Expert review of clinical pharmacology
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Expert Rev Clin Pharmacol · Aug 2016
Review Comparative StudyCanakinumab for the treatment of active systemic juvenile idiopathic arthritis.
Canakinumab, a fully human monoclonal antibody against interleukin-1β, is a relatively new medication approved for treatment of systemic juvenile idiopathic arthritis (SJIA). Here, we review data supporting use of canakinumab for patients with active SJIA, as compared to other available biologic medications. ⋯ This article provides an overview of chemistry of canakinumab as well as the phase II and phase III trials that led to approval for treatment of active SJIA. To undertake this review, the authors performed literature search using Pubmed, with keywords 'canakinumab,' 'biologic,' 'anti-IL-1B,' and 'systemic juvenile idiopathic arthritis,' focusing on publications within the last 5 years. Expert commentary: Canakinumab has shown efficacy in treatment of SJIA with active systemic features including fever. There is no evidence to suggest increased risk of macrophage activation syndrome. Its use in the treatment of chronic arthritis without active systemic features has not been approved and warrants further study.
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Expert Rev Clin Pharmacol · Aug 2016
Review Comparative StudyAlectinib for ALK-positive non-small-cell lung cancer.
Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5% of advanced non-small-cell lung cancer (NSCLC) patients. Despite the initial response, after a median of 1-2 years, ALK-positive patients developed an acquired resistance to the ALK-inhibitor crizotinib. Among the most promising second-generation ALK-inhibitors, alectinib is being investigated in crizotinib-naïve and -resistant ALK-positive NSCLC patients. ⋯ The current state-of-the-art of ALK-inhibitors treatment, and in particular the role of alectinib in this setting, is reviewed and discussed. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken. Expert commentary: Alectinib reports promising results with a good safety profile, becoming a potentially very important option for ALK-translocated NSCLC patients. The preliminary results from the J-ALEX phase III randomized trial performed in ALK-rearranged NSCLC Japanese patients showed a better activity and tolerability of alectinib versus crizotinib.
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Expert Rev Clin Pharmacol · Aug 2016
ReviewBedaquiline as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis.
Few innovative anti-microbial products have been brought to market in recent years to combat the global multidrug resistant-tuberculosis (MDR-TB) epidemic. Bedaquiline, a novel oral diarylquinoline, was approved by the US FDA as a part of combination therapy in adults with pulmonary MDR-TB based on phase II trials. ⋯ Pubmed searches were conducted using search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included World Health Organization, Clinicaltrial.gov, US Food and Drug Administration. Bedaquiline is an ATP synthase inhibitor specific for M. tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4 and it's drug exposure can be influenced by inducers and inhibitors of this enzyme. Phase II studies showed promising results on efficacy of bedaquiline when being used in combination with a background regimen for MDR-TB. Main safety concerns include QTc prolongation and hepatotoxicity. Phase III trials are ongoing to confirm efficacy findings from phase II studies and provide additional evidence of safety and efficacy. Expert commentary: Critical data for long-term efficacy and safety are incomplete and scarce, supporting the cautious use of bedaquiline.