Drugs
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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.
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Review
Current and Innovative Pharmacological Options to Treat Typical and Atypical Trigeminal Neuralgia.
Trigeminal neuralgia is a representative neuropathic facial pain condition, characterised by unilateral paroxysmal pain in the distribution territory of one or more divisions of the trigeminal nerve, triggered by innocuous stimuli. A subgroup of patients with trigeminal neuralgia [TN (previously defined as atypical TN)] also suffer from concomitant continuous pain, i.e. a background pain between the paroxysmal attacks. The aim of this review is to provide current, evidence-based, knowledge about the pharmacological treatment of typical and atypical TN, with a specific focus on drugs in development. ⋯ Although carbamazepine and oxcarbazepine are effective in virtually the totality of patients, they are responsible for side effects causing withdrawal from treatment in an important percentage of cases. A new, better tolerated, Nav1.7 selective state-dependent, sodium channel blocker (vixotrigine) is under development. Future trials testing the effect of combination therapy in patients with TN are needed, especially in patients with concomitant continuous pain and in TN secondary to multiple sclerosis.
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The article Andexanet Alfa: First Global Approval, written by Young-A Heo, was originally published Online First without open access.
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Intravenous andexanet alfa [coagulation factor Xa (recombinant), inactivated-zhzo; Andexxa®] is a first-in-class recombinant modified factor Xa protein that has been developed by Portola Pharmaceuticals as a universal antidote to reverse anticoagulant effects of direct or indirect factor Xa inhibitors. In May 2018, andexanet alfa received its first global approval in the USA for use in patients treated with rivaroxaban and apixaban, when reversal of anticoagulant effects is required in life-threatening or uncontrolled bleeding. Intravenous andexanet alfa is under regulatory review in the EU and is undergoing clinical development in Japan. This article summarizes the milestones in the development of andexanet alfa leading to this first global approval for reversing anticoagulation of rivaroxaban and apixaban in adults.