A randomized double-blind,non-inferiority Phase II trial,comparing dapaconazole tosylate 2% cream with ketoconazole 2% cream in the treatment of Pityriasis versicolor

Objectives: The objective of this research was to evaluate the efficacy of a new antifungal imidazole, dapaconazole tosylate, in the treatment of Pityriasis versicolor (PV).

Design and methods: Sixty patients with clinical and mycological diagnosis of PV were randomly assigned to receive either 1 g dapaconazole tosylate 2% cream or 1 g ketoconazole 2% cream. Treatments were applied once a day for 28 days. A dermatologist evaluated efficacy and safety daily, and weekly laboratorial tests were performed. The primary end point was a clinical and mycological cure of lesions after 28 days of treatment. The secondary end point was the time to clinical healing assessed by Kaplan–Meier analysis and Log-rank testing.

Results: Fifty-three patients adhered to protocol rules. Clinical and mycological cure was achieved in 84.6% (22/26) and 92.6% (25/27) of patients treated with ketoconazole and dapaconazole, respectively (difference [effect size] = 8.0%, Standard error of difference: 8.69%, 95% CI: –6.3 to 22.3%). Median time to healing was 23.5 and 21 days for ketoconazole and dapaconazole, respectively (p = 0.126). Adverse events occurred only in ketoconazole-treated patients (13%; 4/30).

Conclusion: Dapaconazole tosylate is non-inferior to ketoconazole when used at a dose of 20 mg/day for 28 consecutive days for the treatment of PV. Dapaconazole also demonstrated a good safety profile.     

Anti-inflammatory agents to treat or prevent type 2 diabetes,metabolic syndrome and cardiovascular disease

Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease (CVD). These observations suggest that pharmacological strategies, which reduce inflammation, may be therapeutically useful in treating obesity, type 2 diabetes and associated CVD.

Area covered: The article covers novel strategies, using either small molecules or monoclonal antibodies. These strategies include: approaches targeting IKK-b-NF-kB (salicylates, salsalate), TNF-α (etanercept, infliximab, adalimumab), IL-1β (anakinra, canakinumab) and IL-6 (tocilizumab), AMP-activated protein kinase activators, sirtuin-1 activators, mammalian target of rapamycin inhibitors and C-C motif chemokine receptor 2 antagonists.

Expert opinion: The available data supports the concept that targeting inflammation improves insulin sensitivity and β-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammatory rheumatoid diseases as well in patients with metabolic syndrome or T2DM. Although promising, the observed metabolic effects remain rather modest in most clinical trials. The potential use of combined anti-inflammatory agents targeting both insulin resistance and insulin secretion appears appealing but remains unexplored. Large-scale prospective clinical trials are underway to investigate the safety and efficacy of different anti-inflammatory drugs. Further evidence is needed to support the concept that targeting inflammation pathways may represent a valuable option to tackle the cardiometabolic complications of obesity.     

Advances in treating drug-resistant hepatitis B virus in HIV-infected patients

Introduction: Treatment of HIV infection with nucleos(t)ide analogs active against hepatitis B virus (HBV) highly improves hepatic outcomes in HIV-HBV coinfected patients, especially when tenofovir (TDF) is part of the antiviral regimen. Drug resistance has been the major drawback and must remain as the most important caveat when planning to treat dually or HIV and HBV independently in coinfected patients.

Areas covered: The use of lamivudine (LAM) as the only active anti-HBV agent should strongly be discouraged in HIV-HBV coinfected patients, although it might be considered for individuals with low serum HBV-DNA and in the absence of liver cirrhosis as an exception. In any other case drug resistance may cause any clinical benefit of this antiviral HBV therapy to disappear, and lead to cross-resistance with other antivirals and even occasionally select for HBV vaccine escape mutants. In cirrhotics, liver enzyme flares may be accompanied by life-threatening decompensation. Entecavir is generally not recommended as an anti-HBV agent in HIV-HBV coinfected patients given its low residual antiretroviral activity and potential for selection of resistance mutations in HIV. Adefovir is not active against HIV using HBV dosing and is no longer recommended as HBV therapy given its limited antiviral effect. Finally, telbivudine is not active against HIV, it is less potent than TDF against HBV and depicts low barrier to resistance and cross-resistance to LAM or emtricitabine.

Expert Opinion: The introduction of TDF has drastically reduced the clinical relevance of hepatitis B drug resistance in HIV-HBV coinfected individuals. The use of LAM as the only active anti-HBV agent should strongly be discouraged in this population.