Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Sacro Cuore Don Calabria Hospital, Department of Infectious-Tropical Diseases and Microbiology, Negrar, Verona, Italy.
Tropical Projects, Hitchin, United Kingdom.
PLoS Negl Trop Dis. 2020 Sep 17;14(9):e0008566. doi: 10.1371/journal.pntd.0008566. eCollection 2020 Sep.
Cystic (CE) and alveolar (AE) echinococcosis are chronic, neglected parasitic diseases burdened by high morbidity and, for AE, by high mortality, if left untreated. CE and AE have a widespread distribution, including Europe. Albendazole (ABZ), a broad-spectrum benzimidazole drug widely used to treat parasitic infections, is the drug of choice for the management of CE and AE, and is parasitostatic on echinococcal metacestodes. In Europe, ABZ is licensed for interrupted "cyclic" treatment, for a maximum of 3 cycles. However, better efficacy with no increased side effects has been shown when the drug is administered continuously and for longer periods. Current international recommendations, on the basis of clinical, pharmacological, and biological studies, recommend continuous administration of ABZ for months to years for the treatment of CE and AE, and this schedule has been widely in use for the past 20 years. However, in Europe this internationally recommended schedule, with the exception of France, is technically "off-label", and, as such, requires an informed consent by the patient and, in some countries, even precludes the reimbursement of the drug cost. Adding to the very high cost of the drug, frequent "out-of-stock" situation, and packaging format impractical for long therapies, these conditions put patients with CE and AE regularly at risk of treatment discontinuation and disease progression. European regulations envisage variations to marketing authorization, but postauthorization studies should be carried out by the holder of the license of the drug, in the form of randomized controlled trials. While such studies do not seem feasible and would probably not be ethically justified for CE and AE, European regulations envisage other possibilities in particular situations, which apply to CE and AE, but there is limited interest to invest in this perspective. We urge a coordination between stakeholders to find effective and feasible ways to take action to revise the benzimidazole dosage regimens for CE and AE and to ensure a fair, regular, and easy access to the appropriate treatment to those suffering from these serious diseases.
囊性(CE)和肺泡(AE)包虫病是慢性、被忽视的寄生虫病,发病率高,如果不治疗,AE 还会导致高死亡率。CE 和 AE 分布广泛,包括欧洲。阿苯达唑(ABZ)是一种广谱苯并咪唑类药物,广泛用于治疗寄生虫感染,是治疗 CE 和 AE 的首选药物,对包虫蚴有抑制作用。在欧洲,ABZ 被批准用于间断“周期性”治疗,最多 3 个周期。然而,连续和更长时间给药显示出更好的疗效,且没有增加副作用。基于临床、药理学和生物学研究,目前的国际建议推荐连续使用 ABZ 治疗 CE 和 AE 数月至数年,这一方案在过去 20 年中得到了广泛应用。然而,在欧洲,除法国外,这种国际推荐方案在技术上是“超适应证”的,因此需要患者知情同意,在一些国家甚至排除了药物费用的报销。此外,由于药物费用非常高、经常出现“缺货”情况以及不适合长期治疗的包装形式,这些情况使 CE 和 AE 患者经常面临停药和疾病进展的风险。欧洲法规设想对上市许可进行变更,但上市后研究应由药物许可证持有人以随机对照试验的形式进行。虽然对于 CE 和 AE,这种研究似乎不可行,也不太可能在伦理上得到证明,但欧洲法规在特殊情况下设想了其他可能性,这些可能性适用于 CE 和 AE,但对此类研究的兴趣有限。我们敦促利益相关者协调一致,寻找有效和可行的方法来修改 CE 和 AE 的苯并咪唑剂量方案,并确保那些患有这些严重疾病的人能够公平、定期和轻松地获得适当的治疗。