J Manag Care Spec Pharm. 2016 Oct;22(10-a-s Suppl):S3-S15. doi: 10.18553/jmcp.2016.22.10-a-s.s3.
Chronic liver disease and cirrhosis are a leading cause of morbidity and mortality in the United States. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis and which has been designated an orphan condition, is a chronic autoimmune disease resulting in the destruction of the small bile ducts in the liver. Without effective treatment, disease progression frequently leads to liver failure and death. Until May 2016, the only FDA-approved treatment for PBC was ursodiol (UDCA), an oral hydrophilic bile acid, which can slow progression of liver damage due to PBC. However, 1 out of 3 patients taking UDCA has an inadequate biochemical response, leading to increased risk of disease progression, liver transplantation, and mortality. Given this unmet clinical need, new therapies are in development for the treatment of PBC. To provide pharmacists with an overview of the latest research on the pathophysiology of PBC and potential new treatment options and to highlight medical and specialty pharmacy approaches to managing access to drugs to treat orphan diseases such as PBC, a 2-hour satellite symposium was presented in conjunction with the 2015 Academy of Managed Care Pharmacy (AMCP) Nexus meeting. Although obeticholic acid was approved by the FDA for the treatment of PBC in May 2016, this development occurred after the symposium presentation. The symposium was supported by an independent educational grant from Intercept Pharmaceuticals and was managed by Analysis Group. Robert Navarro, PharmD, moderated the CPE-accredited symposium titled "Medical and Specialty Pharmacy Management Update on Primary Biliary Cirrhosis." Expert panelists included Christopher L. Bowlus, MD; James T. Kenney, RPh, MBA; and Gary Rice, RPh, MS, MBA, CSP.
To summarize the educational satellite symposium presentations and discussions.
Autoimmune liver diseases, including PBC, are responsible for 15% of all liver transplants performed and an equal percentage of deaths related to liver disease. UDCA is the only FDA-approved therapy for treatment of PBC and is considered the standard of care. Nevertheless, many patients do not respond to UDCA, creating the need for new therapeutic options to improve clinical outcomes for PBC patients with inadequate response to treatment. While several agents are being studied in combination with UDCA, monotherapy with the novel agent obeticholic acid, a farnesoid X receptor agonist, has also shown promising results. Health plans are anticipated to assign any newly introduced therapy for the treatment of PBC to specialty pharmacy given its orphan disease status. This assignment enables the health plan to receive disease education, which is particularly important when new drugs are indicated for orphan diseases, and assistance with designing appropriate prior authorization criteria. The clinical value of any new therapeutic options that will inform formulary decisions and prior authorization criteria will be assessed based on evidence of efficacy, safety, and tolerability, among other factors, such as the potential to reduce or delay medical resource utilization (e.g., liver transplant). Key considerations for prior authorization of a new therapy will be determining which PBC patients are appropriate candidates for the new therapy and developing criteria for that determination. These are likely to include clinical diagnostic criteria and degree of response to prior treatment with UDCA. Initially, any new therapy would likely be positioned as noncovered until appropriate prior authorization criteria are established.
PBC is a chronic liver disease with significant morbidity and mortality, as well as a significant burden on the health care system if the disease progresses to the point at which a liver transplant is needed. Although UDCA, the current standard of care, has improved outcomes for many patients, others have an inadequate response to this treatment. This symposium discussed these issues and also addressed the overall treatment paradigm for orphan drug therapies, key implications for patient management, and the role of specialty pharmacy management and any associated needs both in general and specifically for new therapeutic options for PBC.
慢性肝脏疾病和肝硬化是美国发病率和死亡率的主要原因。原发性胆汁性胆管炎（PBC），以前称为原发性胆汁性肝硬化，已被指定为孤儿病，是一种慢性自身免疫性疾病，导致肝脏中小胆管的破坏。如果没有有效的治疗，疾病的进展通常会导致肝衰竭和死亡。直到 2016 年 5 月，FDA 批准的唯一治疗 PBC 的药物是熊去氧胆酸（UDCA），一种口服亲水性胆汁酸，可减缓 PBC 引起的肝损伤进展。然而，1/3 服用 UDCA 的患者生化反应不足，导致疾病进展、肝移植和死亡的风险增加。鉴于这种未满足的临床需求，正在开发新的治疗方法来治疗 PBC。为了让药剂师全面了解 PBC 的病理生理学和潜在新治疗方案的最新研究，并强调管理治疗 PBC 等孤儿病药物的途径的医疗和专科药房方法，在 2015 年管理医疗保健药房协会（AMCP）网络会议期间举办了一个 2 小时的卫星研讨会。尽管 obeticholic 酸于 2016 年 5 月被 FDA 批准用于治疗 PBC，但这一进展发生在研讨会报告之后。该研讨会得到了 Intercept 制药公司的独立教育资助，并由 Analysis Group 管理。Robert Navarro，PharmD 主持了题为“原发性胆汁性肝硬化的医疗和专科药房管理更新”的 CPE 认可研讨会。专家小组成员包括 Christopher L. Bowlus，医学博士；James T. Kenney，RPh，MBA；和 Gary Rice，RPh，MS，MBA，CSP。
总结教育卫星研讨会的演讲和讨论。
包括 PBC 在内的自身免疫性肝病占所有进行的肝移植的 15%，也是与肝脏疾病相关的死亡的 15%。UDCA 是唯一批准用于治疗 PBC 的 FDA 药物，被认为是标准护理。然而，许多患者对 UDCA 没有反应，这就需要新的治疗方案来改善对治疗反应不足的 PBC 患者的临床结果。虽然有几种药物正在与 UDCA 联合研究，但新型药物 obeticholic 酸的单药治疗，一种法尼醇 X 受体激动剂，也显示出了有希望的结果。鉴于其孤儿病的地位，预计健康计划将把任何新引入的治疗 PBC 的药物分配给专科药房。这种分配使健康计划能够获得疾病教育，这在新药物适用于孤儿病时尤为重要，并有助于设计适当的事先授权标准。任何新的治疗方案的临床价值将根据疗效、安全性和耐受性等因素，以及减少或延迟医疗资源利用（如肝移植）的潜力来评估，这些因素将用于告知配方决策和事先授权标准。新疗法事先授权的关键考虑因素将是确定哪些 PBC 患者是新疗法的合适候选者，并制定确定该疗法的标准。这些标准可能包括临床诊断标准和对先前 UDCA 治疗的反应程度。最初，任何新疗法都可能被定位为非覆盖范围，直到建立适当的事先授权标准。
PBC 是一种慢性肝脏疾病，具有显著的发病率和死亡率，如果疾病进展到需要肝移植的程度，还会对医疗保健系统造成重大负担。尽管 UDCA，目前的标准护理，已经改善了许多患者的预后，但其他人对这种治疗反应不足。本次研讨会讨论了这些问题，还讨论了孤儿病治疗药物的整体治疗模式、对患者管理的主要影响，以及专科药房管理的作用以及对 PBC 新治疗方案的一般和特定需求。
