O. 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

Abstract Background After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high O. volvulus microfilaridermia. Assuming long-term ivermectin use led to < 5 microfilariae/mg skin (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 ivermectin-naïve individuals with ≥ 10 SmfD for skin and ocular microfilariae and adverse events (AEs) for 12–18 months after a single treatment (8mg moxidectin, n = 978 or 150µg/kg ivermectin n = 494).Methods We descriptively analyzed the data from 1463 participants with both eyes evaluated using six (0, 1–5, 6–10, 11–20, 21–40, > 40) categories for microfilariae in the anterior chamber (mfAC) and three pre-treatment (< 20, 20-<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 of mfAC levels before and early after treatment on ocular AEs needs to be better understood before decisions on the risk-benefit of strategies including DEC. Such decisions should consider interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals.Trial registration The study was registered on 14 November 2008 in Clinicaltrials.gov (ID: NCT00790998).