Future Prescriber 

Abstract: Linaclotide is a guanylate cyclase agonist that promotes increased stool water content, which increases bowel movement frequency. It has recently received a positive opinion from the CHMP for the treatment of constipation-predominant IBS. In this Drug profile Steve Chaplin presents the clinical data relating to its efficacy and adverse events. Copyright © 2013 John Wiley & Sons, Ltd.

Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in many of the world’s Developed Countries.1 It is associated with significant impairment of quality of life and functional independence. There are two forms of the disease; the atrophic (dry) form, which involves loss of retinal pigment epithelial cells and photoreceptors resulting in diminished retinal function, and the neovascular (exudative, wet) form, characterised by choroidal neovascularisation (CNV) – often associated with subretinal fluid, haemorrhage and exudation, and subsequent scarring of the macula. This wet form of the condition accounts for 90 per cent of AMD blindness.2 Approximately 500 000 new cases of neovascular AMD are diagnosed annually world-wide.3 In the UK, there are approximately 245 000 people with neovascular AMD, and the condition is the cause of more than 50 per cent of the UK’s blind registration.4 The present treatment modalities for CNV are few and, at best, halt disease progression.5,6 Until 1995, thermal laser photocoagulation was the only treatment available,5 although it is now reser ved for use in only extrafoveal CNV (defined as more than 200μm from the centre). In the UK, the National Institute for Health and Clinical Excellence (NICE) issued guidance for the use of photodynamic therapy (PDT) for AMD in 2003. NICE recommended that patients with classic no occult subfoveal CNV (defined as a neovasular complex made up of more than 50 per cent classic CNV with no occult component in the rest of the lesion), with best corrected visual acuity of 6/12 to 6/60, be treated with PDT. PDT has been thoroughly investigated for all subtypes of subfoveal CNV.6 In addition, patients with predominantly classic lesions are currently treated in the UK as part of an ongoing trial, the verteporfin photodynamic therapy (VPDT) Cohort Study. As a result, a significant proportion of patients with CNV due to AMD are not currently eligible for any form of NICE approved treatments. The availability of any new treatment modalities in the NHS will, therefore, have a substantial public health impact. Understanding of the molecular mechanisms of CNV has increased in recent years.7 Neovasularisation in AMD is due to angiogenesis occurring in the choroid (see Figure 1). The vascular endothelial growth factor (VEGF) plays a pivotal role as a promoter of angiogenesis in CNV.8 The VEGF family consists D R U G P R O F I L E

Abstract: Gliptins represent an emerging new class of oral agents to treat type 2 diabetes. They act by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4). This enzyme inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones are released from the intestine during a meal and act on the pancreas to increase nutrient-stimulated insulin secretion. Thus DPP-4 inhibitors serve as incretin enhancers; they delay inactivation of GLP-1 and GIP, increasing the insulin response to a meal, which improves glycaemic control. This therapeutic approach carries a low risk of interprandial hypoglycaemia and does not cause weight gain. The first gliptin, sitagliptin (Januvia), was introduced in the UK in April 2007 as ‘add-on’ therapy for patients with type 2 diabetes inadequately controlled with metformin or a thiazolidinedione. Other gliptins, notably vildagliptin (Galvus), saxagliptin and alogliptin are advanced in clinical development. Copyright © 2007 John Wiley & Sons, Ltd.

Abstract: Apremilast, an orally active inhibitor of phosphodiesterase 4 that inhibits several inflammatory cytokines, is being developed for the treatment of psoriasis and psoriatic arthritis. This Drug profile reviews the clinical data to date. Copyright © 2013 John Wiley & Sons, Ltd.