Lesinurad: a novel therapeutic option in the pharmacotherapy of gout

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Current therapies for chronic gout include mainly allopurinol and febuxostat. Inspite of the availability of these medications for several years, a significant number of patients do not have adequate control of uric acid levels resulting in acute gout flares. Lesinurad is the most recent drug molecule approved by US FDA & EMA for the treatment of gout in patients with uncontrolled gout along with allopurinol. Lesinurad prevents reabsorption of uric acid from the renal tubules, resulting in uricosuria. The efficacy of the lesinurad was demonstrated in three randomized phase 3 controlled clinical trials where the drug was primarily evaluated in the setting of background therapy with allopurinol or febuxostat. There is a definite risk of nephrotoxicity with monotherapy and when the drug is used in patients who have inadequate renal function. The drug does appear to be relatively safe, though the inconclusive cardiovascular safety of the drug has prompted the regulatory agency to mandate post marketing trials to evaluate the safety of this molecule. Nevertheless, lesinurad does appear to have a lot of promise as a front line drug molecule in the control of hyperuricemia

Flibanserin: a serendipitous story

Female sexual disorders are increasingly being recognized in the population and hypoactive sexual desire disorder (HSDD) is one of the commonest sexual disorders among females. The prevalence of the disease varies between 10-20% in the Caucasian population. Testosterone is the only treatment that is approved by the European Medical Agency. Flibanserin is a drug that has been approved by the US FDA for HSDD among pre-menopausal women in 2015. Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist that rebalances the neural circuitry involved in processing sexual desire by reducing serotonin activity and enhancing dopamine and epinephrine activity. The efficacy of the drug was confirmed in three pivotal randomized placebo control trials in premenopausal women who consumed the drug for 24 weeks. There was a significant improvement in the number of sexually satisfying events. The most common safety concerns for flibanserin as seen in clinical trials were somnolence, hypotension and syncope. The drug is prescribed at a dose of 100 mg once daily at bed time. The marginal efficacy of the drug coupled with other safety concerns, such as hypo-tensions have given room for much criticism over the drug’s approval by the FDA. Nevertheless, on a positive note the serendipitous discovery of flibanserin and its repurposing for HSDD is a compelling narrative in its drug development history. It remains to be seen if the long term safety of the molecule and the efficacy of the molecule in non-trial settings could make it an attractive pharmaco-therapeutic option for HSDD

Empagliflozin: an exciting prospect in the treatment of diabetes

Type 2 diabetes mellitus (T2DM) continues to be a chronic and disabling disease that is associated with high mortality and morbidity. The epidemic burden of diabetes mellitus has increased in developing countries and Asia is considered as the “diabetic epicentre”. Type 2 diabetes (T2DM), is characterised by reduced secretion of insulin from pancreatic beta cells independently or associated with reduced response of peripheral tissues to circulating insulin. A proper glycaemic control is essential to delay the micro and macrovascular complications of T2DM. Standard anti-diabetic agents including insulin happen to induce minor to major adverse outcomes in certain populations over prolonged period of administration. Hence there has been a compelling need to develop newer and novel approach to treatment of T2DM. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel category of drugs that happen to reduce glycaemic overload by inducing glycosuria. The safety, efficacy and tolerability profile of these drugs were studied separately under various trials and was approved for use in August 2014 by US-FDA. This review is an attempt to describe the history of SGLT-2 inhibitors, their mechanism of action, safety and efficacy as well as its current status among anti-diabetic agents. 

Secukinumab - a stupendous option in psoriasis management

Psoriasis is a chronic inflammatory skin disease with increased epidermal proliferation related to dysregulation of the immune system. In spite of several therapeutic strategies available for the treatment of this condition, the disease causes untold suffering particularly in the severe variant of the disease. Secukinumab is a human IgG1 monoclonal antibody that binds to the cytokine interleukin-17A (IL-17A) inhibiting the pro-inflammatory effects that are involved in the development of plaque psoriasis. Secukinumab 300mg is to be given via subcutaneous injection at weeks 0, 1, 2, 3 and 4 and once monthly thereafter. The efficacy of secukinumab has been evaluated in three phase 3 clinical trials. The drug showed an overwhelming improvement in the primary end points as assessed by PASI 75 and modified IGA scores.  The only major concern with secukinumab is the increased risk of nasopharyngitis and mucocutaneous candidiasis due to the interference with host defence mechanisms by targeting IL-17.  Secukinumab has also shown favorable response in the treatment of psoriatic arthritis, ankylosing spondylitis from clinical trials. The drug has been approved by the US FDA in January 2015 for the treatment of moderate to severe psoriasis in patients who require systemic therapy. Nevertheless long term safety data are still awaited. While the results of these trials have been extremely gratifying, it remains to be seen if the stupendous performance displayed in clinical trials could be translated in real world practice

Aflibercept for diabetic macular edema: a concise review

Diabetic retinopathy and diabetic macular edema are associated with loss of vision in patients with diabetes worldwide. The treatment requires a multidisciplinary interventional approach. Among the available management options for DME, laser photocoagulation has been the standard of care. Due to its slow progression and inability to reverse the vision loss, an alternative treatment is needed. The role of vascular endothelial growth factors (VEGF) and inflammatory mediators led to the development of anti-VEGF agents, that stimulates retinal vasculogenesis and angiogenesis. Intravitreal aflibercept is an anti-angiogenic soluble decoy receptor with trap technology employed by fusion of multiple endogeneous receptor component, approved for the treatment of DME. Clinical trials of aflibercept comparing it with laser photocoagulation and other anti-VEGF have shown reliable efficacy, providing significantly positive visual and anatomical results. However, treatment regimens with monthly clinical visits and injections, challenge the patients comfort, thereby requiring the need to identify better strategies to lower injection frequencies

Association of galectin-3 with high cardiovascular risk in patients with type 2 diabetes attending a multi-specialty hospital in South India

Background: Diabetes mellitus is a chronic hyperglycemic condition that continues to be associated with high mortality and morbidity. Galectin-3 is a β-galactoside binding lectin and is a potential marker for inflammation, immunity and fibrosis. The aim of the study was to evaluate the relationship between Galectin-3 and baseline characteristics and to find the association between Galectin-3 and high cardiovascular risk in a group of Type-2 diabetes patients.Methods: A total of 100 patients with type-2 diabetes mellitus were included in the study after obtaining informed consent. The study participants were divided into two groups; those with diabetes for duration of less than 5 years as Group-1 and diabetes greater than 5 years as Group-2. Patients were also divided into three tertiles based on the Inter heart risk score (IHR). Five ml of blood was withdrawn from the ante-cubital vein and the serum obtained was subjected to analysis for estimating concentration of Galectin-3.Results: There was no significant difference between the Group-1 and Group-2 except gender variation with a significantly higher preponderance of males in Group 2. There was a significant correlation between Galectin-3 and parameters such as systolic blood pressure (r=0.033, p=0.03), creatinine (r=0.20, p=0.03), IHR (r=0.69, p=0.0001). Patients in the high risk category had greater levels of Galectin-3 compared to those with low and intermediate IHR.Conclusions: Galectin-3 concentration is elevated in diabetes patients and correlates with the IHR-Score. Thus Galectin-3 could be a useful biomarker for prediction of cardiovascular risk in diabetic subjects

Roflumilast: First approved oral selective PDE4 inhibitor for the treatment of COPD

Roflumilast is a first-in-class oral selective anti-inflammatory drug which is a PDE4 inhibitor. It has been approved by regulatory authorities in the Europe and US in 2010 and 2011 respectively for the prevention of acute exacerbations among patients with severe COPD. Since then, the drug has been studies in different populations in clinical trials as well as real world studies. The studies looked at different end points such as the quality of life, improvement in spirometry indices as well as the ability of the drug to prevent exacerbations and hospital admissions. There was a variable response seen in these studies.  This article seeks to review the evidence for the role of roflumilast in COPD from these recent studies since its approval. Keywords: Roflumilast, Exacerbation, Anti-Inflammatory, Phosphodiesterase, COP

Brodalumab: a promising option in the management of psoriasis

Brodalumab, a human monoclonal antibody approved as a biological therapy for treating psoriasis. Due to its consistent results across several clinical studies in treating patients with plaque psoriasis, in 2016 it was first approved worldwide in Japan followed by US FDA approval in 2017 and the European medicines agency. Brodalumab, selectively binds with higher affinity to IL-17RA, thereby blocking the actions of IL-17A, E and F. This act as a novel mechanism to inhibit the inflammation, hyperproliferation, skin thickening and other clinical symptoms associated with psoriasis. The safety and adverse effects of Brodalumab were similar to other IL-17 inhibitors, frequently reported adverse events were nasopharyngitis, neutropenia, and candidiasis. The FDA has recommended a boxed warning for the suicidal tendencies that could occur among Brodalumab users. This review is an endeavor to depict the drug's mode of action, pharmacokinetics, safety, and efficacy as well as its current status among other drugs targeting IL-17

Lesinurad: a novel therapeutic option in the pharmacotherapy of gout

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Current therapies for chronic gout include mainly allopurinol and febuxostat. Inspite of the availability of these medications for several years, a significant number of patients do not have adequate control of uric acid levels resulting in acute gout flares. Lesinurad is the most recent drug molecule approved by US FDA & EMA for the treatment of gout in patients with uncontrolled gout along with allopurinol. Lesinurad prevents reabsorption of uric acid from the renal tubules, resulting in uricosuria. The efficacy of the lesinurad was demonstrated in three randomized phase 3 controlled clinical trials where the drug was primarily evaluated in the setting of background therapy with allopurinol or febuxostat. There is a definite risk of nephrotoxicity with monotherapy and when the drug is used in patients who have inadequate renal function. The drug does appear to be relatively safe, though the inconclusive cardiovascular safety of the drug has prompted the regulatory agency to mandate post marketing trials to evaluate the safety of this molecule. Nevertheless, lesinurad does appear to have a lot of promise as a front line drug molecule in the control of hyperuricemia

Empagliflozin: an exciting prospect in the treatment of diabetes

Type 2 diabetes mellitus (T2DM) continues to be a chronic and disabling disease that is associated with high mortality and morbidity. The epidemic burden of diabetes mellitus has increased in developing countries and Asia is considered as the “diabetic epicentre”. Type 2 diabetes (T2DM), is characterised by reduced secretion of insulin from pancreatic beta cells independently or associated with reduced response of peripheral tissues to circulating insulin. A proper glycaemic control is essential to delay the micro and macrovascular complications of T2DM. Standard anti-diabetic agents including insulin happen to induce minor to major adverse outcomes in certain populations over prolonged period of administration. Hence there has been a compelling need to develop newer and novel approach to treatment of T2DM. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel category of drugs that happen to reduce glycaemic overload by inducing glycosuria. The safety, efficacy and tolerability profile of these drugs were studied separately under various trials and was approved for use in August 2014 by US-FDA. This review is an attempt to describe the history of SGLT-2 inhibitors, their mechanism of action, safety and efficacy as well as its current status among anti-diabetic agents.