Background: Severe asthma is a heterogeneous inflammatory disease driven by eosinophilic inflammation in the majority of cases. Despite biologic therapy patients may still be sub-optimally controlled, and the choice of the best biologic is a matter of debate. Indeed, switching between biologics is common, but no official guidelines are available and real-world data are limited.
Materials And Methods: In this analysis of the Italian, multi-center, observational, retrospective study, ANANKE. Patients with severe eosinophilic asthma treated with benralizumab were divided in two groups based on history of previous biologic therapy (biologic-experienced [suboptimal response] vs naïve). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment. Change over time in blood eosinophils, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use following benralizumab initiation were collected in the two groups.
Results: A total of 147 biologic-naïve and 58 biologic-experienced (34 omalizumab, 19 mepolizumab, and 5 omalizumab-mepolizumab) patients were enrolled. Biologic-experienced patients were more likely to be atopic and have a higher AER despite more frequent OCS use. Similar reductions in AER (>90% in both groups), OCS use (≥49% reduction in dosage and ≥41% able to eliminate OCS), ACT improvement (≥7 points gained in 48 weeks) and lung function (≥300 mL of FEV improvement in 48 weeks) were observed after benralizumab introduction within the two groups. There were no registered discontinuations of benralizumab for safety reasons.
Conclusion: In this analysis, patients who were switched to benralizumab because of suboptimal control with a previous biologic therapy were more likely to be atopic and more often treated with omalizumab. Benralizumab is effective in both naïve patients and those previously treated with a biologic.
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http://dx.doi.org/10.3389/fmed.2022.950883 | DOI Listing |
J Antimicrob Chemother
January 2025
Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana.
Objectives: We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.
Methods: The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana's national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200-999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL).
Front Med (Lausanne)
December 2024
Rheumatology Unit, Department of Medicine-DIMED, University - Padova University Hospital, Padua, Italy.
Objectives: This pilot study aimed to identify early predictors of drug retention in patients with clinically active peripheral psoriatic arthritis who initiated or switched to therapy with biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs).
Methods: Clinical and ultrasound assessments were conducted at baseline (t0) and subsequently at 1 (t1), 3 (t3), and 6 (t6) months. Ultrasound evaluations targeted joints/entheses according to PsASon-Score13 and the most clinically involved joint/enthesis/tendon or the two most clinically involved joints/entheses/tendons (MIJET and 2MIJET).
Metabol Open
December 2024
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, Greece.
EXCLI J
November 2024
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy.
The p53-MDM2 pathway plays a crucial role regulating tumor suppression and is a focal point of cancer research. This literature review delves into the complex interplay between the tumor suppressor protein p53 and its main regulator MDM2, highlighting their interaction and implications in cancer development and progression. The review compiles and summarizes the existing understanding of the biology and regulation of p53 and MDM2, emphasizing their roles in various cellular processes, including cell cycle regulation, DNA repair, apoptosis, and metabolism.
View Article and Find Full Text PDFRSC Adv
January 2025
Department of Chemistry, College of Science, King Saud University P. O. Box 2455 Riyadh 11451 Saudi Arabia
The search for effective anti-cancer therapies has led to the exploration of dual inhibition strategies targeting multiple key molecular pathways. In this study, we aimed to design a novel candidate capable of dual inhibition targeting both EGFR (Epidermal Growth Factor Receptor) and PARP-1 (poly(ADP-ribose)polymerase-1), two crucial proteins implicated in cancer progression and resistance mechanisms. Through molecular hybridization and structure-based drug design approaches, we synthesized a series of compounds based on spirooxindole with triazole scaffolds with the potential for dual EGFR and PARP-1 inhibition.
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