A case for adoption of continuous albendazole treatment regimen for human echinococcal infections

TY - JOUR

T1 - A case for adoption of continuous albendazole treatment regimen for human echinococcal infections

AU - Tamarozzi, Francesca

AU - Horton, John

AU - Muhtarov, Marin

AU - Ramharter, Michael

AU - Siles-Lucas, Mar

AU - Gruener, Beate

AU - Vuitton, Dominique A.

AU - Bresson-Hadni, Solange

AU - Manciulli, Tommaso

AU - Brunetti, Enrico

N1 - Funding Information: This work was partly supported by the Italian Ministry of Health ?Fondi Ricerca Corrente ? Progetto L3P1? ? IRCCS Sacro Cuore Don Calabria Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.We thank Samuel Goblirsch for the support for text editing. Publisher Copyright: © 2020 Tamarozzi et al. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/9

Y1 - 2020/9

N2 - Cystic (CE) and alveolar (AE) echinococcosis are chronic, neglected parasitic diseases bur-dened 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 benzimid-azole 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 continu-ously 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 sched-ule, 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 perspec-tive. 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 seri-ous diseases.

AB - Cystic (CE) and alveolar (AE) echinococcosis are chronic, neglected parasitic diseases bur-dened 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 benzimid-azole 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 continu-ously 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 sched-ule, 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 perspec-tive. 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 seri-ous diseases.

UR - http://www.scopus.com/inward/record.url?scp=85091192793&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0008566

DO - 10.1371/journal.pntd.0008566

M3 - SCORING: Journal article

C2 - 32941434

AN - SCOPUS:85091192793

VL - 14

SP - e0008566

JO - PLOS NEGLECT TROP D

JF - PLOS NEGLECT TROP D

SN - 1935-2735

IS - 9

ER -