Treatment Patterns and Persistence With GLP-1 RA Treatments Among Patients With Type 2 Diabetes in France: A Retrospective Cohort Analysis.

INTRODUCTION: In type 2 diabetes (T2D), persistence with injectable glucose-lowering therapy is associated with better outcomes. This study used real-world pharmacy data to report on persistence with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D in France. METHODS: This retrospective cohort analysis presents longitudinal data from approximately 7500 French retail pharmacies that filled GLP-1-RA prescriptions for GLP-1 RA-naïve patients with T2D ('index therapy': dulaglutide; once-weekly exenatide [exenatide QW]; twice-daily exenatide [exenatide BID]; liraglutide) between January 2015 and December 2016 (follow-up ≥ 12 months). The main outcome was treatment persistence (absence of discontinuation [gap following index therapy prescription ≥ 2-fold the expected duration of that prescription] or switch [new non-index glucose-lowering prescription issued ≤ 30 days before/after index therapy discontinuation]). Persistence was calculated as the median duration through Kaplan-Meier survival analysis over the variable follow-up period and as the proportion of patients persistent at 12 months. In addition to persistence outcomes (discontinuation/switch), three other treatment modifications were assessed: augmentation/intensification with a new non-index glucose-lowering therapy; off-label dose increase (daily dose > 20 µg for exenatide BID; two consecutive prescriptions with daily dose > 1.8 mg for liraglutide); and off-label dose decrease (two consecutive prescriptions with average daily dose lower than the index dose). Off-label dose changes were not assessed for dulaglutide or exenatide QW (as single-dose, prefilled pens). RESULTS: Median persistence was longest for dulaglutide (373 days) versus liraglutide (205 days), exenatide QW (184 days) and exenatide BID (93 days). Twelve months after treatment initiation, the percentage of persistent patients ranged from 51% (dulaglutide) to 21% (exenatide BID). Overall, treatment modification occurred less commonly for dulaglutide than for the other index GLP-1 RAs. CONCLUSION: This analysis revealed marked differences in persistence among GLP-1 RAs, which was highest for dulaglutide and lowest for exenatide BID. The prospective TROPHIES study will provide additional information about persistence with dulaglutide and liraglutide, including reasons for treatment modifications.

Patients with type 2 diabetes (T2D) who continue to take injectable glucose-lowering therapy for the duration of time recommended by their physician (i.e. those who are 'persistent') usually have better outcomes than those who do not. Persistence may be quantified as the "the duration of time from initiation to discontinuation of therapy". Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are glucose-lowering agents that are often used as the first injectable drug if oral treatments are no longer effective. The aim of the current study was to use data from approximately 7500 retail pharmacies to report persistence with each of four GLP-1 RAs (dulaglutide, once-weekly exenatide [exenatide QW], twice-daily exenatide [exenatide BID] or liraglutide) in GLP-1 RA-naïve patients with T2D in France. Patients (N = 15,074) initiated treatment between January 2015 and December 2016 and were followed for ≥ 12 months. The total duration of follow-up varied among patients. Among patients, persistence over the variable follow-up period was highest for dulaglutide and lowest for exenatide BID: median persistence was longer for dulaglutide (373 days) than for liraglutide (205 days), exenatide QW (184 days) or exenatide BID (93 days). Twelve months after treatment initiation, the percentage of persistent patients ranged from 51% (dulaglutide) to 21% (exenatide BID), with intermediate values for exenatide QW (35%) and liraglutide (36%). This analysis has revealed marked differences in the persistence of patients for various GLP-1 RAs, with patients on dulaglutide showing the highest persistence and those on exenatide BID the lowest.

New therapies for hepatitis C: considerations in patients with renal impairment.

Hepatitis C virus (HCV) is a major public health issue because infection may lead to liver failure, cirrhosis and hepatocellular carcinoma. In patients with renal dysfunction, hepatitis C can also worsen the underlying renal disease. Treating HCV infection is thus mandatory in this population. New therapies for hepatitis C have recently been developed, and some have been launched. Most of them are used in combination with the current standard of care, ribavirin and pegylated interferon alfa. Some of them can be used in regimens without ribavirin and/or pegylated interferon. However, few data are available on dosage adjustment for renal function in patients receiving these very new drugs. We reviewed the literature on this subject and gathered information, although scarce, to propose guidelines for using these drugs in patients with chronic kidney disease.

Acute renal failure associated with the new BRAF inhibitor vemurafenib: a case series of 8 patients.

BACKGROUND: Vemurafenib is a BRAF inhibitor that has become the cornerstone of metastatic or inoperable melanoma therapy since its approval in 2011 in the United States and 2012 in Europe. This targeted therapy has shown impressive results in terms of increased progression-free and overall survival as compared to dacarbazine. The safety profile did not include any renal manifestations at that time. METHODS: This report is the first case series of 8 patients who experienced significant to severe renal insufficiency under vemurafenib treatment. RESULTS: This case series shows that vemurafenib may induce potentially severe acute renal failure, including renal sequelae and persistent kidney disease in some cases. CONCLUSIONS: Further studies are needed to investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function should be closely monitored in treated patients for early detection of any renal dysfunction occurrence. Cancer 2014;120:2158-2163. © 2014 American Cancer Society.

Malaria prophylaxis in patients with renal impairment: a review.

Malaria is an endemic and potentially lethal disease transmitted by the protozoan parasite Plasmodium. It is currently endemic in more than 100 countries, which are visited by 125 million international travellers every year. For dialysis and renal insufficiency patients it becomes increasingly easier to travel to these countries thanks to the recent advances in renal replacement therapy. However, the pharmacokinetics of some prophylactic agents in malaria are altered, which may modify the effectiveness and safety of such treatments and the way they should be prescribed. Clinicians should be aware of these alterations which require subsequent dosage adjustments. This review provides recommendations on the use of antimalarial drugs, alone or in combination, in patients with renal impairment. These recommendations depend on the prevalence of Plasmodium falciparum chloroquine resistance, as defined by the WHO. Furthermore, fixed-dose combinations cannot be used in patients with creatinine clearance below 60 mL/min since the tablets available do not allow appropriate dosage adjustment for each drug. Chloroquine and proguanil require dosage adjustments, while atovaquone, doxycycline and mefloquine do not.

Pulmonary hypertension: use of oral drugs in patients with renal insufficiency.

Pulmonary hypertension (PH) is a progressive, fatal pulmonary circulatory disease that is characterized by elevated pulmonary arterial pressure and secondary right ventricular failure. PH has been reported to be highly prevalent in patients with chronic kidney disease, and especially among end-stage renal disease patients undergoing haemodialysis. However, only few data are available on drug dosage adjustment to renal function for those drugs that are commonly used in the treatment of PH. We reviewed the literature and gathered information, although sparse, to propose guidelines for using these drugs in renal insufficiency patients.

[How to adjust the dose of drugs in chronic kidney disease?]. / Comment adapter la dose des médicaments dans la maladie rénale chronique?

Renal insufficiency is a common disease, in the general population as well as in some specific diseases such as HIV infection or cancer. The vast majority of medicines require a dosage adjustment in case of renal dysfunction, it is thus of a crucial importance to know how to evaluate appropriately renal function, on one hand, but also to have access to reliable information sources on how to handle the drugs in such cases. Most often, the Summary of Drug Characteristics (SmPC) only provides partial information, which may even be false in some cases as compared to the most recent data from the literature. However, some information sources exist, reliable, updated, and easily accessible.

[How to evaluate renal function in cancer patients]. / Évaluation de la fonction rénale chez le patient atteint de cancer.

The evaluation of renal function in patients with cancer is necessary. Measuring the actual glomerular filtration rate of the patient is the gold standard. This is usually done using a measure of the renal clearance of a marker of glomerular filtration rate (inulin) or a radio-marker (EDTA Chrome 51, (51)Cr-EDTA). However, these measures are complex and very constraining for the patient and in terms of organization and equipment. It is possible to estimate renal function by calculation. There are in the literature many evaluation formulae available. However, it is essential to use a tool reliable enough to determine an appropriate estimate of renal function, and adjust the doses of treatment if necessary. The choice of the abreviated MDRD (aMDRD) formula is so far the recommended option in oncology.