Drugs
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Dupilumab (Dupixent®) is a fully human monoclonal antibody against the interleukin (IL)-4 receptor α subunit of IL-4 and IL-4/IL-13 receptor complexes. IL-4 and IL-13 are key cytokines in driving type 2 inflammation, a dominant and largely eosinophilic inflammatory pathway in asthma. ⋯ Dupilumab displayed efficacy across various patient subgroups, although those with heightened type 2 immune activity, including elevated eosinophils and fractional exhaled nitric oxide, tended to have a more prominent treatment benefit. Dupilumab is consequently widely indicated (and a valuable treatment option) as an add-on therapy in patients aged ≥ 12 years who have severe/moderate-to-severe asthma with a type 2 inflammation/eosinophilic phenotype despite conventional treatments or have OCS-dependent asthma.
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For the last three decades, the guidelines for asthma management have supported a stepwise therapeutic approach, based on the administration of controller medications (especially inhaled corticosteroids) complemented by on-demand use of rescue medication. Classically, the rescue medication recommended comprised short-acting β agonists (SABA). Some years ago, the use of Symbicort Maintenance and Reliever Therapy (SMART) demonstrated the benefits of a combination of budesonide-formoterol, an inhaled corticosteroid, and a long-acting β agonist (ICS-LABA) as rescue medication in moderate and severe asthma. ⋯ For step 1, symptom-driven or as-needed treatment with ICS-LABA is recommended rather than SABA alone (the preferred option until the last GINA update). Finally, the SIENA study showed that 73% of patients with mild asthma do not have an eosinophilic phenotype and that these patients have a similar clinical response to ICS (mometasone) and antimuscarinic drugs (tiotropium), results that challenge the indication of a drug combination that incorporates ICS as a first option. Overall, we believe there is insufficient evidence for the systematic recommendation of as-needed ICS-LABA instead of SABA on request for GINA step 1 or as a replacement for chronic ICS in GINA step 2.
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Upadacitinib (Rinvoq™), an orally-administered Janus kinase 1 (JAK-1) inhibitor, is being developed by AbbVie for the treatment of rheumatoid arthritis. In August 2019, based on positive results from multinational phase III trials conducted in patients with rheumatoid arthritis, upadacitinib received marketing approval in the USA for the treatment of moderately to severely active rheumatoid arthritis and an inadequate response or intolerance to methotrexate. This article summarizes the milestones in the development of upadacitinib leading to this first approval for the treatment of rheumatoid arthritis.
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Review
Leave it to Lefamulin: A Pleuromutilin Treatment Option in Community-Acquired Bacterial Pneumonia.
Lefamulin (BC-3781) is the first systemic pleuromutilin antibiotic found to be safe and effective in the treatment of community-acquired bacterial pneumonia (CABP) in humans. This novel antibiotic was developed to combat the increasing incidence of bacterial resistance to current therapies. As the first semisynthetic pleuromutilin for systemic use in humans, lefamulin has demonstrated efficacy against the most common bacteria responsible for CABP, including strains exhibiting resistance to macrolides, fluoroquinolones, tetracyclines, vancomycin, and beta-lactams. ⋯ Two phase III trials (LEAP-1 and LEAP-2) have demonstrated similar findings, meeting non-inferiority criteria for CABP with a minimal side-effect profile. Pharmacokinetic and pharmacodynamic evaluations have shown sufficient drug levels in plasma, subcutaneous adipose tissue, skeletal muscle, and epithelial lining fluid, warranting further investigation for other clinical uses. Lefamulin was approved by the United States Food and Drug Administration (FDA) on 19 August 2019 for the treatment of CABP.