Comparative efficacy and safety of oral ivermectin, topical permethrin, and combination in the treatment of patients with classic scabies: systematic review and network meta-analysis.

backgroundOral ivermectin is commonly used as a second-line treatment for classic scabies, particularly in cases of treatment failure or poor adherence to topical permethrin, the standard of care. However, the comparative efficacy and safety of oral ivermectin, alone or in combination with permethrin, remains unclear. This systematic review and network meta-analysis evaluated the efficacy and safety of these treatments to guide clinicians and policymakers.

methodsOn April 17, 2022, we conducted a comprehensive search of databases, including MEDLINE and CENTRAL, as well as secondary sources for randomized controlled trials comparing oral ivermectin, alone or in combination with topical permethrin, and topical permethrin, or any of the three with other scabicides or placebo/vehicle/no treatment among patients with classic scabies. The primary outcomes were clinical cure and serious adverse events. We assessed the risk of bias using the Cochrane Risk of Bias 2.0 and evaluated the certainty of evidence using the GRADE approach. Network meta-analyses were performed using available case analysis and a random-effects model. Sensitivity and subgroup analyses explored the impact of methodologic decisions and known effect modifiers. Effect estimates and certainty of evidence ratings were presented in the Summary of Findings tables.

resultsWe included 38 RCTs (N = 4879), most of which had moderate or high overall risk of bias. Oral ivermectin, given in varying dosing regimens (single dose, two-dose, or flexible dosing) showed little or no difference in clinical cure rates compared to permethrin, which was also administered in different dosing schedules, at one to two weeks post-treatment (network RR 0.95, 95% CI [0.89, 1.02]; 30 RCTs, N = 3469; global inconsistency P = 0.42; low certainty evidence). Serious adverse events were rare (1/3212; 0.03%, 95% CI [0.000079, 0.17]; 29 RCTs; very low certainty evidence). One child who received oral ivermectin was hospitalized for cellulitis but eventually recovered. Limited data (1 RCT; n = 100) suggested that combination oral ivermectin/permethrin may be as effective or more effective than permethrin for clinical cure at one to two weeks (network RR 1.21, 95% CI [0.94, 1.56]; low certainty evidence).

conclusionThere may be little or no difference between oral ivermectin and permethrin in clinical cure. However, combination therapy with oral ivermectin and permethrin may be as good as or better than permethrin alone. The rate of serious adverse events is uncertain. Further well-designed RCTs should be conducted to confirm the findings and inform clinical practice and public health policy on scabies control. STUDY REGISTRATION: UPM RGAO-2021-1058; PHRR230322-005013; PROSPERO CRD42022278007.