Drugs
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The adhesive capsaicin dermal patch (Qutenza®) delivers a high concentration (8% w/w) of synthetic capsaicin, a highly selective agonist of transient receptor potential vanilloid-1 (TRPV-1), directly to the site of pain. The capsaicin 8% dermal patch is indicated in the EU for the treatment of peripheral neuropathic pain (PNP) in adults, either alone or in combination with other medicinal products for pain. In patients with painful diabetic peripheral neuropathy, a single 30-min application of the capsaicin 8% dermal patch provided 12 weeks of pain relief and improved sleep quality compared with placebo. ⋯ Results in patients with HIV-associated neuropathy were equivocal, with a significant improvement in pain intensity observed in one trial, but not in the other. The capsaicin 8% dermal patch was generally well tolerated; transient application-site reactions were the most common adverse events. In conclusion, the capsaicin 8% dermal patch is a useful addition to the treatment options currently available for patients with PNP.
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Ionis Pharmaceuticals and Akcea Therapeutics have developed inotersen (Tegsedi™), an antisense oligonucleotide inhibitor of mutant and wild-type human transthyretin (TTR), for the treatment of hereditary transthyretin amyloidosis (hATTR). Mutation of the TTR gene results in accumulation of TTR protein fragments as amyloid deposits throughout the organs in patients with hATTR, including the peripheral nervous system and the heart. ⋯ Based on these results, inotersen was recently approved in the EU for the treatment of stage 1 or 2 polyneuropathy in adult patients with hATTR and is under evaluation in the USA and Canada for a similar indication. This article summarizes the milestones in the development of inotersen leading to this first approval.
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Intravenous elotuzumab (Empliciti™), a monoclonal antibody targeting the signalling lymphocytic activation molecule F7 (SLAMF7) glycoprotein, is approved for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in previously-treated adult patients. In the pivotal, multinational, phase III ELOQUENT-2 trial in adults with relapsed and/or refractory multiple myeloma, elotuzumab in combination with lenalidomide and dexamethasone significantly prolonged median progression-free survival (PFS) and increased overall response rate (ORR; co-primary endpoints) compared with lenalidomide and dexamethasone alone. ⋯ Elotuzumab combination therapy had a generally manageable tolerability profile and the most common adverse events (AEs) of grade ≥ 3 severity were haematological (e.g. lymphocytopenia, anaemia, thrombocytopenia, neutropenia). Elotuzumab plus lenalidomide and dexamethasone extends the treatment options available for the management of relapsed and/or refractory multiple myeloma.
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Immune modulatory treatment regimens, led by immune checkpoint inhibitors, have transformed the treatment of clear-cell renal cell carcinoma. First-in-class, the PD-1 inhibitor nivolumab improved overall survival in advanced renal cell carcinoma following prior anti-angiogenic therapy, an important shift in the management of clear-cell renal cell carcinoma. Further improvements of long-term outcomes will be driven by combinations in the first-line setting, including PD-1/PD-L1 associated with antiangiogenic therapies, or PD1/PD-L1 inhibitors with other immune checkpoint inhibitors such as anti-CTLA-4, anti-LAG-3 or TIM-3 targeted therapies. ⋯ Clinical trials of immune checkpoint inhibitors are also actively investigated in the localized adjuvant or neoadjuvant setting. Nevertheless, the search for biomarkers along with new clinical trial designs will be crucial to better select the patients that may derive the greatest benefit from these advances. The continuing improvement of antitumor immunity comprehension and the emergence of new immune modulatory treatments will deeply change the management of renal cell carcinoma for the years to come.
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Focal-onset seizures are among the most common forms of seizures in children and adolescents and can be caused by a wide diversity of acquired or genetic etiologies. Despite the increasing array of antiseizure drugs available, treatment of focal-onset seizures in this population remains problematic, with as many as one-third of children having seizures refractory to medications. ⋯ As antiseizure drug efficacy is comparable in children and adults, here we focus on pharmacokinetic aspects, drug-drug interactions, and side effect profiles. Finally, we provide some suggestions for choosing the optimal medication for the appropriate patient.