Considerations for optimal management of patients with pulmonary arterial hypertension: a multi-stakeholder roundtable discussion.

A roundtable panel of national and regional managed care decision makers and providers met to discuss pulmonary arterial hypertension (PAH) and strategies for management. As a rare, complex disease with high economic costs and potentially devastating outcomes, PAH necessitates that managed care providers balance optimal care with efficient use of healthcare resources. PAH specialists are recognized by health plans as knowledgeable experts and integral partners in managing patients and resources. The diagnosis of PAH must be confirmed by a right heart catheterization. Available therapies are indicated almost exclusively for patients with PAH (riociguat is also indicated in chronic thromboembolic pulmonary hypertension) and target 1 of 3 pathways: endothelin receptor antagonists for the endothelin pathway; phosphodiesterase type-5 inhibitors and soluble guanylate cyclase stimulators for the nitric oxide pathway; and prostanoids as well as a prostacyclin receptor agonist for the prostacyclin pathway, with combination therapy becoming more common. Even in the modern treatment era, as shown in the REVEAL and French registries, PAH is often diagnosed years after symptoms first appear, which leads to a poor prognosis and increased burden on the healthcare system. Facilitating treatment of patients with PAH through centers of excellence, and coordinating care management between health plans and providers with evidence-based approaches can lead to both better results for patients and lower healthcare costs. When PAH experts have access to the right treatments for the right patients at the right time, they can work with insurers to improve the health of patients with PAH while helping to reduce the impact on the healthcare system.

The spectrum of irritable bowel syndrome: A clinical review.

BACKGROUND: Irritable bowel syndrome (IBS) is associated with a substantial burden on individual patients, health care systems, and society as a whole. OBJECTIVES: This review article provides an overview of the disease state and discusses treatment options. METHODS: The MEDLINE database was searched for original research and review articles published in English (from 1966 to July 2005) using the medical subject heading irritable bowel syndrome and the following subheadings: diagnosis, economics, pathophysiology, and therapy. Preference was given to articles that focused on new insights regarding pathophysiology and to those that addressed global symptom improvement for IBS. RESULTS: Symptoms of IBS vary with each patient and disease episode. Although improvement in individual IBS symptoms is desirable, the overall goal in managing patients with IBS is to achieve global symptom improvement. Traditional IBS therapies (ie, psychotherapy/behavioral therapy, bulking agents, antidiarrheals, antispasmodics, and tricyclic antidepressants) have lacked demonstrable efficacy in randomized controlled trials. Recent improvements in the understanding of IBS pathophysiology, particularly regarding the role of neurotransmitters and hormones in gastrointestinal motility, secretion, and visceral perception, have resulted in the development of novel treatments for IBS. In clinical trials, IBS-specific treatments (ie, agents that affect serotonergic pathways) have been associated with significant improvements in global symptoms. However, the added cost of treatment with these agents and the potential risks of serious adverse events (eg, severe constipation, severe diarrhea, ischemic colitis) may preclude their widespread use. Initial cost-effectiveness analyses with the novel IBS-specific agents suggest the benefits may outweigh the added costs. From a managed care perspective, the costs incurred by IBS-specific therapies may be offset by subsequent reductions in health care resource utilization by patients with IBS. CONCLUSIONS: IBS-specific agents offer an opportunity for patients with IBS to achieve global symptom improvement. However, when weighing the costs and potential risks against the potential benefits, clinicians should consider the nature and severity of the patient's symptoms, the degree of functional impairment, and the presence of psychosocial comorbidities.

Incretin mimetics: promising new therapeutic options in the treatment of type 2 diabetes.

OBJECTIVE: To review the current state of diabetes treatment from a clinical and management perspective and explore the role that new biologic pharmaceuticals may offer patients who fail to meet or maintain glycemic goals with existing treatment options. SUMMARY: Key clinical areas involve the role that insulin resistance and beta-cell dysfunction/failure play in the progression of type 2 diabetes as well as current treatment modalities and how they address those core defects. Management issues include a discussion of the economics of the disease and the implications of the United Kingdom Prospective Diabetes Study (UKPDS)--that good glucose control reduces the occurrence of microvascular complications and improves quality of life for diabetic patients. While an intensive approach may be costly in the short term, statistics on the rising pandemic of the disease argue compellingly for early and aggressive treatment to delay fatal complications and improve the quality of life for persons suffering from type 2 diabetes. Current pharmaceutical regimens are not successfully enabling patients with type 2 diabetes to reach glycemic goals. The ramifications of this failure have profound repercussions in the managed care organization environment. Fortunately, new treatment modalities are in various stages of development. These will be reviewed with a more in-depth exploration of the potential of incretin mimetics, a new biologic, injectable class of drugs for the treatment of type 2 diabetes. Emphasis will be given to exenatide, an incretin mimetic that demonstrates particular efficacy for patients not achieving glycemic goal with oral medications and are insulin naive. Biologics are administered by injection or infusion and are generally costly. Apart from their cost, however, what is even more critical to managed care executives and decision makers is that these medications indicate a trend in pharmacotherapy, a groundswell of new medications. In addition, few practitioners and even fewer health care executives understand molecular medicine. The key message is that making formulary decisions about these pharmaceuticals will become more pressing every year. CONCLUSION: Managed care executives will be faced with the significant challenge of investing their limited resources in the most clinically and fiscally responsible manner within a milieu of ever increasing pharmacologic options that could significantly strain budgets and result in less than optimal patient outcomes.

Clinical trial designs in PAH: shifting from functional measurements to long-term clinical outcomes.

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature that leads to right ventricular dysfunction, right ventricular failure, and premature death. There are a number of medications already on the market, representing different therapeutic classes and possessing multiple mechanisms of action. Three new agents were approved by the US Food and Drug Administration in 2013, and others are currently in development. Recent advancements in PAH have resulted in increased survival and improved quality of life; however, no therapy provides a cure. Experts in the field are now utilizing clinical trial designs and end points that better reflect the disease progression among patients with this chronic disease. Although randomized placebo-controlled monotherapy trials are considered the strongest design, ethical and practical considerations have led to an increasing number of randomized trials designed to compare a PAH-specific treatment with placebo as an add-on to standard therapy. As many patients who enroll in clinical trials are already being treated for their condition, it may be unethical to withdraw or delay lifesaving therapies. The most widely used primary end point for PAH trials, change in 6-minute walk distance (6MWD) from baseline, has substantial limitations. Although it is generally reproducible, inexpensive, and relatively easy to conduct, the 6MWD is not designed to assess disease progression. Recent data have shown that 6MWD has inconsistent correlation with key indicators of disease progression such as hospitalization due to PAH, worsening right-sided heart failure, and death. The Task Force on End Points and Clinical Trial Design that met at the 4th World Symposium on Pulmonary Hypertension (WSPH) in 2008 in Dana Point, California, questioned the clinical relevance of the 6MWD as a primary end point and recommended the use of a composite end point--time to clinical worsening (TTCW)--in phase 3 or pivotal trials. TTCW may include time from randomization to PAH-related hospitalization, need for interventional procedures (ie, lung transplantation or balloon atrial septostomy), and mortality. More recently, at the 5th WSPH, held in 2013 in Nice, France, experts reiterated these recommendations. They further noted that, as clinical trials increasingly allow background therapies and are longer in duration, it may be more meaningful to use primary end points that measure "clinical worsening" rather than 6MWD. This paradigm shift will not only lead to a clearer demonstration of efficacy and safety as new agents come on the market, but will provide important information on long-term benefits (ie, the effects of drugs on clinical deterioration) that can assist payers as they strive to make value-based formulary decisions and provide cost-effective high-quality care.

Pulmonary arterial hypertension: progress and challenges in the modern treatment era.

Pulmonary arterial hypertension (PAH) is a chronic, progressive disease with an estimated incidence of 2 cases per million individuals per year and a prevalence of approximately 10 to 15 cases per million individuals. PAH is more common in certain groups of patients, such as those with connective tissue disease and congenital heart disease, and is often overlooked in patients with these comorbidities. Treatment options in the United States have expanded to include 12 PAH-specific therapies, 3 of which were approved in 2013. As a result of treatment advancements, PAH patients are living longer. However, many challenges remain. Resource utilization in PAH, a primary driver of which is hospitalization, imposes a major economic burden on patients, payers, and society. Because change in 6-minute walk distance and other historical measures do not correlate well with the risk of hospitalization, guidelines favor more rigorous composite assessments of efficacy that take into account clinical worsening, including mortality and hospitalization. Stakeholders, including providers and payers, are tasked with selecting treatments with the best evidence of clinical benefit. Managing adherence to those therapies remains an important priority in improving clinical outcomes and reducing the overall clinical and economic burden of PAH. Future research that includes patient-reported outcomes, particularly those that reflect health-related quality of life, may be of particular relevance in this complex disease.