Ivermectin and permethrin for treating scabies

Stefanie Rosumeck; Alexander Nast; Corinna Dressler

doi:10.1002/14651858.CD012994

ایورمکتین و پرمترین در درمان گال

Appendices

Appendix 1. Search strategy

Search set	CIDG SR^a/ EconLit/ ERIC	CENTRAL	MEDLINE/Embase^b	LILACS^b	IndMED
1	scabies	scabies ti, ab	scabies ti, ab	scabies	scabies
2	—	"scabies" [MeSH]	"scabies" [MeSH/Emtree]	permethrin	sarcoptes scabiei
3	—	"sarcoptes scabiei" [MeSH]	"sarcoptes scabiei" [MeSH/Emtree]	ivermectin	1 or 2
4	—	1 or 2 or 3	1 or 2 or 3	2 or 3	—
5	—	permethrin ti, ab	permethrin ti, ab	1 and 4	—
6	—	"permethrin" [MeSH]	"permethrin" [MeSH/Emtree]	—	—
7	—	"pyrethrins" [MeSH]	"pyrethrins" [MeSH]	—	—
8	—	ivermectin ti, ab	"pyrethroid" [Emtree]	—	—
9	—	"ivermectin" [MeSH]	ivermectin ti, ab	—	—
10	—	5 or 6 or 7 or 8 or 9	"ivermectin" [MeSH/Emtree]	—	—
11	—	4 and 10	5 or 6 or 7 or 8 or 9 or 10	—	—
12	—	—	4 and 11	—	—

^aCochrane Infectious Diseases Group Specialized Register.
^bSearch terms used in combination with the search strategy for retrieving trials developed by the Cochrane Collaboration (Lefebvre 2011).

Appendix 2. Sensitivity analyses: summary table

Comparison

Subgroup

Outcome

Sensitivity analysis

Meta‐analysis

Ivermectin 200 μg/kg versus permethrin 5% cream

—

Complete clearance ‐ week 2

Without Usha 2000 (significant effect estimate):

RR 0.96, 95% CI 0.88 to 1.06 (I² statistic = 0%)

Without Bachewar 2009; Rohatgi 2013 (some participants were re‐treated after 1 week):

RR 0.81, 95% CI 0.56 to 1.19 (I² statistic = 71%)

RR 0.91, 95% CI 0.76 to 1.08 (I² statistic = 61%)

IVER 1 to 3 doses versus PER 1 to 3 doses

Complete clearance ‐ week 4

Without Usha 2000 (significant effect estimate):

RR 0.97, 95% CI 0.91 to 1.05 (I² statistic = 31%)

Without Usha 2000; Mushtaq 2010 (non‐responders re‐treated after 2 weeks):

RR 0.98, 95% CI 0.91 to 1.06 (I² statistic = 36%)

RR 0.92, 95% CI 0.82 to 1.03 (I² statistic = 74%)

Abbreviations: CI: confidence interval; IVER: ivermectin; PER: permethrin; RR: risk ratio.

Appendix 3. Number of participants re‐treated

Study	Initial treatment	Follow‐up week 1	Follow‐up week 2	Follow‐up week 3	Follow‐up week 4
Studies that treated participants once
Manjhi 2014	1 x IVER 200 µg/kg	‐	‐	‐	‐
Manjhi 2014	1 x PER 5%	‐	‐	‐	‐
Saqib 2012	1 x IVER 200 µg/kg	‐	‐	‐	‐
Saqib 2012	1 x PER 5%	‐	‐	‐	‐
Studies that treated participants once and re‐treated only non‐responders
Ahmad 2016	1 x IVER 1%	Yes, 4/32 participants	‐	‐	‐
Ahmad 2016	1 x IVER 200 µg/kg	Yes, 8/30 participants	‐	‐	‐
Bachewar 2009	1 x IVER 200 µg/kg	Yes, 44.44% of participants	‐	‐	‐
Bachewar 2009	1 x PER 5%	Yes, 17.86% of participants	‐	‐	‐
Chhaiya 2012	1 x IVER 200 µg/kg	Yes, n unclear	Yes, n unclear	Switch over to PER 5%	‐
	1 x IVER 1%	Yes, n unclear	Yes, n unclear	Switch over to PER 5%	‐
	1 x PER 5%	Yes, n unclear	Yes, n unclear	Yes, n unclear	‐
Mushtaq 2010	1 x IVER 200 µg/kg	‐	Yes, n unclear	‐	‐
Mushtaq 2010	1 x PER 5%	‐	Yes, n unclear	‐	‐
Rohatgi 2013	1 x IVER 200 µg/kg	Yes, n unclear	‐	‐	‐
Rohatgi 2013	1 x PER 5%	Yes, n unclear	‐	‐	‐
Usha 2000	1 x IVER 200 µg/kg	‐	Yes, 12 participants	‐	Cross‐over if treatment failure
Usha 2000	1 x PER 5%	‐	Yes, 1 participant	‐	Cross‐over if treatment failure
Wankhade 2013	1 x IVER 200 µg/kg	Yes, n unclear	‐	‐	‐
Wankhade 2013	1 x PER 5%	Yes, n unclear	‐	‐	‐
Wankhade 2016	1 x IVER 200 µg/kg	Yes, n unclear	‐	‐	‐
Wankhade 2016	1 x PER 5%	Yes, n unclear	‐	‐	‐
Studies that treated all participants with more than 1 dose
Abdel‐Raheem 2016	1 x IVER 200 µg/kg	1 x IVER 200 µg/kg	Yes, time and n unclear
Abdel‐Raheem 2016	PER 5% for 5 consecutive nights	‐
Das 2006	1 x IVER 200 µg/kg	‐	1 x IVER 200 µg/kg	‐	‐
Das 2006	1 x PER 5%	‐	‐	‐	‐
Macotela‐Ruiz 1996	1 x IVER 250 µg/kg	‐	‐	‐	‐
Macotela‐Ruiz 1996	1 x IVER 250 µg/kg	Day 3: 1 x IVER 250 µg/kg	Day 10: 1 x IVER 250 µg/kg	‐	‐
Meenakshi 2014	1 x IVER 200 µg/kg	1 x IVER 200 µg/kg	‐	‐	‐
Meenakshi 2014	1 x PER 5%	1 x PER 5%	‐	‐	‐
Sharma 2011	1 x IVER 200 µg/kg	‐	‐	‐	‐
	1 x IVER 200 µg/kg	‐	Day 15: 1 x IVER 200 µg/kg	‐	‐
	1 x PER 5%	‐	‐	‐	‐

Abbreviations: IVER: ivermectin; PER: permethrin.

Appendix 4. Definition and diagnosis of complete clearance

Study	Name of outcome	Definition and evaluation
Abdel‐Raheem 2016	Complete cure	Negative parasitological examination with complete absence of new lesions residual and all new lesions were scraped for detection of mites if only one mite was detected, this was considered as treatment failure
Ahmad 2016	Cure	Clinical assessment by 1 researcher 4‐point scale for lesion count: 0 = no skin lesions; 1 = ≤ 10 lesions; 2 = 11 to 49 lesions; 3 ≥ 50 lesions) 4‐point scale for pruritus: 0 = no pruritus; 1 = mild pruritus; 2 = moderate pruritus; 3 = marked pruritus cure = 0 laboratory diagnosis: demonstration of mites and/or mite products (eggs, larva, or faecal pellets) in scrapings from skin lesions (burrows or scabetic papules from classical sites: finger webs, flexural aspect of wrist, or penile shaft) using light microscopy after incubation in 15% potassium hydroxide
Bachewar 2009	Cure	No new lesions papules, vesicles, and classical burrows examined by dermatologist and principal investigator to standardize clinical evaluation
Chhaiya 2012	Clinical cure of scabietic lesions	No definition
Das 2006	Improvement clinically	No definition
Macotela‐Ruiz 1996	Cure	Considerable improvement of dermatosis, no pruritus, no new lesions
Manjhi 2014	Complete improvement	Based on severity of pruritus or lesions lesion count: < 10: mild, 11 to 49: moderate, > 50: severe pruritus on 10‐centimetre visual analogue scale: 0 ‐ no pruritus, 1 to 3 ‐ mild, 4 to 6 ‐ moderate, 7 to 10 ‐ severe complete improvement not defined
Meenakshi 2014	Complete clinical cure	Reduction in clinical grading score up to grade 0 or 1 and reduction in itching grading score up to grade 0, 1, or 2; "moderate or good improvement" clinical grading score: 0 = free of lesions (no lesions), 1 = 10 or fewer lesions (mild), 2 = 11 to 49 lesions (moderate), 3 = 50 or more lesions (severe) itching grading score: participant was asked for reduction in pruritus, grading was done on given scale by the observer: 0 = 0% (no pruritus), 1 = 1% to 25% (mild pruritus), 2 = 26% to 50% (moderate pruritus), 3 = 51% to 75% (severe pruritus), 4 = 76% to 100% (very severe pruritus)
Mushtaq 2010	Cure of disease	No lesions
Rohatgi 2013	Cure	Absence of clinical lesions and no new lesions like papules, vesicles, and classical burrows suggestive of live parasite
Saqib 2012	Cure	No itching, cutaneous lesions/burrows, and negative microscopy
Sharma 2011	Complete clinical cure	Reduction in both the number of lesions and the grade of pruritus by more than or equal to 50% (that is, moderate and good improvement) and negative microscopy
Usha 2000	Complete clearance	Good improvement
Wankhade 2013	Cure rate	No definition
Wankhade 2016	Cure	No new clinical lesions and improvement in pruritus, no new lesions like papules, vesicles, and classical burrows suggestive of live parasite seen

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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Appendices

Appendix 1. Search strategy

Appendix 2. Sensitivity analyses: summary table

Appendix 3. Number of participants re‐treated

Appendix 4. Definition and diagnosis of complete clearance

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Appendices

Appendix 1. Search strategy

Appendix 2. Sensitivity analyses: summary table

Appendix 3. Number of participants re‐treated

Appendix 4. Definition and diagnosis of complete clearance

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