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Questions of mutual covering and equivalence of cones of monotone functions and the corresponding estimates of their majorants are studied. Two types of coverings are considered: pointwise and integral. They correspond to pointwise and integral estimates of the majorants on these cones. The results obtained are used to derive formulas that allow estimating pointwise and integral majorants of decreasing rearrangements for generalized Riesz and Bessel potentials., Author(s): E. G. Bakhtigareeva [sup.1], M. L. Goldman [sup.1], G. Zh. Karshygina [sup.2] Author Affiliations: (1) https://ror.org/03zeg8w71, grid.426543.2, 0000 0004 0619 9030, Department of Function Theory, Steklov Mathematical Institute of [...]

Author(s): M. L. Goldman [sup.1], G. Zh. Karshygina [sup.2] Author Affiliations: (1) Moscow, Russia (2) Karaganda, Kazakhstan Introduction The paper studies the issues of mutual covering and equivalence for cones [...]

Pamela L Zeitlin,1 Mila Leong,2 Jeremy Cole,3 Raburn M Mallory,4 Vivian H Shih,5 Richard F Olsson,6 Mitchell Goldman5 On behalf of the ALIZE study investigators 1Department of Pediatrics, National Jewish Health, Denver, CO, USA; 2Pediatric Pulmonary and Asthma Associates, Northfield, NJ, USA; 3OK Clinical Research, LLC, Edmond, OK, USA; 4MedImmune LLC, Gaithersburg, MD, USA; 5AstraZeneca, Gaithersburg, MD, USA; 6AstraZeneca, Gothenburg, Sweden Background and objectives: Benralizumab is a humanized, afucosylated monoclonal antibody against the IL-5Rα. Initial monthly followed by every-other-month injections result in rapid and nearly complete eosinophil depletion. We evaluated whether three doses of benralizumab modifies antibody response to seasonal influenza vaccination for adolescent/young adult patients with moderate to severe asthma.Methods: ALIZE (NCT02814643) was a Phase IIIb randomized controlled trial of patients aged 12–21 years receiving medium- to high-dosage inhaled corticosteroids/long-acting β2-agonists. Patients received benralizumab 30 mg or placebo at Weeks 0, 4, and 8, plus tetravalent influenza vaccination at Week 8. At Week 12, strain-specific antibody responses following vaccination were assessed for four influenza antigens by hemagglutination inhibition (HAI) and microneutralization (MN) assays.Results: A total of 103 patients were randomized and received benralizumab (n=51) or placebo (n=52). There were no consistent differences in HAI or MN antibody responses at Week 12 between patients receiving benralizumab or placebo. HAI geometric mean fold rises (GMFRs) for all influenza strains tested were 3.3–4.2 for benralizumab vs 3.4–3.9 for placebo; MN GMFRs were 2.8–5.1 for benralizumab vs 3.2–4.4 for placebo. A ≥4-fold rise in HAI from Weeks 8 to 12 occurred in 44.0%–56.0% and 30.6%–49.0% of patients receiving benralizumab and placebo, respectively. At Week 12, 78.0%–100% vs 79.6%–100% of patients receiving benralizumab and placebo, respectively, achieved a ≥40 HAI antibody titer. There were no significant safety findings.Conclusion: Benralizumab did not impair the antibody response to seasonal virus vaccination in adolescents and young adult patients with moderate to severe asthma. Keywords: benralizumab, interleukin-5, interleukin-5 receptor, influenza vaccination, eosinophils, antibody response, asthma

Gary T Ferguson,1 Adel H Mansur,2 Joshua S Jacobs,3 Jacques Hebert,4 Corbin Clawson,5 Wenli Tao,6 Yanping Wu,6 Mitchell Goldman6 On behalf of the GREGALE study investigators 1Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 2Department of Respiratory Medicine, Birmingham Heartlands Hospital, University of Birmingham, Birmingham, UK; 3Allergy & Asthma Clinical Research, Walnut Creek, CA, USA; 4Clinique Spécialisée en Allergie de la Capitale, Allergie et Immunologie, CHU de Québec, Québec, QC, Canada; 5MedImmune LLC, Gaithersburg, MD, USA; 6AstraZeneca, Gaithersburg, MD, USA Background: Patients prefer at-home subcutaneous administration of biologics across different diseases, yet no biologic is approved for at-home use for severe, uncontrolled asthma. Objective: We assessed at-home functionality, reliability, and performance of an accessorized pre-filled syringe (APFS) for subcutaneous benralizumab administration, an anti-eosinophil monoclonal antibody indicated for add-on maintenance treatment of patients with severe eosinophilic asthma. Materials and methods: Patients (N=116) with severe, uncontrolled asthma despite receiving medium- or high-dosage inhaled corticosteroids and long-acting β2-agonists received up to 5 APFS-administered subcutaneous doses (Weeks 0, 4, 8, 12, and 16) of benralizumab 30 mg. The first 3 doses were administered at the study sites. The patient/caregiver administered the last 2 doses at home. Endpoints included the percentage of dispensed APFS that were used successfully blood eosinophil counts, Asthma Control Questionnaire 6, and safety. Results: Nearly all dispensed APFS were successfully used in the clinic and at home (Week 0: 116/116, 100%; Week 4: 116/117, 99%; Week 8: 115/115, 100%; Week 12: 112/114, 98%; Week 16: 108/109, 99%). Only 1 APFS malfunctioned out of 573 dispensed. Two at-home administrations were unsuccessful because of patient-use error. One unreturned APFS was recorded as nonfunctional. Mean Asthma Control Questionnaire 6 scores decreased from baseline through all post-baseline time points, and nearly complete depletion of eosinophils was observed at the end of treatment. The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and sinusitis. Five patients (4%) experienced transient mild or moderate injection-site reactions. Conclusion: The APFS was functional, reliable, and performed equally well in the clinic and at home. Keywords: biologic, subcutaneous, eosinophil, asthma, treatment, patient preference

Coccidioidomycosis is a common cause of community acquired pneumonia in Arizona. Although self-limited in the majority of patients, immunosuppression often causes a blunting of symptoms and a poor antibody response. We present a patient with coccidioidomycosis while receiving adalimumab for psoriasis. The diagnosis was challenging due to negative serology and constellation of symptoms on immunosuppression.