Onchocerca volvulus microfilariae in the anterior chambers of the eye and ocular adverse events after a single dose of 8 mg moxidectin or 150 µg/kg ivermectin: results of a randomized double-blind Phase 3 trial in the Democratic Republic of the Congo, Ghana and Liberia.

ABSTRACT

BACKGROUND: After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg skin, SmfD). Assuming long-term ivermectin use led to < 5 SmfD with little or no eye involvement, DEC + ivermectin + albendazole treatment a few months after ivermectin was proposed. In 2018, the US FDA approved moxidectin for treatment of O. volvulus infection. The Phase 3 study evaluated SmfD, microfilariae in the anterior chamber (mfAC) and adverse events (AEs) in ivermectin-naïve individuals with ≥ 10 SmfD after 8 mg moxidectin (n = 978) or 150 µg/kg ivermectin (n = 494) treatment. METHODS: We analyzed the data from 1463 participants with both eyes evaluated using six (0, 1-5, 6-10, 11-20, 21-40, > 40) mfAC and three pre-treatment (< 20, 20 to < 50, ≥ 50) and post-treatment (0, > 0-5, > 5) SmfD categories. A linear mixed model evaluated factors and covariates impacting mfAC levels. Ocular AEs were summarized by type and start post-treatment. Logistic models evaluated factors and covariates impacting the risk for ocular AEs. RESULTS: Moxidectin and ivermectin had the same effect on mfAC levels. These increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, respectively. Six and 12 months post-treatment, mfAC were detected in ≈5% and ≈3% of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of moxidectin- and 10.2% of ivermectin-treated participants without difference in type or severity. The risk for ≥ 1 ocular Mazzotti reaction increased for women (OR 1.537, 95% CI 1.096-2.157) and with mfAC levels pre- and 4 days post-treatment (OR 0 > 10 mfAC 2.704, 95% CI 1.27-5.749 and 1.619, 95% CI 0.80-3.280, respectively). CONCLUSIONS: The impact of SmfD and mfAC levels before and early after treatment on ocular AEs needs to be better understood before making decisions on the risk-benefit of strategies including DEC. Such decisions should take into account interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals.