Drugs
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Intravenous daratumumab (DARZALEX®) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease. ⋯ Infusion-related reactions (IRRs) were the most common adverse events; these were predominantly grade 1 or 2 and mostly occurred during the first infusion. The most common grade 3-4 adverse events associated with daratumumab triple combination therapy were thrombocytopenia, neutropenia and anaemia. Although final OS data are awaited, current evidence indicates that daratumumab is a valuable addition to the treatment options currently available for patients with relapsed or refractory multiple myeloma.
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No specific antivirals are currently available for two emerging infectious diseases, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). A literature search was performed covering pathogenesis, clinical features and therapeutics, clinically developed drugs for repurposing and novel drug targets. This review presents current knowledge on the epidemiology, pathogenesis and clinical features of the SARS and MERS coronaviruses. ⋯ However, the information in this review is not meant to guide clinical decisions, and any therapeutic described here should only be used in context of a clinical trial. Potential targets for novel antivirals and antibodies are discussed as well as lessons learned from treatment development for other RNA viruses. The article concludes with a discussion of the gaps in our knowledge and areas for future research on emerging coronaviruses.
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Tofacitinib (Xeljanz®) is a potent, selective JAK inhibitor that preferentially inhibits Janus kinase (JAK) 1 and JAK3. In the EU, oral tofacitinib 5 mg twice daily is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant of, one or more DMARDs. Several clinical studies of ≤ 24 months' duration showed that tofacitinib monotherapy (as first- or second-line treatment) and combination therapy with a conventional synthetic DMARD (csDMARD; as second- or third-line treatment) was effective in reducing signs and symptoms of disease and improving health-related quality of life (HR-QOL), with benefits sustained during long-term therapy (≤ 96 months). ⋯ However, the incidence of herpes zoster (HZ) was higher with tofacitinib than in the general RA population, although infections were clinically manageable. When added to background methotrexate, tofacitinib was noninferior to adalimumab in terms of efficacy, and both combination therapies had generally similar tolerability profiles. Although additional comparative studies are needed to more definitively position tofacitinib relative to bDMARDs and other targeted synthetic DMARDs, current evidence indicates that oral tofacitinib is a useful option for the treatment of patients with RA.
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Enasidenib (Idhifa®) is an oral isocitrate dehydrogenase-2 (IDH2) inhibitor developed by Celgene Corporation under a global, exclusive license from Agios Pharmaceuticals. Enasidenib has been approved in the USA for the treatment of adults with relapsed or refractory acute myeloid leukaemia (AML) and an IDH2 mutation as detected by an FDA-approved test. It is at various stages of development in other countries for AML, myelodysplastic syndromes and solid tumours. This article summarizes the milestones in the development of enasidenib leading to this first global approval in the USA for the treatment of adults with relapsed or refractory IDH2-mutated AML.
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Delirium is a neurocognitive syndrome arising from acute global brain dysfunction, and is prevalent in up to 42% of patients admitted to palliative care inpatient units. The symptoms of delirium and its associated communicative impediment invariably generate high levels of patient and family distress. Furthermore, delirium is associated with significant patient morbidity and increased mortality in many patient populations, especially palliative care where refractory delirium is common in the dying phase. ⋯ Non-pharmacological strategies for the management of delirium play a fundamental role and should be optimized through the collective efforts of the whole interprofessional team. Refractory agitated delirium in the last days or weeks of life may require the use of pharmacological sedation to ameliorate the distress of patients, which is invariably juxtaposed with increasing distress of family members. Further evaluation of multicomponent strategies for delirium prevention and treatment in the palliative care patient population is urgently required.