Overkill: Higher ivermectin dose less effective than standard dose for treating severe scabies

A higher dose of ivermectin when treating scabies was less effective than the standard dose of ivermectin when combined with a topical therapy, according to the results of a French study recently published in the New England Journal of Medicine.

The study was conducted at French dermatology clinics between October 2017 and January 2022 by a team of researchers, including Olivier Chosidow, M.D., Ph.D., of Bicêtre Hospital in Le Kremlin-Bicêtre, France.

Chosidow and his colleagues found that 75% of patients who received the 400 μg/kg dose were cured, compared with 82% of patients who were cured taking the standard 200 μg/kg dose.

Scabies is a contagious skin condition caused by Sarcoptes scabiei mites that burrow into the skin, causing an intensely itchy red rash that is highly contagious. There are different types of scabies infestations, ranging from “classic” scabies, which involves 10 to 15 mites, to “severe” scabies, which was the focus of this study.

Severe scabies infections are often resistant to treatment and sometimes multiple measures must be taken to get the infection under control, including hospitalization, environmental disinfection and repeated use of ivermectin and topical scabicides. The recommended dose and frequency of oral ivermectin have also been debated. The cure rate also varied widely, with the above measures contributing to a cure rate of between 30% and 100%.

The umbrella of severe scabies includes crusted scabies, which involves thousands of mites, manifesting as red scaly lesions in areas uncommon for scabies to infest, including the scalp, head and neck.

This study included two cohorts of 133 participants total. Each participant was randomized 1:1 and given either a dose of 400 μg/kg or a standard dose of 200 μg/kg for 28 days. All participants used emollient cream daily plus applied a 5% permethrin cream on days 0 and 7 overnight on their entire skin surface. Ivermectin was given on 0, 7 and 14. The study defined a “cure” by several measures, including the absence of mites on days 18 and 21 and the absence of active lesions by day 28.

"Larger randomized trials should be designed to determine whether the 82% probability of cure of severe scabies with standard-dose ivermectin can be improved," Chosidow and his colleagues wrote in the study. Strategies for how to attain higher percentages and potentially faster rates of cure include prolonged administration of oral ivermectin, more frequent applications of possibly different topical scabicides plus keratolytic agents to enhance their penetration into thickened skin; or administration of moxidectin a macrocyclic lactone with a longer half-life than ivermectin."

Some subgroups are more at risk than others, specifically older adults and migrants living in overcrowded areas, the study says. Severe scabies can also be deadly because infestations can lead to secondary bacterial infections from prolonged scratching. For this reason, people living in settings such as nursing homes, prisons and hospitals can be at risk if an outbreak occurs.

Serious adverse events occurred in eight patients, including two deaths in the higher-dose group, attributed to cardiac decompensation. There were also two deaths in the standard dose group, resulting from neurologic and cardiac failure, the study authors note.