciding whether or not to have their children vaccinated, and the decision often is influenced by a network of people, including community leaders and health workers.</p> <p>Conclusions</p> <p>The study raises issues that should inform a communications strategy and guide policy decisions within Kenya on eventual malaria vaccine introduction. Unlike the current practice, where health education on child welfare and immunization focuses on women, the communications strategy should equally target men and women in ways that are appropriate for each gender. It should involve influential community members and provide needed information and reassurances about immunization. Efforts also should be made to address concerns about the quality of immunization services--including health workers' interpersonal communication skills.</p

Performance of a malaria microscopy image analysis slide reading device.

BACKGROUND: Viewing Plasmodium in Romanovsky-stained blood has long been considered the gold standard for diagnosis and a cornerstone in management of the disease. This method however, requires a subjective evaluation by trained, experienced diagnosticians and establishing proficiency of diagnosis is fraught with many challenges. Reported here is an evaluation of a diagnostic system (a "device" consisting of a microscope, a scanner, and a computer algorithm) that evaluates scanned images of standard Giemsa-stained slides and reports species and parasitaemia. METHODS: The device was challenged with two independent tests: a 55 slide, expert slide reading test the composition of which has been published by the World Health Organization ("WHO55" test), and a second test in which slides were made from a sample of consenting subjects participating in a malaria incidence survey conducted in Equatorial Guinea (EGMIS test). These subjects' blood was tested by malaria RDT as well as having the blood smear diagnosis unequivocally determined by a worldwide panel of a minimum of six reference microscopists. Only slides with unequivocal microscopic diagnoses were used for the device challenge, n = 119. RESULTS: On the WHO55 test, the device scored a "Level 4" using the WHO published grading scheme. Broken down by more traditional analysis parameters this result was translated to 89% and 70% sensitivity and specificity, respectively. Species were correctly identified in 61% of the slides and the quantification of parasites fell within acceptable range of the validated parasitaemia in 10% of the cases. On the EGMIS test it scored 100% and 94% sensitivity/specificity, with 64% of the species correct and 45% of the parasitaemia within an acceptable range. A pooled analysis of the 174 slides used for both tests resulted in an overall 92% sensitivity and 90% specificity with 61% species and 19% quantifications correct. CONCLUSIONS: In its current manifestation, the device performs at a level comparable to that of many human slide readers. Because its use requires minimal additional equipment and it uses standard stained slides as starting material, its widespread adoption may eliminate the current uncertainty about the quality of microscopic diagnoses worldwide

Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL-4) and IL-13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS-24/SINUS-52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery. Methods Patients were randomized to placebo or dupilumab 300 mg every 2 weeks. Post hoc subgroup analyses were performed for patients with 0, >= 1, 1/2, or >= 3 prior surgeries, and for patients who had surgery within = 10 years. Efficacy outcomes at 24 weeks included co-primary endpoints nasal polyp score (NPS) and nasal congestion (NC), and Lund-Mackay (LMK), 22-item Sino-Nasal Outcome Test (SNOT-22), and smell scores. Results Of 724 patients randomized, 459 (63.4%) had >= 1 prior surgery. Baseline sinus disease (NPS, NC, LMK) and olfactory dysfunction (University of Pennsylvania Smell Identification Test [UPSIT] and loss of smell) scores were worse for patients with >= 3 prior surgeries vs no surgery. Baseline NPS and LMK were worse in patients with Dupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery