Drugs
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Ustekinumab (Stelara(®)) has been recently approved in the EU and the USA as intravenous induction and subcutaneous maintenance therapy for adult patients with moderately to severely active Crohn's disease who have failed or were intolerant to treatment with immunomodulators, corticosteroids or at least one tumour necrosis factor (TNF) antagonist. Ustekinumab, a monoclonal antibody to the shared p40 subunit of the proinflammatory interleukin (IL)-12 and IL-23 cytokines, has a unique mechanism of action distinct from that of TNF antagonists. ⋯ Ustekinumab was generally well tolerated as both induction and maintenance therapy; serious infections and malignancies were rare. Thus, ustekinumab presents a promising alternative treatment option in patients with moderately to severely active Crohn's disease who have failed or are intolerant to treatment with conventional therapies or TNF antagonists.
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Cytotoxic chemotherapy has been the only systemic treatment of locally advanced and metastatic urothelial carcinoma for decades. Long-term survival remains stagnant around 12-14 months for patients with advanced disease who have progressed on or recurred after receiving first-line platinum-based chemotherapy. Improving clinical outcomes for patients with urothelial carcinoma in all disease settings requires the development of novel treatments, especially for patients who failed on first-line chemotherapy. ⋯ On March 16, 2017, results from the phase III trial KEYNOTE-045 demonstrated that survival was significantly longer in patients treated with pembrolizumab when compared with the standard second-line chemotherapy. Research into biomarkers such as PD-L1 expression, messenger RNA subtype, mutational and neoantigen load and gene signature expression will be crucial to determining why some patients respond to immunotherapy and others do not. This review article describes the advances in immunotherapy since the development of BCG, presents results from clinical trials investigating immune-checkpoint inhibitors and discusses biomarkers and prognostic factors associated with response to these new drugs.
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Opioid pharmacotherapies play an important role in the treatment of opioid-dependent women; however, very little is known about the safety of naltrexone in pregnant patients. ⋯ Opioid-dependent women treated with naltrexone implant had higher rates of birth than the other three groups (methadone- or buprenorphine-treated women, or age-matched controls). Overall rates of complications during pregnancy were elevated in naltrexone-treated women when compared with the control group, but were generally not significantly different to rates in methadone- or buprenorphine-treated women.
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Naltrexone may provide a suitable alternative to methadone and buprenorphine in the treatment of pregnant opioid-dependent women; however, little is known about its effects on neonatal morbidity and mortality. ⋯ The use of implant naltrexone during pregnancy was not associated with higher rates of negative birth outcomes compared with methadone- and buprenorphine-exposed neonates. Significantly, naltrexone and buprenorphine were not associated with the high rates of neonatal mortality or congenital anomalies seen in methadone-exposed neonates.
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Review
A Review of Phosphate Binders in Chronic Kidney Disease: Incremental Progress or Just Higher Costs?
As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. ⋯ Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.