Drugs

Lomonaco, Romina; Sunny, Nishanth; Bril, Fernando; Cusi, Kenneth

doi: 10.1007/s40265-012-0004-0pmid: 23329465

Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disorder in the Western world. It is commonly associated with insulin resistance, obesity, dyslipidaemia, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Nonalcoholic steatohepatitis (NASH) is characterized by steatosis with necroinflammation and eventual fibrosis, which can lead to end-stage liver disease and hepatocellular carcinoma. Its pathogenesis is complex, and involves a state of ‘lipotoxicity’ in which insulin resistance, with increased free fatty acid release from adipose tissue to the liver, play a key role in the onset of a ‘lipotoxic liver disease’ and its progression to NASH. The diagnosis of NASH is challenging, as most affected patients are symptom free and the role of routine screening is not clearly established. A complete medical history is important to rule out other causes of fatty liver disease (alcohol abuse, medications, other). Plasma aminotransferase levels and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for a definitive diagnosis. However, there is an active search for plasma biomarkers and imaging techniques that may non-invasively aid in the diagnosis. The treatment of NASH requires a multifaceted approach. The goal is to reverse obesity-associated lipotoxicity and insulin resistance via lifestyle intervention. Although there is no pharmacological agent approved for the treatment of NAFLD, vitamin E (in patients without T2DM) and the thiazolidinedione pioglitazone (in patients with and without T2DM) have shown the most consistent results in randomized controlled trials. This review concentrates on our current understanding of the disease, with a focus on the existing therapeutic approaches and potential future pharmacological developments for NAFLD and NASH.

Caporali, Roberto; Todoerti, Monica; Sakellariou, Garifallia; Montecucco, Carlomaurizio

doi: 10.1007/s40265-013-0008-4pmid: 23335134

Interest in the numerous benefits of corticosteroid medication in the management of rheumatoid arthritis (RA) goes back to the mid-1950s, and has recently been renewed. The established evidence of their rapid symptomatic effects, along with the growing recognition of their long-lasting disease-modifying properties and preliminary data about their sub-clinical action, led us to reconsider the potential of corticosteroids in the treatment of RA, given their acceptable safety profile, especially when used at low dosages. Over time, several corticosteroid-based therapeutic approaches have been explored in order to optimize their clinical benefits, while limiting the adverse effects. Clinical data reported with initial high-dosage corticosteroid schedules with subsequent step-down schemes suggest clinical efficacy, but are not applicable to patient management in a real-life setting. Encouraging results on the clinical and sub-clinical effects of low dosages have led to a shift in usual daily practice. We present past and recent efforts to clarify the role of corticosteroids in the treatment of RA, focusing on the best approach in terms of dose and timing of corticosteroid administration. Additional information about different routes of administration, step-down schedules and adverse effects are also considered.

Hoy, Sheridan

doi: 10.1007/s40265-013-0006-6pmid: 23338539

A subcutaneous formulation of bortezomib is now indicated in the EU and the US for the treatment of patients with multiple myeloma. This article reviews pharmacological, therapeutic efficacy and tolerability data relevant to the utilization of subcutaneous bortezomib (Velcade®) in the treatment of patients with multiple myeloma. In a randomized, nonblind, phase III study, subcutaneous bortezomib was noninferior to intravenous bortezomib in the treatment of adults with relapsed multiple myeloma, as determined by the overall response rate after four cycles of therapy (primary endpoint). No significant differences between the subcutaneous and intravenous bortezomib formulations were observed in the median time to first response, median progression-free survival, median time to progression and 1-year overall survival. Compared with intravenous bortezomib, subcutaneous bortezomib confers a significant advantage with respect to the incidence of peripheral neuropathy (all grades, grade ≥2 and grade ≥3). As a consequence, it provides a new treatment option for patients with multiple myeloma, particularly those with pre-existing neuropathy or at a high risk of developing peripheral neuropathy.

Keating, Gillian

doi: 10.1007/s40265-012-0005-zpmid: 23329466

Extended-release ranolazine (ranolazine ER) [Ranexa®] is an antianginal agent that achieves its effects via a novel mechanism of action (inhibition of the late phase of the inward sodium current), without affecting heart rate or blood pressure (BP). This article reviews the efficacy, safety and tolerability of ranolazine ER as add-on therapy in patients with chronic stable angina pectoris, as well as summarizing its pharmacological properties and its use in non-ST-elevation acute coronary syndromes. In the CARISA and ERICA trials, add-on therapy with ranolazine ER improved exercise tolerance and/or reduced angina frequency and nitroglycerin use in patients with chronic stable angina; benefits were seen across a variety of patient subgroups. Although results of the MERLIN-TIMI 36 trial do not support the use of ranolazine ER in the acute management of non-ST-elevation acute coronary syndromes, they do support its use as an antianginal therapy. Ranolazine ER was generally well tolerated, with the most commonly reported adverse events including dizziness, nausea, asthenia and constipation. Despite being associated with modest increases in the corrected QT interval, ranolazine ER demonstrated antiarrhythmic effects in the MERLIN-TIMI 36 trial. In conclusion, ranolazine ER provides an important option for use as add-on therapy to reduce symptoms in patients with chronic stable angina.

Deeks, Emma D.

doi: 10.1007/s40265-013-0009-3pmid: 23338540

Certolizumab pegol (Cimzia®) is a recombinant, polyethylene glycolylated, antigen-binding fragment of a humanized monoclonal antibody that selectively targets and neutralizes tumour necrosis factor (TNF)-α. The drug is indicated for subcutaneous use every 2 or 4 weeks (q2w or q4w) for the treatment of adults with moderate to severe active rheumatoid arthritis (RA). The efficacy of subcutaneous certolizumab pegol in adults with active RA has been investigated in several well designed, placebo-controlled trials. In four pivotal studies of ≤52 weeks duration, patients with moderate to severe disease receiving recommended dosages of certolizumab pegol (200 mg q2w or 400 mg q4w), either as monotherapy (after failing prior disease-modifying anti-rheumatic drug [DMARD] therapy) or in combination with methotrexate (after responding inadequately to methotrexate alone), experienced rapid clinical improvement, with some combination trials also demonstrating inhibition of radiographic progression. The beneficial effects of certolizumab pegol therapy were generally maintained for up to ≈5 years in clinical trial extensions in which the drug was administered at dosages of 400 mg q4w or q2w. Additional studies suggest certolizumab pegol is also effective in patients who are Asian or have low to moderate disease activity, as well as more clinically representative patient populations. The tolerability profile of certolizumab pegol was acceptable, with infections/infestations the most common adverse events. Thus, certolizumab pegol is an effective option for the management of active RA in adults, although additional long-term and comparative efficacy and tolerability data are needed to help definitively position certolizumab pegol relative to other biological DMARDs, particularly other anti-TNF agents.

Deeks, Emma

doi: 10.1007/s40265-013-0012-8pmid: N/A