Ivermectin and permethrin for treating scabies

Stefanie Rosumeck; Alexander Nast; Corinna Dressler

doi:10.1002/14651858.CD012994

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Figure 1

Study flow diagram.

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Figure 2

‘Risk of bias' summary: review authors' judgements about each risk of bias item for each included trial.

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Figure 3

Forest plot of comparison: 1 Ivermectin 200 μg/kg versus permethrin 5% cream, outcome: 1.1 Complete clearance ‐ week 1.

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Figure 4

Forest plot of comparison: 1 Ivermectin 200 μg/kg versus permethrin 5% cream, outcome: 1.2 Complete clearance ‐ week 2.

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Figure 5

Forest plot of comparison: 1 Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications), outcome: 1.3 Complete clearance ‐ week 4.

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Figure 6

Forest plot of comparison: 1 Ivermectin 200 μg/kg versus permethrin 5% cream, outcome: 1.5 Number of participants with ≥ 1 adverse event ‐ week 4.

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Analysis 1.1

Comparison 1 Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications), Outcome 1 Complete clearance ‐ week 1.

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Analysis 1.2

Comparison 1 Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications), Outcome 2 Complete clearance ‐ week 2.

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Analysis 1.3

Comparison 1 Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications), Outcome 3 Complete clearance ‐ week 4.

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Analysis 1.4

Comparison 1 Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications), Outcome 4 Subgroup analysis for 1.3.2 ‐ complete clearance ‐ week 4.

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Analysis 1.5

Comparison 1 Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications), Outcome 5 Number of participants with ≥ 1 adverse event ‐ week 2.

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Analysis 1.6

Comparison 1 Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications), Outcome 6 Number of participants with ≥ 1 adverse event ‐ week 4.

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Analysis 1.7

Comparison 1 Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications), Outcome 7 Withdrawal due to adverse event ‐ week 4.

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Analysis 2.1

Comparison 2 Ivermectin 200 μg/kg (1 to 2 doses) versus permethrin 5% lotion (1 to 5 applications), Outcome 1 Complete clearance ‐ week 1.

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Analysis 2.2

Comparison 2 Ivermectin 200 μg/kg (1 to 2 doses) versus permethrin 5% lotion (1 to 5 applications), Outcome 2 Complete clearance ‐ week 2.

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Analysis 2.3

Comparison 2 Ivermectin 200 μg/kg (1 to 2 doses) versus permethrin 5% lotion (1 to 5 applications), Outcome 3 Number of participants with ≥ 1 adverse event ‐ week 2.

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Analysis 2.4

Comparison 2 Ivermectin 200 μg/kg (1 to 2 doses) versus permethrin 5% lotion (1 to 5 applications), Outcome 4 Withdrawal due to adverse event ‐ week 2.

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Analysis 3.1

Comparison 3 Ivermectin 200 μg/kg (1 to 3 doses) versus ivermectin 1% lotion/solution (1 to 3 applications), Outcome 1 Complete clearance ‐ week 1.

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Analysis 3.2

Comparison 3 Ivermectin 200 μg/kg (1 to 3 doses) versus ivermectin 1% lotion/solution (1 to 3 applications), Outcome 2 Complete clearance ‐ week 2.

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Analysis 3.3

Comparison 3 Ivermectin 200 μg/kg (1 to 3 doses) versus ivermectin 1% lotion/solution (1 to 3 applications), Outcome 3 Complete clearance ‐ week 4.

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Analysis 3.4

Comparison 3 Ivermectin 200 μg/kg (1 to 3 doses) versus ivermectin 1% lotion/solution (1 to 3 applications), Outcome 4 Number of participants with ≥ 1 adverse event ‐ week 4.

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Analysis 3.5

Comparison 3 Ivermectin 200 μg/kg (1 to 3 doses) versus ivermectin 1% lotion/solution (1 to 3 applications), Outcome 5 Withdrawal due to adverse event ‐ week 4.

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Analysis 4.1

Comparison 4 Ivermectin 1% lotion (1 to 3 applications) versus permethrin 5% cream (1 to 3 applications), Outcome 1 Complete clearance ‐ week 4.

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Analysis 4.2

Comparison 4 Ivermectin 1% lotion (1 to 3 applications) versus permethrin 5% cream (1 to 3 applications), Outcome 2 Number of participants with ≥ 1 adverse event ‐ week 4.

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Analysis 5.1

Comparison 5 Ivermectin 200 μg/kg (1 dose) versus ivermectin 200 μg/kg (2 doses), Outcome 1 Complete clearance ‐ week 4.

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Summary of findings for the main comparison. Oral ivermectin 200 μg/kg (1 to 3 doses) compared to topical permethrin 5% cream (1 to 3 applications)

Oral ivermectin 200 μg/kg (1 to 3 doses) compared to topical permethrin 5% cream (1 to 3 applications) for treating scabies
Patient or population: people with scabies, 2 to 80 years of age Location: India, Pakistan Intervention: oral ivermectin 200 μg/kg Comparison: topical permethrin 5% cream
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with permethrin 5% cream	Risk with ivermectin 200 μg/kg	Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
Complete clearance ‐ week 1	654 per 1000	425 per 1000 (353 to 510)	RR 0.65 (0.54 to 0.78)	613 (6 RCTs)¹	⊕⊕⊝⊝ LOW^2,3	‐
Complete clearance ‐ week 2	744 per 1000	677 per 1000 (565 to 804)	RR 0.91 (0.76 to 1.08)	459 (5 RCTs)⁴	⊕⊕⊝⊝ LOW^2,5	In 1 study non‐responders were re‐treated after 1 week; in 1 study 44.44% of participants (IVER) and 17.86% of participants (PER) were re‐treated after 1 week (absolute numbers are unclear).
Complete clearance ‐ week 4 ‐ IVER 1 dose versus PER 1 application	900 per 1000	900 per 1000 (774 to 1000)	RR 1.00 (0.86 to 1.16)	80 (1 RCT)⁶	⊕⊕⊕⊕ HIGH	‐
Complete clearance ‐ week 4 ‐ IVER 1 to 3 doses versus PER 1 to 3 applications	932 per 1000	857 per 1000 (764 to 959)	RR 0.92 (0.82 to 1.03)	581 (5 RCTs)⁷	⊕⊕⊝⊝ LOW^2,8	In 3 studies non‐responders were re‐treated once; in 1 study non‐responders were re‐treated after 2 and/or 3 weeks (absolute numbers are unclear); in 1 study 12 participants (IVER) and 1 participant (PER) were re‐treated after 2 weeks.
Complete clearance ‐ week 4 ‐ IVER 2 doses versus PER 1 application	900 per 1000	873 per 1000 (747 to 1000)	RR 0.97 (0.83 to 1.14)	80 (1 RCT)⁶	⊕⊕⊕⊕ HIGH	‐
Number of participants with ≥ 1 AE ‐ week 2	0 per 1000	0 per 1000 (0 to 0)	Not estimable	55 (1 RCT)⁹	⊕⊕⊕⊝ MODERATE²	0 events; 44.44% of participants (IVER) and 17.86% of participants (PER) were re‐treated after 1 week (absolute numbers are unclear)
Number of participants with ≥ 1 AE ‐ week 4	39 per 1000	51 per 1000 (14 to 190)	RR 1.30 (0.35 to 4.83)	502 (4 RCTs)¹⁰	⊕⊕⊝⊝ LOW^2,11	In 1 study non‐responders were re‐treated after 2 weeks; in 1 study non‐responders were re‐treated after 2 and 3 weeks; in 1 study participants in IVER group were re‐treated (absolute numbers are unclear).
Withdrawal due to AE ‐ week 4	See comment	See comment	‐	305 (3 RCTs)¹²	⊕⊕⊕⊝ MODERATE²	0 events; in 1 study non‐responders were re‐treated after 1 week (absolute numbers are unclear); in 1 study 12 participants (IVER) and 1 participant (PER) were re‐treated after 2 weeks
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations: AE: adverse event; CI: confidence interval; IVER: ivermectin; PER: permethrin; RCT: randomized controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
¹Usha 2000; Bachewar 2009; Sharma 2011; Rohatgi 2013; Meenakshi 2014; Wankhade 2016. ²Downgraded by 1 for serious risk of bias: assessed as moderate. ³Downgraded by 1 for serious imprecision: CI crosses minimal clinically important difference threshold: statistically significant difference of uncertain clinical importance. ⁴Usha 2000; Bachewar 2009; Mushtaq 2010; Sharma 2011; Rohatgi 2013. ⁵Downgraded by 1 for serious inconsistency: I² = 61% (P = 0.04). ⁶Sharma 2011. ⁷Usha 2000; Mushtaq 2010; Chhaiya 2012; Rohatgi 2013; Wankhade 2016. ⁸Downgraded by 1 for serious inconsistency: I² = 74% (P = 0.004). ⁹Bachewar 2009. ¹⁰Mushtaq 2010; Sharma 2011; Chhaiya 2012; Wankhade 2016. ¹¹Downgraded by 1 for serious imprecision: CI crosses line of no effect and minimal clinically important difference thresholds: uncertain whether there is any difference. ¹²Usha 2000; Manjhi 2014; Wankhade 2016.

Summary of findings for the main comparison. Oral ivermectin 200 μg/kg (1 to 3 doses) compared to topical permethrin 5% cream (1 to 3 applications)

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Summary of findings 2. Oral ivermectin 200 μg/kg (1 to 2 doses) compared to topical permethrin 5% lotion (1 to 5 applications)

Oral ivermectin 200 μg/kg (1 to 2 doses) compared to topical permethrin 5% lotion (1 to 5 applications) for treating scabies
Patient or population: people with scabies, 5 to 60 years of age Location: Egypt, Pakistan Intervention: oral ivermectin 200 μg/kg Comparison: topical permethrin 5% lotion
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with permethrin 5% lotion	Risk with ivermectin 200 μg/kg	Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
Complete clearance ‐ week 1 ‐ IVER 1 dose versus PER 1 application	733 per 1000	682 per 1000 (543 to 858)	RR 0.93 (0.74 to 1.17)	120 (1 RCT)¹	⊕⊕⊕⊝ MODERATE²	‐
Complete clearance ‐ week 1 ‐ IVER 1 dose versus PER on 5 consecutive nights	593 per 1000	415 per 1000 (279 to 610)	RR 0.70 (0.47 to 1.03)	107 (1 RCT)³	⊕⊕⊝⊝ LOW^2,4	‐
Complete clearance ‐ week 2 ‐ IVER 1 dose versus PER 1 application	667 per 1000	667 per 1000 (520 to 860)	RR 1.00 (0.78 to 1.29)	120 (1 RCT)¹	⊕⊕⊝⊝ LOW ^2,4	‐
Complete clearance ‐ week 2 ‐ IVER 2 doses versus PER on 5 consecutive nights	815 per 1000	790 per 1000 (660 to 953)	RR 0.97 (0.81 to 1.17)	107 (1 RCT)³	⊕⊕⊕⊝ MODERATE²	‐
Number of participants with ≥ 1 AE ‐ week 2 ‐ IVER 2 doses versus PER on 5 consecutive nights	0 per 1000	0 per 1000 (0 to 0)	RR 5.00 (0.25 to 101.58)	100 (1 RCT)¹	⊕⊝⊝⊝ VERY LOW ^2,5	‐
Withdrawal due to AE ‐ week 2 ‐ IVER 1 dose versus PER 1 application	0 per 1000	0 per 1000 (0 to 0)	Not estimable	120 (1 RCT)¹	⊕⊕⊕⊝ MODERATE²	0 events
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations: AE: adverse event; CI: confidence interval; IVER: ivermectin; PER: permethrin; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
¹Saqib 2012. ²Downgraded by 1 for serious risk of bias: assessed as moderate. ³Abdel‐Raheem 2016. ⁴Downgraded by 1 for serious imprecision: CI crosses line of no effect and minimal clinically important difference thresholds: uncertain whether there is any difference. ⁵Downgraded by 2 for very serious imprecision: CI crosses line of no effect and minimal clinically important difference thresholds: uncertain whether there is any difference and wide CI.

Summary of findings 2. Oral ivermectin 200 μg/kg (1 to 2 doses) compared to topical permethrin 5% lotion (1 to 5 applications)

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Summary of findings 3. Oral ivermectin 200 μg/kg (1 to 3 doses) compared to topical ivermectin 1% lotion/solution (1 to 3 applications)

Oral ivermectin 200 μg/kg (1 to 3 doses) compared to topical ivermectin 1% lotion/solution (1 to 3 applications) for treating scabies
Patient or population: people with scabies, 5 to 80 years of age Location: Egypt, India Intervention: oral ivermectin 200 μg/kg Comparison: topical ivermectin 1% lotion/solution
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with ivermectin 1% lotion/solution	Risk with ivermectin 200 μg/kg	Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
Complete clearance ‐ week 1	875 per 1000	735 per 1000 (569 to 945)	RR 0.84 (0.65 to 1.08)	62 (1 RCT)¹	⊕⊕⊝⊝ LOW^2,3	‐
Complete clearance ‐ week 2	1000 per 1000	1000 per 1000 (940 to 1000)	RR 1.00 (0.94 to 1.06)	62 (1 RCT)¹	⊕⊕⊕⊝ MODERATE²	8 participants (oral IVER) and 4 participants (topical IVER) were re‐treated after 1 week.
Complete clearance ‐ week 4	971 per 1000	961 per 1000 (922 to 1000)	RR 0.99 (0.95 to 1.03)	272 (2 RCTs)^1,4	⊕⊕⊕⊝ MODERATE²	In 1 study 8 participants (oral IVER) and 4 participants (topical IVER) were re‐treated after 1 week; in 1 study non‐responders were re‐treated after 2 and/or 3 weeks (absolute numbers are unclear).
Number of participants with ≥ 1 AE ‐ week 4	0 per 1000	0 per 1000 (0 to 0)	RR 5.05 (0.25 to 103.87)	201 (1 RCT)⁴	⊕⊝⊝⊝ VERY LOW^2,5	Non‐responders were re‐treated after 2 and/or 3 weeks (absolute numbers are unclear).
Withdrawal due to AE ‐ week 4	0 per 1000	0 per 1000 (0 to 0)	Not estimable	62 (1 RCT)⁴	⊕⊕⊕⊝ MODERATE²	0 events; 8 participants (oral IVER) and 4 participants (topical IVER) were re‐treated after 1 week.
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations: AE: adverse event; CI: confidence interval; IVER: ivermectin; RCT: randomized controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
¹Ahmad 2016. ²Downgraded by 1 for serious risk of bias: assessed as moderate. ³Downgraded by 1 for serious imprecision: CI crosses line of no effect and minimal clinically important difference thresholds: uncertain whether there is any difference. ⁴Chhaiya 2012. ⁵Downgraded by 2 for very serious imprecision: CI crosses line of no effect and minimal clinically important difference thresholds: uncertain whether there is any difference and wide CI.

Summary of findings 3. Oral ivermectin 200 μg/kg (1 to 3 doses) compared to topical ivermectin 1% lotion/solution (1 to 3 applications)

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Summary of findings 4. Topical ivermectin 1% lotion (1 to 3 applications) compared to topical permethrin 5% cream (1 to 3 applications)

Topical ivermectin 1% lotion (1 to 3 applications) compared to topical permethrin 5% cream (1 to 3 applications) for treating scabies
Patient or population: people with scabies, 5 to 80 years of age Location: India Intervention: topical ivermectin 1% lotion Comparison: topical permethrin 5% cream
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
	Risk with permethrin 5% cream	Risk with ivermectin 1% lotion
Complete clearance ‐ week 4	943 per 1000	962 per 1000 (905 to 1000)	RR 1.02 (0.96 to 1.08)	210 (1 RCT)¹	⊕⊕⊕⊝ MODERATE²	Non‐responders were re‐treated after 2 and/or 3 weeks (absolute numbers are unclear).
Number of participants with ≥ 1 AE ‐ week 4	10 per 1000	3 per 1000 (0 to 80)	RR 0.33 (0.01 to 7.93)	200 (1 RCT)¹	⊕⊝⊝⊝ VERY LOW^2,3	Non‐responders were re‐treated after 2 and/or 3 weeks (absolute numbers are unclear).
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations: AE: adverse event; CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
¹Chhaiya 2012. ²Downgraded by 1 for serious risk of bias: assessed as moderate. ³Downgraded by 2 for very serious imprecision: CI crosses line of no effect and minimal clinically important difference thresholds: uncertain whether there is any difference and wide CI.

Summary of findings 4. Topical ivermectin 1% lotion (1 to 3 applications) compared to topical permethrin 5% cream (1 to 3 applications)

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Summary of findings 5. Oral ivermectin 200 μg/kg (1 dose) compared to oral ivermectin 200 μg/kg (2 doses)

Oral ivermectin 200 μg/kg (1 dose) compared to oral ivermectin 200 μg/kg (2 doses) for treating scabies
Patient or population: people with scabies, over 5 years of age Location: India Intervention: oral ivermectin 200 μg/kg 1 dose Comparison: oral ivermectin 200 μg/kg 2 doses
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
	Risk with ivermectin 200 μg/kg 2 doses	Risk with ivermectin 200 μg/kg 1 dose
Complete clearance ‐ week 4	900 per 1000	873 per 1000 (747 to 1000)	RR 0.97 (0.83 to 1.14)	80 (1 RCT)¹	⊕⊕⊕⊕ HIGH	‐
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations: CI: confidence interval; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.
¹Sharma 2011.

Summary of findings 5. Oral ivermectin 200 μg/kg (1 dose) compared to oral ivermectin 200 μg/kg (2 doses)

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Comparison 1. Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Complete clearance ‐ week 1 Show forest plot	6	613	Risk Ratio (M‐H, Random, 95% CI)	0.65 [0.54, 0.78]

2 Complete clearance ‐ week 2 Show forest plot	5	459	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.76, 1.08]

3 Complete clearance ‐ week 4 Show forest plot	6		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 IVER 1 dose versus PER 1 application	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.86, 1.16]
3.2 IVER 1 to 3 doses versus PER 1 to 3 applications	5	581	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.82, 1.03]
3.3 IVER 2 doses versus PER 1 application	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.83, 1.14]
4 Subgroup analysis for 1.3.2 ‐ complete clearance ‐ week 4 Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 IVER 1 to 3 doses versus PER 1 to 3 applications ‐ 5 studies	5	581	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.82, 1.03]
4.2 IVER 1 to 3 doses versus PER 1 to 3 applications ‐ 3 studies	3	410	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.91, 1.06]
5 Number of participants with ≥ 1 adverse event ‐ week 2 Show forest plot	1	55	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

6 Number of participants with ≥ 1 adverse event ‐ week 4 Show forest plot	4	502	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.35, 4.83]

7 Withdrawal due to adverse event ‐ week 4 Show forest plot	3	305	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. Ivermectin 200 μg/kg (1 to 3 doses) versus permethrin 5% cream (1 to 3 applications)

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Comparison 2. Ivermectin 200 μg/kg (1 to 2 doses) versus permethrin 5% lotion (1 to 5 applications)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Complete clearance ‐ week 1 Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 IVER 1 dose versus PER 1 application	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.74, 1.17]
1.2 IVER 1 dose versus PER on 5 consecutive nights	1	107	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.47, 1.03]
2 Complete clearance ‐ week 2 Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 IVER 1 dose versus PER 1 application	1	120	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.78, 1.29]
2.2 IVER 2 doses versus PER on 5 consecutive nights	1	107	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.81, 1.17]
3 Number of participants with ≥ 1 adverse event ‐ week 2 Show forest plot	1	100	Risk Ratio (M‐H, Random, 95% CI)	5.00 [0.25, 101.58]

4 Withdrawal due to adverse event ‐ week 2 Show forest plot	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Ivermectin 200 μg/kg (1 to 2 doses) versus permethrin 5% lotion (1 to 5 applications)

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Comparison 3. Ivermectin 200 μg/kg (1 to 3 doses) versus ivermectin 1% lotion/solution (1 to 3 applications)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Complete clearance ‐ week 1 Show forest plot	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.65, 1.08]

2 Complete clearance ‐ week 2 Show forest plot	1	62	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.94, 1.06]

3 Complete clearance ‐ week 4 Show forest plot	2	272	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.95, 1.03]

4 Number of participants with ≥ 1 adverse event ‐ week 4 Show forest plot	1	201	Risk Ratio (M‐H, Random, 95% CI)	5.05 [0.25, 103.87]

5 Withdrawal due to adverse event ‐ week 4 Show forest plot	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 3. Ivermectin 200 μg/kg (1 to 3 doses) versus ivermectin 1% lotion/solution (1 to 3 applications)

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Comparison 4. Ivermectin 1% lotion (1 to 3 applications) versus permethrin 5% cream (1 to 3 applications)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Complete clearance ‐ week 4 Show forest plot	1	210	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.96, 1.08]

2 Number of participants with ≥ 1 adverse event ‐ week 4 Show forest plot	1	200	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 7.93]

Comparison 4. Ivermectin 1% lotion (1 to 3 applications) versus permethrin 5% cream (1 to 3 applications)

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Comparison 5. Ivermectin 200 μg/kg (1 dose) versus ivermectin 200 μg/kg (2 doses)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Complete clearance ‐ week 4 Show forest plot	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.83, 1.14]

Comparison 5. Ivermectin 200 μg/kg (1 dose) versus ivermectin 200 μg/kg (2 doses)

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