High-Dose Ivermectin is Not Superior for Severe Scabies Treatment: NEJM

To rigorously investigate the effectiveness of dose escalation, a blinded randomized controlled trial was carried out among adults suffering from a severe (profuse or crusted) case of scabies. Mite infestation was scientifically confirmed among all subjects through either parasitological isolation or dermoscopy. Patients were randomly assigned in equal proportions into two experimental groups, where one received high-dose therapy, which involved the administration of 400 µg/kg of oral ivermectin, while the other received standard-dose therapy, which consisted of the administration of 200 µg/kg of oral ivermectin.

Both treatment groups received the oral ivermectin with meals on days 0, 7, and 14. The oral ivermectin therapy was complemented by the use of 5% topical permethrin cream from head-to-toe on days 0 and 7, as well as daily emollient cream for damaged skin barrier. The outcome measure of a complete cure was characterized by the total lack of mites, eggs, or feces on days 18 and 21, as well as the disappearance of active lesions on day 28.

Key findings:

• It was possible to conduct successful analysis among the total number of 132 adult subjects, 66 of whom were enrolled into the higher-dose cohort, and another 66 into the standard-dose cohort.
• A full cure could be obtained in 75.0% (49 out of 66) of those enrolled into the higher-dose group compared to 82.0% (54 out of 66) of those from the standard-dose group.
• The odds ratio (OR) for achieving a full recovery in the higher-dose group versus the standard-dose one was 0.64 (95% confidence interval, 0.25 to 1.67), thereby confirming lack of statistical significance for the higher dose.
• Both doses were tolerable and did not present any novel safety concerns or serious side effects.

This study shows that increased use of a 400 µg/kg dosage of oral ivermectin alongside 5% permethrin cream does not offer any advantage over the standard 200 µg/kg dosage regime in successfully treating severe scabies. This information will have practical applications for the global healthcare community and guidelines related to infectious diseases. Severe scabies often tends to afflict immunocompromised patients in poor communities, meaning that unnecessary escalation of drug dosages should be avoided for economic and safety reasons.

Reference:

Bernigaud, C., Do-Pham, G., Guichard, E., Beylot-Barry, M., Goujon, E., Isnard, C., Beneton, N., Samimi, M., Tedbirt, B., Adamski, H., Azib, S., Mahé, E., Michel, C., Perrot, J.-L., Acquitter, M., Bursztejn, A.-C., Chaby, G., Caux, F., Passeron, T., … Chosidow, O. (2026). Combined oral ivermectin and 5% permethrin cream to treat severe scabies. The New England Journal of Medicine, 394(18), 1814–1823. https://doi.org/10.1056/NEJMoa2411721