FINAL Management options for moderate to severe acne – pairwise comparisons

Evidence tables for review question: What is the effectiveness and acceptability of interventions for the treatment of moderate to severe acne (side effects and participant reported improvement)?

Table 4: Evidence table Study details Participants Interventions Outcomes and results Comments Study details N=66 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Mucosal or cutaneous Tool v2.0 Akman, A. D., C.,Senturk, Sex (weeks) changes (n/N): arm 1 1. Randomisation M.,Koc, C. K.,Soyturk, mixed 26 16/22 Some concerns;no D.,Alpsoy, E.Treatment of acne age (mean±SD) Treatment duration Mucosal or cutaneous information with intermittent and 20.97±6.02 category changes (n/N): arm 2 provided conventional isotretinoin: A Inclusion/exclusion criteria 24+ weeks 18/19 2. Deviation from randomized, controlled Used validated acne scale Number of arms Mucosal or cutaneous intervention multicenter study. 2007. no 3 changes (n/N): arm 3 Some concerns;no Archives of Dermatological information Acne scale Split face design 19/19 Research provided; no ITT US FDA No Relapse follow up: arm Trial ID was done Inclusion details Intervention: arm 1 1 Akman 2007 3. Missing Participants with FDA global grade 2 ISO<120.Other=0.5 (first 52 weeks Country outcome data (moderate) and 3 to 4 (severe) acne who had 10 days, every month) Relapse follow up: arm Turkey (efficacy) not responded to conventional antibiotic Intervention: arm 2 2 High;10% Study type treatment or had rapidly relapsed after ISO<120.Other=0.5 52 weeks withdrawals / loss RCT conventional treatment. (every day for month 1 Relapse follow up: arm to follow-up - Source of funding then first 10 days of 3 balanced between Supported by Akdeni every month) 52 weeks arms; no ITT; University Scientific Research Participants receiving any conventional Intervention: arm 3 Relapse (n/N): arm 1 unclear reasons for Projects Unit. treatments underwent an appropriate washout ISO<120.Daily=0.5 3/22 wihdrawal Analysis method period before study treatment began. Coded intervention: Relapse (n/N): arm 2 4. Outcome Intention to treat or Exclusion details arm 1 0/19 measurement completers analysis Participants who had acne conglobata, acne ISO<120.Other=0.5-oral Relapse (n/N): arm 3 (efficacy) completers fulminans or systemic disorders requiring any Coded intervention: 0/19 Some concerns;not treatment. arm 2 reported if

ISO<120.Other=0.5-oral assessment of

outcome was

blinded

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Study details Participants Interventions Outcomes and results Comments Number included Coded intervention: 5. Selective Number randomised: arm 1 arm 3 reporting 22 ISO<120.Daily=0.5-oral Some concerns;not Number randomised: arm 2 Treatment category reported if trial protocol was 22 Oral isotretinoin Number randomised: arm 3 registered 22 6. Overall bias Number completed: arm 1 High 22 Number completed: arm 2 19 Number completed: arm 3 19 Study details N=134 Interventions Results Cochrane RoB Reference Characteristics Treatment duration GI side effects (n/N): Tool v2.0 Bossuyt, L. B., J.,Richert, Sex (weeks) arm 1 1. Randomisation B.,Cromphaut, P.,Mitchell, mixed 12 3/56 Some concerns;no T.,Al Abadie, M.,Henry, age (mean±SD) Treatment duration GI side effects (n/N): information I.,Bewley, A.,Poyner, T.,Mann, 18.6 category arm 2 provided N.,Czernielewski, age (min/max) 12 to <24 weeks 2/53 2. Deviation from J.Lymecycline in the treatment 12/29 Number of arms Participant reported intervention of acne: An efficacious, safe Some concerns;not age (other information) 2 improvement (n/N): arm and cost-effective alternative to reported if LYME mean age 18.6 (range 13 - 29), MINO Split face design 1 minocycline. 2003. European participants were mean age 18.6 (range 12 - 29) No 53/66 Journal of Dermatology blinded; ITT Intervention: arm 1 Patient reported Trial ID Inclusion/exclusion criteria analysis was done; LYME-oral 300mg improvement (n/N): arm Bossuyt 2003 Used validated acne scale 8% protocol no Intervention: arm 2 2 Country deviations in LYME MINO-oral 100mg 53/68 Europe Acne scale arm vs 1.5% in Leeds Grading Scale, Cunliffe Coded intervention: Study type MINO arm arm 1 RCT Inclusion details 3. Missing Males or females aged between 12 and 30 LYME-oral Source of funding outcome data years. Participants with at least 15 and at most Coded intervention: Galderma Belgilux N.V./S.A. (efficacy) 120 inflammatory facial lesions (papules, arm 2 and Galderma UK Limited. Some pustules, nodules) including at most 2 facial MINO-oral concerns;22% Analysis method nodules (diameter >1 cm), a maximum of 60 Treatment category withdrawals / loss Intention to treat or non-inflammatory facial lesions (open and Oral antibiotics to follow-up -

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Study details Participants Interventions Outcomes and results Comments completers analysis closed comedones) and an acne severity balanced between ITT grade between 1 and 5 (Leeds grading scale). arms; 1.5% due to Method of ITT imputation Women of childbearing age were required to lack of efficacy; use contraception during the study and for 1 ITT used; LOCF month after completing the trial. Women on 4. Outcome oral contraceptives were to have been using measurement the same method for 3 months prior to (efficacy) enrolment, or for at least 12 months for Low;investigator- contraceptive pills constraining cyproterone masked acetate. Use of cosmetics was permitted 5. Selective during the course of the study, but reporting contraceptives and cosmetics had to be listed Some concerns;not as concomitant medication. reported if trial Exclusion details protocol was Pregnancy or lactating women..Participants registered with acne conglobata, acne fulminans or 6. Overall bias secondary acne..Participants using topical Some concerns anti-acne or anti-inflammatory drugs or antibiotics, with the exception of short-courses of penicillin during the previous 6 months. Number included Number randomised: arm 1 66 Number randomised: arm 2 68 Number completed: arm 1 52 Number completed: arm 2 52 Study details N=87 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Participant reported Tool v2.0 Braathen, L. R.Topical Sex (weeks) improvement (n/N): arm 1. Randomisation clindamycin versus oral mixed 8 1 Some concerns;no tetracycline and placebo in age (mean±SD) Treatment duration 22/29 information acne vulgaris. 1984. 20 category Patient reported provided Scandinavian Journal of age (min/max) 6 to <12 weeks improvement (n/N): arm 2. Deviation from Infectious Diseases 16/35 intervention

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Study details Participants Interventions Outcomes and results Comments Trial ID Inclusion/exclusion criteria Number of arms 2 Some Braathen 1984 Used validated acne scale 3 21/29 concerns;double- Country no Split face design Participant reported blinded but not Norway Acne scale No improvement (n/N): arm clear who was blinded; no ITT Study type None Intervention: arm 1 3 analysis RCT Inclusion details CLIND-topical 1% + PLC- 1/29 Source of funding Participants with moderate to severe acne oral 3. Missing Not reported. vulgaris. Intervention: arm 2 outcome data TETRA-oral 500mg bid + (efficacy) Analysis method High;12% excluded Intention to treat or Vehicle from analysis for completers analysis Intervention: arm 3 unclear reasons - Exclusion details completers PLC-oral + Vehicle not clear if Participants with a history of gastrointestinal Coded intervention: disease..Participants who had received balanced between arm 1 arms; no ITT systemic or topical antibiotics, systemic or CLIND-topical + PLC-oral topical steroids, or androgenic drugs within 30 4. Outcome Coded intervention: days of entering the study. measurement arm 2 (efficacy) TETRA-oral + Vehicle Some concerns;not .Females who were pregnant, or had been on Coded intervention: reported if oral contraceptives for less than 3 months, or arm 3 assessment of had changed oral contraceptive within the PLC-oral + Vehicle outcome was previous 3 months. Treatment category blinded Number included Topical non-retinoids ± 5. Selective Number randomised: arm 1 other treatment reporting na Some concerns;not reported if trial Number randomised: arm 2 protocol was na registered Number randomised: arm 3 6. Overall bias na High Number completed: arm 1 29 Number completed: arm 2 29 Number completed: arm 3 29

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Study details Participants Interventions Outcomes and results Comments Study details N=50 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Chen, X. S., H.,Chen, Sex (weeks) arm 1 1. Randomisation S.,Zhang, J.,Niu, G.,Liu, mixed 3 7/24 Some concerns;no X.Clinical efficacy of 5- age (min/max) Treatment duration Skin irritation (n/N): information aminolevulinic acid 18/33 category arm 2 provided photodynamic therapy in the age (other information) 0 to <6 weeks 2/23 2. Deviation from treatment of moderate to ALA-PDT mean age=23.57; control=24.12 Treatment intensity intervention severe facial acne vulgaris. Some concerns;no Inclusion/exclusion criteria Total 4 sessions, once 2015. Experimental and information Used validated acne scale every week Therapeutic Medicine provided; not no Number of arms Trial ID 2 reported if ITT Chen 2015 Acne scale analysis was done None Split face design Country No 3. Missing China Inclusion details outcome data Participants with moderate (acne with Intervention: arm 1 Study type (efficacy) inflammatory papules and pustules) to severe 5ALA 5% photodynamic RCT Low;1 participant (acne with inflammatory papules, nodules, therapy Source of funding withdrew for cysts and scars) facial acne vulgaris. Intervention: arm 2 unreported reason Not reported. Sham treatment Exclusion details 4. Outcome Analysis method Use of topical antibiotics within 2 weeks of the Coded intervention: Intention to treat or measurement study or intake of systemic oral antibiotics arm 1 (efficacy) completers analysis within 4 weeks of the study.Use of systemic 5ALA-RED-PDT completers Some concerns;not retinoids within 6 months of the Coded intervention: reported if study..Porphyria or facial atopic arm 2 assessment of dermatitis..Pregnancy or lactation..History of PLC-physical outcome was keloid or photosensitivity Treatment category blinded disorders..Photosensitive eczema or Energy based (light / 5. Selective autoimmune diseases..Use of anti-acne laser) reporting medication such as prophylactics, Some concerns;not glucocorticoid and photosensitisers. reported if trial Number included protocol was Number randomised: arm 1 registered 25 6. Overall bias Number randomised: arm 2 Some concerns 25 Number completed: arm 1 24

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Study details Participants Interventions Outcomes and results Comments Number completed: arm 2 23 Study details N=105 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Participant reported Tool v2.0 Degreef, H. V., B. G.Double- Sex (weeks) improvement (n/N): arm 1. Randomisation blind evaluation of miconazole- mixed 12 1 Some concerns;no benzoyl peroxide combination age group Treatment duration 45/51 information for the topical treatment of =25 years category Patient reported provided acne vulgaris. 1982b. age (median) 12 to <24 weeks improvement (n/N): arm 2. Deviation from Dermatologica 15 Number of arms 2 intervention Trial ID 27/51 Low;double- age (min/max) 2 Degreef 1982b blinded; it looks 12/24 Split face design Country No like participants Inclusion/exclusion criteria were blinded; no Belgium Intervention: arm 1 Used validated acne scale ITT analysis Study type no BPO 5%/MICO 2% RCT cream 3. Missing Acne scale outcome data Source of funding Intervention: arm 2 Unknown, 5-point scale (efficacy) Not reported. BPO 5% cream Inclusion details Low;less than 5% Analysis method Participants with moderate to severe facial Coded intervention: withdrawals - Intention to treat or acne. arm 1 balanced between completers analysis Exclusion details BPO-topical + MICO- arms completers topical Not reported. 4. Outcome Number included Coded intervention: measurement Number randomised: arm 1 arm 2 (efficacy) 52 BPO-topical Some concerns;not Number randomised: arm 2 Treatment category reported if 53 Topical or combination assessment of Number completed: arm 1 outcome was 51 blinded Number completed: arm 2 5. Selective 51 reporting Some concerns;not reported if trial protocol was registered

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Study details Participants Interventions Outcomes and results Comments 6. Overall bias Some concerns Study details N=71 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Del Rosso, J. Q.Truncal acne Sex (weeks) arm 1 1. Randomisation vulgaris: the relative roles of mixed 10 3/32 Some concerns;no topical and systemic antibiotic age (mean±SD) Treatment duration Skin irritation (n/N): information therapy. 2007. Journal of drugs 18 category arm 2 provided in dermatology age (min/max) 6 to <12 weeks 2/28 2. Deviation from Trial ID 16/32 Number of arms GI side effects (n/N): intervention Del Rosso 2007 Some concerns;no Inclusion/exclusion criteria 2 arm 1 information Country Used validated acne scale Split face design 1/33 provided; no ITT United States no No GI side effects (n/N): analysis Study type Acne scale Intervention: arm 1 arm 2 3. Missing RCT None BPO 9% cleanser + 5/33 outcome data Source of funding Inclusion details CLIND 1% foam + DOXY Not reported. 100 mg (efficacy) Participants aged 16 years of age or High;15% Analysis method Intervention: arm 2 older..Acne vulgaris, truncal involvement on withdrawals (half Intention to treat or BPO 9% cleanser + the back with or without chest involvement, possibly due to completers analysis DOXY 100 mg truncal inflammatory acne severity graded as inefficiacy) - completers moderate or severe..Informed consent Coded intervention: imbalanced obtained..Undergone a washout period of at arm 1 between arms least 2 weeks for all previous topical acne BPO-topical + CLIND- (more in group 2); treatments (including over-the-counter topical + DOXY-oral no ITT products), at least 4 weeks for systemic Coded intervention: 4. Outcome antibiotic treatment, and more than 6 months arm 2 measurement for oral isotretinoin. BPO-topical + DOXY-oral (efficacy) Exclusion details Low Participants with concurrent intake or use 5. Selective within 4 weeks of baseline of systemic anti- reporting inflammatory medication that may influence Some concerns;not study outcomes (for example, systemic reported if trial corticosteroids), concurrent application or use protocol was within 2 weeks of baseline of topical anti- registered inflammatory medication (for example, corticosteroids or calcineurin 6. Overall bias inhibitors)..History of sensitivity or intolerance High

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Study details Participants Interventions Outcomes and results Comments associated with use of components of medications or products used in the study..Presence of a concurrent medical condition that the study investigator deems may potentially interfere with the study outcomes or participant assessments. Number included Number randomised: arm 1 36 Number randomised: arm 2 35 Number completed: arm 1 32 Number completed: arm 2 28 Study details N=240 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Mucosal or cutaneous Tool v2.0 Dhaked, D. R. M., R. Sex (weeks) changes (n/N): arm 1 1. Randomisation S.,Maheshwari, A.,Agarwal, U. mixed 24 115/118 Some concerns;no S.,Purohit, S.A randomized age (mean±SD) Treatment duration Mucosal or cutaneous information comparative trial of two low- 18.88±2.46 category changes (n/N): arm 2 provided dose oral isotretinoin regimens age (median) 24+ weeks 111/116 2. Deviation from in moderate to severe acne 18.51 Number of arms Relapse follow up: arm intervention vulgaris. 2016. Indian Some concerns;no age (min/max) 2 1 Dermatology Online Journal information 15/30 Split face design 12 Trial ID No Relapse follow up: arm provided; no ITT Dhaked 2016 Inclusion/exclusion criteria analysis Used validated acne scale Intervention: arm 1 2 Country 3. Missing no ISO<120.Daily<0.5 12 India outcome data Acne scale Intervention: arm 2 Relapse (n/N): arm 1 Study type (efficacy) Pochi ISO<120.Alt<0.5 0/118 RCT Low;2.5% Inclusion details Coded intervention: Relapse (n/N): arm 2 Source of funding withdrawals / lost Participants with moderate to severe acne arm 1 0/116 None (no conflicts of interest). to follow-up - vulgaris attending the outpatient clinic in the ISO<120.Daily<0.5-oral balanced between Analysis method dermatology department. Coded intervention: arms Intention to treat or arm 2 completers analysis 4. Outcome ISO<120.Alt<0.5-oral measurement completers

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Study details Participants Interventions Outcomes and results Comments Exclusion details Treatment category (efficacy) Participants with a personal or family history of Oral isotretinoin Some concerns;not hyperlipidaemia or diabetes. reported if Number included assessment of Number randomised: arm 1 outcome was 120 blinded Number randomised: arm 2 5. Selective 120 reporting Some concerns;not Number completed: arm 1 reported if trial 118 protocol was Number completed: arm 2 registered 116 6. Overall bias Some concerns Study details N=40 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Dhawan, S. S. G., Sex (weeks) arm 1 1. Randomisation J.Clindamycin phosphate mixed 12 1 Some 1.2%-benzoyl peroxide (5% or age (mean±SD) Treatment duration Skin irritation (n/N): concerns;insufficie 2.5%) plus tazarotene cream 21.9±8.34 category arm 2 nt information 0.1% for the treatment of acne. provided on age (min/max) 12 to <24 weeks 0 2013. Cutis allocation 12.3/45.9 Number of arms Skin irritation (n/N): Trial ID concealment Inclusion/exclusion criteria 2 arm 1 Dhawan 2013 2. Deviation from Used validated acne scale Split face design 20 intervention Country no No Skin irritation (n/N): Low;likely United States Intervention: arm 1 arm 2 Acne scale participants were Study type BPO 5%/CLIND 1.2% gel 20 Investigator's Static Global Assessment blinded; ITT RCT + TAZ 0.1% cream (ISGA)/Investigator's global severity analysis was done Source of funding Assessment Intervention: arm 2 3. Missing Stiefel, a GlaxoSmithKline BPO 2.5%/CLIND 1.2% Inclusion details outcome data company (conflicts of interest Males and females aged 12 to 45 gel + TAZ 0.1% cream reported). (efficacy) years..Participants with grade 3 or higher Coded intervention: Some Analysis method according to the investigator static global arm 1 concerns;12.5% Intention to treat or assessment (ISGA) (3=moderate; 4=severe; BPO-topical + CLIND- withdrawals/lost to completers analysis 5=very severe)..20 to 50 papules and pustules topical + TAZ-topical FU unclear ITT (inflammatory lesions), 30 to 100 open and Coded intervention: reasons - not clear closed comedones (non-inflammatory lesions), arm 2 if balanced

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Study details Participants Interventions Outcomes and results Comments Method of ITT imputation 1 or fewer small nodular lesions, no facial BPO-topical + CLIND- between arms; ITT not reported cystic lesions. topical + TAZ-topical done Exclusion details Treatment category 4. Outcome Topical or combination measurement Number included (efficacy) Number randomised: arm 1 Some concerns;not 20 reported if Number randomised: arm 2 assessment of 20 outcome was blinded Number completed: arm 1 na 5. Selective reporting Number completed: arm 2 Low na 6. Overall bias Some concerns Study details N=253 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Dobson, R. L. B., B. S.Topical Sex (weeks) arm 1 1. Randomisation erythromycin solution in acne. mixed 12 26 Some concerns;no Results of a multiclinic trial. age (other information) Treatment duration Skin irritation (n/N): information 1980. Journal of the American no age info reported category arm 2 provided Academy of Dermatology Inclusion/exclusion criteria 12 to <24 weeks 26 2. Deviation from Trial ID Used validated acne scale Number of arms Skin irritation (n/N): intervention Dobson 1980 no 2 arm 1 Some concerns;double- Country Acne scale Split face design 109 blinded but not United States None No Skin irritation (n/N): clear who was Study type Intervention: arm 1 arm 2 Inclusion details blinded; no ITT RCT ERYTH 1.5% solution 90 Participants with moderate to severe acne analysis Source of funding vulgaris of the face (at least 10 papules or Intervention: arm 2 3. Missing Not reported. pustules, one or more comedones, and not Vehicle outcome data Analysis method more than 5 nodulocystic lesions).. Coded intervention: (efficacy) Intention to treat or arm 1 High;21% completers analysis ERYTH-topical withdrawals - completers .No concurrent illness and not receiving any Coded intervention: imbalanced anti-acne treatment (topical or systemic) for at arm 2 between arms & least 2 weeks prior to study entry. Vehicle due to lack of efficacy (2 X more

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Study details Participants Interventions Outcomes and results Comments Exclusion details Treatment category in the vehicle arm); Not reported. Topical or combination no ITT Number included 4. Outcome Number randomised: arm 1 measurement 127 (efficacy) Number randomised: arm 2 Some 126 concerns;double- blinded but not Number completed: arm 1 clear who was 109 blinded Number completed: arm 2 5. Selective 90 reporting Some concerns;not reported if trial protocol was registered 6. Overall bias High Study details N=750 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Dogra, S., Sumathy, T. K., Sex (weeks) arm 1 1. Randomisation Nayak, C., Ravichandran, G., mixed 12 0 Some Vaidya, P. P., Mehta, S., Mittal, age (mean±SD) Treatment duration Skin irritation (n/N): concerns;random R., Mane, A., Charugulla, S. 21.2 category arm 2 allocation software N.Efficacy and safety used - but no age (median) 12 to <24 weeks 2 comparison of combination of further information 20 Number of arms Skin irritation (n/N): 0.04% tretinoin microspheres 3 arm 3 given plus 1% clindamycin versus age (min/max) Split face design 0 2. Deviation from their monotherapy in patients 12/48 No Skin irritation (n/N): intervention with acne vulgaris: a phase 3, Inclusion/exclusion criteria Low;double- Intervention: arm 1 arm 1 randomized, double-blind Used validated acne scale blinded but not Fixed dose tretinoin 300 study. 2020. Journal of no clear who was 0.04% (microsphere) + Skin irritation (n/N): Dermatological Treatment Acne scale blinded; ITT clindamycin 1.0% gel, arm 2 Trial ID Investigator's Static Global Assessment analysis was done o.d. 300 Dogra 2020 (ISGA)/Investigator's global severity 3. Missing Intervention: arm 2 Skin irritation (n/N): Country Assessment outcome data Tretinoin gel 0.025%, arm 3 India Inclusion details (efficacy) o.d. 150 Participants aged >/=12 years.Facial acne Some

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Study details Participants Interventions Outcomes and results Comments Study type (inflammatory lesion count [papulesþpustules] Intervention: arm 3 concerns;10% RCT count between >20 to <50; non-inflammatory Clindamycin gel 1.0%, discontinued in Source of funding lesion count [openþclosed comedones] o.d. total Dr. Reddy’s Laboratories Ltd, between >20 to <100, and nodules Coded intervention: 4. Outcome India. [inflammatory lesion 5mm in diameter] 2) and arm 1 measurement Investigator’s Static Global Assessment Analysis method TRET-topical+CLIND- (efficacy) (ISGA) score of 3 (moderate) or 4 (severe) Intention to treat or topical Some concerns;not completers analysis Exclusion details Coded intervention: reported if ITT Patients with a known allergy or sensitivity to arm 2 assessment of study drug, or who were concomitantly using outcome was Method of ITT imputation TRET-topical any potentially irritating over-the-counter blinded LOCF Coded intervention: products that contained benzoyl peroxide, a- arm 3 5. Selective hydroxy acids, salicylic acid, retinol or glycolic CLIND-topical reporting acids, or who required concurrent use of Low Treatment category topical (antimicrobials, anti-acne drugs, anti- 6. Overall bias Topical inflammatory agents, corticosteroids, retinoids) Some concerns or systemic (corticosteroids, antimicrobials, retinoids) medication and not willing to undergo the specified washout period Number included Number randomised: arm 1 300 Number randomised: arm 2 300 Number randomised: arm 3 150 Number completed: arm 1 277 Number completed: arm 2 267 Number completed: arm 3 133 Study details N=76 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Prevention of scarring Tool v2.0 Dréno, B., Tan, J., Rivier, M., Sex (weeks) reported as a mean % 1. Randomisation Martel, P., Bissonnette, R. mixed 26 increase from baseline Some concerns; no Adapalene 0.1%/benzoyl information

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Study details Participants Interventions Outcomes and results Comments peroxide 2.5% gel reduces the age (mean±SD) Treatment duration in scars: arm 1 provided on risk of atrophic scar formation 23.4 (3.6) category 4.5% allocation in moderate inflammatory age (median) 24+ weeks Prevention of scarring concealment acne: a split-face randomized 22 Number of arms reported as a mean % 2. Deviation from controlled trial. 2017. Journal age (min/max) 2 increase from baseline intervention of the European Academy of 19/32 Split face design in scars: arm 2 Some concerns; Dermatology and Venereology 24.8% participants not Inclusion/exclusion criteria Yes Trial ID blinded; ITT Used validated acne scale Intervention: arm 1 Dreno 2017 analysis was done No ADAP 0.1% gel + BPO Country Acne scale 2.5% gel. 3. Missing France/Canada outcome data No Intervention: arm 2 Study type (efficacy) Inclusion details Vehicle Split-face RCT Some concerns; Male and female participants aged 18–35 Coded intervention: 13% withdrawals Source of funding years with moderate facial acne vulgaris with arm 1 Funded by Galderma R&D 20–40 inflammatory lesions (papules and ADAP-topical + BPO- 4. Outcome Analysis method pustules, excluding the nose), no more than 1 topical measurement Intention to treat or acne nodule and a minimum of 10 atrophic (efficacy) Coded intervention: Low completers analysis acne scars (larger than 1.5mm in diameter, arm 2 5. Selective ITT smaller scars could not be accurately Vehicle Method of ITT imputation differentiated from other lesion types). reporting Treatment category Some concerns; Not reported Participants had no more than twice as many Topical lesions on one half of the face than on the additional

other half. outcomes were reported which Exclusion details were not in the trial Not reported protocol Number included 6. Overall bias Number randomised: arm 1 Some concerns 38 Number randomised: arm 2 38 Number completed: arm 1 33 Number completed: arm 2 33 Study details N=134 Interventions Results Cochrane RoB Reference Prevention of scarring Tool v2.0 reported as a mean %

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Study details Participants Interventions Outcomes and results Comments Dréno, B., Bissonnette, R., Characteristics Treatment duration decrease from baseline 1. Randomisation Gagné-Henley., A., Barankin, Sex (weeks) in scars: arm 1 Low B., Lynde, C., Kerrouche, N., mixed 24 15.5% 2. Deviation from Tan, J. Prevention and age (mean±SD) Treatment duration Prevention of scarring intervention Reduction of Atrophic Acne 21.5 (4.2) category reported as a mean % Some concerns; Scars with Adapalene Inclusion/exclusion criteria 24+ weeks ……. increase from baseline participants not 0.3%/Benzoyl Peroxide 2.5% in scars: arm 2 blinded; ITT Used validated acne scale Number of arms Gel in Subjects with Moderate no 14.4% analysis was done or Severe Facial Acne: Results 2 Acne scale 3. Missing of a 6-Month Randomized, Split face design Investigator Global Assessment (IGA) outcome data Vehicle-Controlled Trial Using Yes Inclusion details (efficacy) Intra-Individual Comparison. Intervention: arm 1 Some concerns; 2018. American Journal of Male or female participants aged 16–35 years ADAP 0.3% gel + BPO 19% withdrawals Clinical Dermatology with Fitzpatrick skin phototype I–IV and a clinical diagnosis of moderate or severe acne 2.5% gel 4. Outcome Trial ID vulgaris on the face. Participants had an Intervention: arm 2 measurement Dreno 2018 Investigator Global Assessment (IGA) Vehicle (efficacy) Country Low score of 3 or 4 on both sides; >=25 Coded intervention: France/Canada 5. Selective inflammatory lesions (papules and pustules) arm 1 Study type with 10 or more on each side (excluding reporting Split-face RCT ADAP-topical + BPO- Some concerns; the nose); up to two acne nodules >=1 cm for topical Source of funding additional whole face; 10 or more atrophic acne scars >2 Funded by Galderma Coded intervention: outcomes were mm (for whole face excluding the nose); with R&D/Nestle Skin arm 2 reported which an approximately symmetric number of Vehicle were not in the trial Health inflammatory and non-inflammatory lesions, protocol Analysis method and atrophic acne scars on the whole face. Treatment category Intention to treat or Topical 6. Overall bias Exclusion details Some concerns completers analysis Excluded were those ith acne conglobata, ITT acne fulminans, secondary acne, nodulocystic Method of ITT imputation acne, or acne requiring systemic treatment. LOCF Number included Number randomised: arm 1 67 Number randomised: arm 2 67 Number completed: arm 1 54

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Study details Participants Interventions Outcomes and results Comments Number completed: arm 2 54 Study details N=271 Interventions Results Cochrane RoB Reference Characteristics Treatment duration GI side effects (n/N): Tool v2.0 Dubertret, L. A., M.,Rostain, Sex (weeks) arm 1 1. Randomisation G.,Lahfa, M.,Forsea, mixed 12 4/111 Some concerns;no D.,Dimitrie Niculae, B.,Simola, age (min/max) Treatment duration GI side effects (n/N): information M.,Horvath, A.,Mizzi, F.The 14/39 category arm 2 provided use of lymecycline in the age (other information) 12 to <24 weeks 3/107 2. Deviation from treatment of moderate to mean age was 20.4, 21.2 & 20.5 yrs for LYME Number of arms GI side effects (n/N): intervention severe acne vulgaris: A 300mg, LYME 150mg and PLC groups 3 arm 3 Low;double- comparison of the efficacy and blinded; Inclusion/exclusion criteria Split face design 4/53 safety of two dosing regimens. participants likely Used validated acne scale No 2003. European Journal of blinded; ITT yes Intervention: arm 1 Dermatology analysis was done Acne scale LYME-oral 300mg od + Trial ID 3. Missing Leeds Revised Grading Scale PLC-oral Dubertret 2003 outcome data Intervention: arm 2 Country Inclusion details (efficacy) LYME-oral 150mg bid Europe Males and females aged between 16 and 40 Some years..Acne vulgaris with a minimum of 15 Intervention: arm 3 Study type concerns;12% inflammatory facial lesions and a global PLC-oral bid RCT withdrawals severity of at least grade 3 on the Leeds Coded intervention: Source of funding (unclear reasons) - Revised Acne Grading System. arm 1 Not reported. imbalanced Exclusion details LYME-oral + PLC-oral between arms Analysis method Coded intervention: (more in Intention to treat or Number included arm 2 lymecycline arm); completers analysis Number randomised: arm 1 LYME-oral ITT used ITT 111 Coded intervention: 4. Outcome Method of ITT imputation Number randomised: arm 2 arm 3 measurement LOCF 107 PLC-oral (efficacy) Number randomised: arm 3 Treatment category Some concerns;not reported if 53 Oral antibiotics Number completed: arm 1 assessment of outcome was 105 blinded Number completed: arm 2 88 5. Selective reporting Some concerns;not

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Study details Participants Interventions Outcomes and results Comments Number completed: arm 3 reported if trial 45 protocol was registered 6. Overall bias Some concerns Study details N=66 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Mucosal or cutaneous Tool v2.0 Faghihi, G. M., F.,Fard, N. Sex (weeks) changes (n/N): arm 1 1. Randomisation M.,Motamedi, N.,Hosseini, S. mixed 26 6/36 Some concerns;not M.Comparing the efficacy of age (mean±SD) Treatment duration Mucosal or cutaneous clear how low dose and conventional 23±5.54 category changes (n/N): arm 2 allocation dose of oral isotretinoin in sequence and Inclusion/exclusion criteria 24+ weeks 12/30 treatment of moderate and concealment were Used validated acne scale Number of arms New psychiactric severe acne vulgaris. 2017. done no 2 diagnosis (n/N): arm 1 Journal of Research in 2. Deviation from Acne scale Split face design 2/36 Pharmacy Practice intervention Global Acne Grading System (GAGS) No New psychiactric Trial ID Some concerns;not Intervention: arm 1 diagnosis (n/N): arm 2 Faghihi 2017 Inclusion details reported if ISO<120.Daily<0.5 + 2/30 Males and females with moderate to severe participants were Country PRED 0.25 mg wk 1 + Relapse follow up: arm acne vulgaris referred for treatment to Alzahra blinded; no ITT Iran, Islamic Republic of AZITH 250 mg wks 1-2 1 Medical and Training Centre, several clinical analysis was done Study type affiliated to Isfahan University of Medical Intervention: arm 2 26 3. Missing RCT Sciences and a privately-owned doctor's ISO<120.Daily=0.5 + Relapse follow up: arm outcome data Source of funding office..Consent to participate in the study..No PRED 0.25 mg wk 1 + 2 (efficacy) Isfahan University of Medical sensitivity to retinoids..No pregnancy, not AZITH 250 mg wks 1-2 26 Some concerns;not Sciences (no conflicts of willing to become pregnant, and absence of Coded intervention: reported how interest). hormonal disorders. arm 1 many/if participants Analysis method Exclusion details ISO<120.Daily<0.5-oral withdrew Intention to treat or Failure of participants to attend follow-up visits Coded intervention: 4. Outcome completers analysis for any reason..Adoption of other arm 2 measurement completers supplementary treatments during the study. ISO<120.Daily=0.5-oral (efficacy) Number included Treatment category Low Number randomised: arm 1 Oral isotretinoin 5. Selective 36 reporting Number randomised: arm 2 Low;looks like trial 30 protocol was Number completed: arm 1 registered but not 36 possible to access

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Study details Participants Interventions Outcomes and results Comments Number completed: arm 2 6. Overall bias 30 Some concerns Study details N=744 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Feldman, S. R. W., C. P.,Alio Sex (weeks) arm 1 1. Randomisation Saenz, A. B.The efficacy and mixed 12 66/371 Low tolerability of tazarotene foam, age (mean±SD) Treatment duration Skin irritation (n/N): 2. Deviation from 0.1%, in the treatment of acne 18.400269179004±6.0598000000000001 category arm 2 intervention vulgaris in 2 multicenter, age (min/max) 12 to <24 weeks 5/372 Low;double- randomized, vehicle-controlled, 12/44 Number of arms Light sensitivity (n/N): blinded; study double-blind studies. 2013. center, age (other information) 2 arm 1 Journal of Drugs in TAZ: 12-17, n=223, 18-25, n=104, 26-35, Split face design 2/371 Dermatology: JDD n=38, 36-45, n=6; VEH: 12-17, n=227, 18-25, No Light sensitivity (n/N): Trial ID study monitors, n=99, 26-35, n=33, 36-45, n=13 Intervention: arm 1 arm 2 Feldman 2013;Trial 1 sponsor personnel Inclusion/exclusion criteria TAZ 0.1% foam 0/372 Country were blinded to the Used validated acne scale Intervention: arm 2 North America treatment no Vehicle Study type assignments. ITT Acne scale Coded intervention: RCT analysis was done Investigator's Static Global Assessment arm 1 3. Missing Source of funding (ISGA)/Investigator's global severity TAZ-topical Stiefel, a GlaxoSmithKline outcome data Assessment Coded intervention: company (conflicts of interest (efficacy) Inclusion details arm 2 were reported). Some Males and females aged between 12 and 45 Vehicle concerns;14% Analysis method years, in good general health and agreed to Treatment category discontinued Intention to treat or use a medically-acceptable form of Topical retinoids (unclear how many completers analysis contraception throughout the study. due to inefficacy)- ITT Moderate to severe acne vulgaris: imbalanced Method of ITT imputation Investigator's Static Global Assessment between arms LOCF (ISGA) score =3 at baseline; lesion counts of (more in 25 to 50 facial inflammatory lesions (papules tazarotene foam plus pustules), including nasal lesions, with no arm) more than one facial nodular lesion (<5 mm) 4. Outcome and no cystic lesions, and 30 to 125 facial measurement non-inflammatory lesions (open and closed (efficacy) comedones), excluding nasal lesions..Provide Low consent.

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Study details Participants Interventions Outcomes and results Comments Exclusion details 5. Selective History of suspected intolerance to tazarotene reporting or any of the ingredients of the study Low products..Participants taking certain topical 6. Overall bias and systemic treatments were required to Some concerns undergo specified washout periods. Number included Number randomised: arm 1 372 Number randomised: arm 2 372 Number completed: arm 1 307 Number completed: arm 2 333 Study details N=742 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Feldman, S. R. W., C. P.,Alio Sex (weeks) arm 1 1. Randomisation Saenz, A. B.The efficacy and mixed 12 41/373 Low tolerability of tazarotene foam, age (mean±SD) Treatment duration Light sensitivity (n/N): 2. Deviation from 0.1%, in the treatment of acne 19.2±6.6463999999999999 category arm 1 intervention vulgaris in 2 multicenter, age (min/max) 12 to <24 weeks 1/373 Low;double- randomized, vehicle-controlled, 12/45 Number of arms blinded; study double-blind studies. 2013. center, age (other information) 2 Journal of Drugs in TAZ: 12-17, n=205, 18-25, n=117, 26-35, Split face design Dermatology: JDD n=35, 36-45, n=16; VEH: 12-17, n=205, 18-25, No Trial ID study monitors, n=108, 26-35, n=37, 36-45, n=19 Intervention: arm 1 Feldman 2013;Trial 2 sponsor personnel Inclusion/exclusion criteria TAZ 0.1% foam Country were blinded to the Used validated acne scale Intervention: arm 2 North America treatment no Vehicle Study type assignments. ITT Acne scale Coded intervention: RCT analysis was done Investigator's Static Global Assessment arm 1 3. Missing Source of funding (ISGA)/Investigator's global severity TAZ-topical Stiefel, a GlaxoSmithKline outcome data Assessment Coded intervention: company (conflicts of interest (efficacy) Inclusion details arm 2 were reported). Some Males and females aged between 12 and 45 Vehicle concerns;14% years, in good general health and agreed to

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Study details Participants Interventions Outcomes and results Comments Analysis method use a medically-acceptable form of Treatment category discontinued Intention to treat or contraception throughout the study. Topical retinoids (unclear how many completers analysis due to inefficacy)- ITT imbalanced Method of ITT imputation .Moderate to severe acne vulgaris: between arms Investigator's Static Global Assessment (more in LOCF (ISGA) score =3 at baseline; lesion counts of tazarotene foam 25 to 50 facial inflammatory lesions (papules arm) plus pustules), including nasal lesions, with no 4. Outcome more than one facial nodular lesion (<5 mm) measurement and no cystic lesions, and 30 to 125 facial (efficacy) non-inflammatory lesions (open and closed Low comedones), excluding nasal lesions..Provide 5. Selective consent. reporting Exclusion details Low History of suspected intolerance to tazarotene 6. Overall bias or any of the ingredients of the study Some concerns products..Participants taking certain topical and systemic treatments were required to undergo specified washout periods. Number included Number randomised: arm 1 373 Number randomised: arm 2 369 Number completed: arm 1 307 Number completed: arm 2 334 Study details N=73 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Breakthrough bleeding Tool v2.0 Fugere, P. P.-S., R. K.,Lussier- Sex (weeks) (n/N): arm 1 1. Randomisation Cacan, S.,Davignon, female 48 2/40 Some concerns;no J.,Farquhar, D.Cyproterone age (mean±SD) Treatment duration Breakthrough bleeding information acetate/ethinyl estradiol in the 22.9260273972603±3.2639999999999998 category (n/N): arm 2 provided treatment of acne. A age (min/max) 24+ weeks 4/33 2. Deviation from comparative dose-response 17/35 intervention study of the estrogen

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Study details Participants Interventions Outcomes and results Comments component. 1990. Inclusion/exclusion criteria Number of arms Low;double- Contraception Used validated acne scale 2 blinded - clear that Trial ID no Split face design participants were Fugere 1990 Acne scale No blinded; no ITT analysis Country Cook Intervention: arm 1 Canada Inclusion details CPA 2mg + EE 0.035 mg 3. Missing Study type Women in good health aged between 18 and (Diane-35) outcome data RCT 35 years..Moderate to severe androgen- Intervention: arm 2 (efficacy) High;23% Source of funding dependent acne vulgaris (defined as presence CPA 2mg + EE 0.05 mg withdrawals - not Not reported. of comedones, papules and macules on at (Diane-50) least half of the face..Previous treatment clear if balanced Analysis method Coded intervention: withdrawn within 6 weeks of starting study between arms; no Intention to treat or arm 1 treatments. ITT used completers analysis CPA-oral + EE-oral 4. Outcome completers Exclusion details Coded intervention: measurement Not reported. arm 2 Number included (efficacy) CPA-oral + EE-oral Some concerns;not Number randomised: arm 1 Treatment category reported if 40 Hormonal contraceptives assessment of Number randomised: arm 2 / Hormone-modifying outcome was 33 agents blinded Number completed: arm 1 5. Selective 37 reporting Number completed: arm 2 Some concerns;not 25 reported if trial protocol was registered 6. Overall bias High Study details N=225 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Participant reported Tool v2.0 Gratton, D. R., G. P.,Guertin- Sex (weeks) improvement (n/N): arm 1. Randomisation Larochelle, S.,Maddin, S. mixed 8 1 Some concerns;no W.,Leneck, C. M.,Warner, age (min/max) Treatment duration 92/105 information J.,Collins, J. P.,Gaudreau, 18/35 category Participant reported provided P.,Bendl, B. J.Topical 6 to <12 weeks improvement (n/N): arm 2. Deviation from clindamycin versus systemic 2 intervention tetracycline in the treatment of 56/97 Low;double-

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Study details Participants Interventions Outcomes and results Comments acne. Results of a multiclinic Inclusion/exclusion criteria Number of arms blinded; likely that trial. 1982. Journal of the Used validated acne scale 3 participants were American Academy of no Split face design blinded; no ITT Dermatology Acne scale No analysis Trial ID None Intervention: arm 1 3. Missing Gratton 1982 Inclusion details CLIND 1% solution + outcome data Country Participants with moderate to severe acne PLC capsule (efficacy) High;17% Canada (defined as presence of a minimum of 12 to 70 Intervention: arm 2 discontinued - Study type inflammatory papules and pustules, and a PLC capsule + PLC imbalanced RCT maximum of 6 nodulocystic lesions on the face solution between arms Source of funding above the jawline). Coded intervention: (more in placebo Not reported. arm 1 arm); no ITT Analysis method CLIND-topical + PLC-oral 4. Outcome Intention to treat or Coded intervention: measurement completers analysis Exclusion details arm 2 Participants with a history of gastrointestinal (efficacy) completers PLC-oral + PLC-topical disease..Participants who had received Some concerns;not Treatment category systemic or topical antibiotics, systemic or reported if Topical non-retinoids ± topical steroids, or androgenic drugs within 30 assessment of other treatment days of starting study medication. outcome was blinded 5. Selective .Females who had been on oral contraceptives reporting for 3 months, or made a change in oral Some concerns;not contraceptives within the previous 3 months; reported if trial pregnancy. protocol was Number included registered Number randomised: arm 1 6. Overall bias 121 High Number randomised: arm 2 124 Number completed: arm 1 105 Number completed: arm 2 97 Study details N=175 Interventions Results Cochrane RoB Reference Treatment duration Skin irritation (n/N): Tool v2.0

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Study details Participants Interventions Outcomes and results Comments Jones, E. L. C., A. F.Topical Characteristics (weeks) arm 1 1. Randomisation erythromycin vs blank vehicle Sex 12 5 Some concerns;no in a multiclinic acne study. mixed Treatment duration Skin irritation (n/N): information 1981. Archives of Dermatology age (other information) category arm 2 provided Trial ID ERYTH 13-20, n=31; 21-30, n=46; 31-40, n=3; 12 to <24 weeks 9 2. Deviation from Jones 1981 41+, n=1; not known=0. Number of arms Skin irritation (n/N): intervention Country 2 arm 1 Some United States Vehicle 13-20, n=29; 21-30, n=39; 31-40, n=6; Split face design 90 concerns;double- Study type 41+, n=0; not known=1. No Skin irritation (n/N): blinded but not clear who was RCT Inclusion/exclusion criteria Intervention: arm 1 arm 2 blinded; not clear if Source of funding Used validated acne scale BPO 5%/ERYTH 3% gel 85 ITT analysis was Not reported. no Intervention: arm 2 done Analysis method Acne scale Vehicle 3. Missing Intention to treat or Unclear, type of lesion x counts scale Coded intervention: outcome data completers analysis Inclusion details arm 1 (efficacy) completers Males and females aged 12 years or older, BPO-topical + ERYTH- Some seeking medical care for acne or recruited topical volunteers, but otherwise in good general concerns;more Coded intervention: than 5% health..Facial acne grades 2 or 3 on the arm 2 withdrawals - severity scale (grade 2: a moderate number of Vehicle balanced between comedones, papules, and small cysts, occasional pustules, and inflammation; grade Treatment category arms 3: a great number of lesions with deeper and Topical or combination 4. Outcome larger cysts and minimal scarring)..Minimum of measurement 10 papular inflammatory acne lesions in the (efficacy) facial area..Participants could be pregnant or Some concerns;not of childbearing age..Unresponsive to treatment clear if blinded with oral tetracycline hydrochloride, topical 5. Selective benzoyl peroxide, and tretinoin. reporting Exclusion details Some concerns;not Children aged <12 years of age..Participants reported if trial could not be planning to move within 12 protocol was weeks..Use of concomitant antibiotics given registered for systemic effect or another topical acne 6. Overall bias treatment, unless it was possible to High discontinue such treatment 3 weeks before the start of the study.

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Study details Participants Interventions Outcomes and results Comments Number included Number randomised: arm 1 90 Number randomised: arm 2 85 Number completed: arm 1 81 Number completed: arm 2 75 Study details N=223 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Jones, T. M., L.,Monroe, Sex (weeks) arm 1 1. Randomisation E.,Weiss, J.,Levy, S.A mixed 8 14 Some concerns;no multicentre, double-blind, age (mean±SD) Treatment duration Skin irritation (n/N): information parallel-group study to 18.5±5.8 category arm 2 provided evaluate 3% erythromycin/5% Inclusion/exclusion criteria 6 to <12 weeks 6 2. Deviation from benzoyl peroxide dual-pouch Used validated acne scale Number of arms Skin irritation (n/N): intervention pack for acne vulgaris. 2002. no 2 arm 1 Low;double- Clinical Drug Investigation blinded & ITT Acne scale Split face design 112 Trial ID analysis Physician's Global Assessment No Skin irritation (n/N): Jones 2002 (PGA)/Physician’s Global Acne Severity Score Intervention: arm 1 arm 2 3. Missing Country outcome data Inclusion details BPO 5%/ERYTH 3% gel 111 United States (efficacy) Male and females aged =13 years..Moderate (dual pouch pack) Participant reported Some Study type to moderately severe acne vulgaris (overall Intervention: arm 2 improvement (n/N): arm concerns;Unclear RCT acne severity score =1.5 on the Physician’s Vehicle 1 how many Source of funding Global Acne Severity Scale, 15 to 80 2/112 Coded intervention: discontinued Dermick Laboratories, US. inflammatory lesions, 20 to 140 comedones, Participant reported arm 1 during the trial Analysis method and =2 nodules or cysts measuring greater BPO-topical + ERYTH- improvement (n/N): arm 4. Outcome Intention to treat or than 5mm. The comedo count did not include topical 2 measurement completers analysis the nasal and nasolabial fold area). Treatment Coded intervention: 1.6/111 ITT with systemic antibiotics known to affect acne (efficacy) arm 2 Low;Assessors Method of ITT imputation and systemic corticosteroids should be Vehicle discontinued 4 weeks prior to study blinded not reported Treatment category commencement, and 6 months for oral 5. Selective Topical or combination retinoids. A 2-week washout period was reporting required for topical antibiotics and/or anti-acne Some concerns;not reported if trial

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Study details Participants Interventions Outcomes and results Comments medication, topical corticosteroids, and topical protocol was retinoids. registered Exclusion details 6. Overall bias Pregnant or lactating women..Participants with Some concerns beards or long sideburns..Participants with cystic acne or any other diseases affecting their condition or interfering with treatment evaluation. Number included Number randomised: arm 1 112 Number randomised: arm 2 111 Number completed: arm 1 112 Number completed: arm 2 110 Study details N=60 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Mucosal or cutaneous Tool v2.0 Kapadia, N. F. K., G.,Burhany, Sex (weeks) changes (n/N): arm 1 1. Randomisation T.,Nakhoda, T.Comparative mixed 24 30/30 Some concerns;no efficacy and safety and efficacy age (other information) Treatment duration Mucosal or cutaneous information of systemic 13-cis retinoic acid no age or sex data reported category changes (n/N): arm 2 provided 20mg/day vs. 40mg/day in Inclusion/exclusion criteria 24+ weeks 30/30 2. Deviation from acne vulgaris. 2005. Journal of Number of arms Change in mood (n/N): intervention Pakistan Association of Used validated acne scale no 2 arm 1 Some concerns;no Dermatologists information Acne scale Split face design 0/30 Trial ID provided Global Acne Grading System (GAGS) No Change in mood (n/N): Kapadia 2005 3. Missing Inclusion details Intervention: arm 1 arm 2 Country outcome data Participants with moderate to severe acne ISO<120.Daily<0.5 3/30 Pakistan (efficacy) vulgaris (graded using the Global Acne (20mg) Low Study type Grading System (GAGS)) attending an Intervention: arm 2 RCT outpatient clinical in Karachi. ISO<120.Daily=0.5 4. Outcome Source of funding (40mg) measurement (efficacy) Not reported. Coded intervention: Some concerns;no arm 1 ISO<120.Daily<0.5-oral

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Study details Participants Interventions Outcomes and results Comments Exclusion details Coded intervention: information Not reported. arm 2 provided Number included ISO<120.Daily=0.5-oral 5. Selective Number randomised: arm 1 Treatment category reporting 30 Oral isotretinoin Some concerns;not Number randomised: arm 2 reported if trial 30 protocol was registered Number completed: arm 1 30 6. Overall bias Some concerns Number completed: arm 2 30 Study details N=44 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Thrush/candidiasis Tool v2.0 Khanna, N.Treatment of acne Sex (weeks) (n/N): arm 1 1. Randomisation vulgaris with oral tetracylines. mixed 12 1/21 Some concerns;No 1993. Indian journal of age group Treatment duration Thrush/candidiasis detials on methods dermatology, venerology and =25 years category (n/N): arm 2 2. Deviation from leprology age (min/max) 12 to <24 weeks 1/23 intervention Trial ID 14/24 Number of arms High;No blinding; Khanna 1993 no ITT Inclusion/exclusion criteria 2 Country Used validated acne scale Split face design 3. Missing India no No outcome data (efficacy) Study type Acne scale Intervention: arm 1 High;Withdrawals RCT Unclear, type of lesion x counts scale TETRA 500 mg po bid of 23% - some due Source of funding Intervention: arm 2 Inclusion details to lack of efficacy & None (no conflicts of interest). MINO 50 mg po bid Males and females with moderately severe imbalanced Analysis method acne (defined when acne lesion score (ALS) Coded intervention: between groups Intention to treat or was 30 to 70) and severe acne (defined as arm 1 4. Outcome completers analysis ALS score of more than 70)..Participants who TETRA-oral measurement completers had taken oral antibiotics were included in the Coded intervention: (efficacy) Method of ITT imputation study after 1 month discontinuation of the arm 2 High;not blinded not reported antibiotics. MINO-oral 5. Selective Exclusion details Treatment category reporting Participants with acne conglobata..Pregnant Oral antibiotics Some concerns;not women or women using oral reported if trial

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Study details Participants Interventions Outcomes and results Comments contraceptives..Participants with obvious protocol was endocrinopathy. registered Number included 6. Overall bias Number randomised: arm 1 High 21 Number randomised: arm 2 23 Number completed: arm 1 15 Number completed: arm 2 19 Study details N=32 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin redness (n/N): arm Tool v2.0 Kim, T. I. A., H. J.,Kang, I. Sex (weeks) 1 1. Randomisation H.,Jeong, K. H.,Kim, N. I.,Shin, mixed 16 2/14 Some concerns;no M. K.Nonablative fractional age (mean±SD) Treatment duration Skin redness (n/N): arm information about laser-assisted daylight 24.75±3.5999999999999996 category 2 allocation photodynamic therapy with concealment age (min/max) 12 to <24 weeks 0/14 topical methyl aminolevulinate provided 19/45 Treatment intensity Pigment changes (n/N): for moderate to severe facial 2. Deviation from Inclusion/exclusion criteria Total 2 sessions, once arm 1 acne vulgaris: Results of a every 2 weeks. FU visits 1/14 intervention randomized and comparative Used validated acne scale at 2, 6, 10 and 14 wks Pigment changes (n/N): Some study. 2017. Photodermatology no after last session. arm 2 concerns;Not Photoimmunology and Acne scale Number of arms 1/14 reported if Photomedicine Investigator's Global Assessment scale (IGA) participants were 2 Participant reported Trial ID Inclusion details blinded; not Split face design improvement (n/N): arm Kim 2017 Participants aged between 19 and 45 reported if ITT No 1 Country years..Active acne lesions and Fitzpatrick skin analysis was done Intervention: arm 1 12/14 Korea, Republic of phototypes III to IV; acne severity grade 3 or 4 3. Missing according to the IGA. MAL 16%-DL PDT Participant reported Study type outcome data Intervention: arm 2 improvement (n/N): arm RCT Exclusion details (efficacy) History of photosensitive disorders..Use of NAFL + MAL 16%-DL 2 Source of funding High;more than 5% medications such as oral isotretinoin for 3 PDT 14/14 Galderma Research & withdrawals - months and oral contraceptives or antibiotics Coded intervention: Development (no conflicts of balanced between for 4 weeks, topical treatments or facial arm 1 interest). arms procedures for 4 weeks..Pregnant or lactating MAL-DL-PDT 4. Outcome Analysis method women..Participants were prohibited from Intention to treat or measurement

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Study details Participants Interventions Outcomes and results Comments completers analysis using oral or topical medications for treatment Coded intervention: (efficacy) completers of acne during the study. arm 2 Low Number included NAFL + MAL-DL-PDT 5. Selective Number randomised: arm 1 Treatment category reporting 16 Energy based (light / Some concerns;not Number randomised: arm 2 laser) reported if trial 16 protocol was Number completed: arm 1 registered 14 6. Overall bias Number completed: arm 2 High 14 Study details N=35 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Kuhlman, D. S. C., J. P.A Sex (weeks) arm 1 1. Randomisation comparison of clindamycin mixed 12 2 Some concerns;no phosphate 1 percent topical age (min/max) Treatment duration Skin irritation (n/N): information lotion and placebo in the 12/30 category arm 2 provided treatment of acne vulgaris. Inclusion/exclusion criteria 12 to <24 weeks 0 2. Deviation from 1986. Cutis Used validated acne scale Number of arms Skin irritation (n/N): intervention Trial ID no 2 arm 1 Some Kuhlman 1986 concerns;double- Acne scale Split face design 21 blinded but not Country None No Skin irritation (n/N): clear who was United States Intervention: arm 1 arm 2 Inclusion details blinded Study type Men and women aged 12 to 30 CLIND 1% lotion 14 3. Missing RCT years..Moderate to severe acne vulgaris Intervention: arm 2 outcome data Source of funding defined as 12 to 70 inflammatory papules and Vehicle (efficacy) Not reported. no more than 6 cystic lesions on the face Coded intervention: High;not reported Analysis method above the jawline. arm 1 how many Intention to treat or Exclusion details CLIND-topical participants were completers analysis Participants sensitive to clindamycin..Pregnant Coded intervention: randomised to completers or nursing women..Participants with chronic arm 2 each arm; not bowel disease or frequent periodic Vehicle reported how many diarrhoea..Participants requiring additional Treatment category withdrew acne treatment, those who had received Topical or combination 4. Outcome systemic antibiotics, steroids, or androgens measurement within the past 30 days or topical acne (efficacy) medications within the past 14 days, and

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Study details Participants Interventions Outcomes and results Comments participants who had started or stopped using Some concerns;not oral contraceptives in the past 60 days. reported if Number included assessment of Number randomised: arm 1 outcome was na blinded Number randomised: arm 2 5. Selective na reporting Number completed: arm 1 Some concerns;not 21 reported if trial protocol was Number completed: arm 2 registered 14 6. Overall bias High Study details N=30 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Lassus, A. J., T.,Lauharanta, Sex (weeks) arm 1 1. Randomisation J.Motretinide versus benzoyl mixed 8 1 Some concerns;no peroxide in the treatment of age (other information) Treatment duration Skin irritation (n/N): information acne vulgaris. 1984. no age data reported category arm 2 provided Dermatologica Inclusion/exclusion criteria 6 to <12 weeks 11 2. Deviation from Trial ID Used validated acne scale Number of arms Skin irritation (n/N): intervention Lassus 1984 no 2 arm 1 High;open label; not reported if ITT Country Acne scale Split face design 15 analysis was done Finland None No Skin irritation (n/N): 3. Missing Study type Inclusion details Intervention: arm 1 arm 2 outcome data RCT Participants diagnosed with acne vulgaris of motretinide 1% cream 15 (efficacy) Source of funding the papulopustular type. Intervention: arm 2 High;13% Not reported. BPO 5% gel Exclusion details withdrawals - Analysis method Not reported. Coded intervention: balanced between Intention to treat or Number included arm 1 arms; no ITT completers analysis Number randomised: arm 1 MOT-topical completers 4. Outcome 15 Coded intervention: measurement Number randomised: arm 2 arm 2 (efficacy) 15 BPO-topical High;open-labeled Number completed: arm 1 Treatment category 5. Selective 13 Topical or combination reporting

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Study details Participants Interventions Outcomes and results Comments Number completed: arm 2 Some concerns;not 13 reported if trial protocol was registered 6. Overall bias High Study details N=285 Interventions Results Cochrane RoB Reference Characteristics Treatment duration GI side effects (n/N): Tool v2.0 Leyden, J. J. S., V.,Berk, D. Sex (weeks) arm 1 1. Randomisation R.,Kaoukhov, A.Efficacy and mixed 12 6/76 Some concerns;no Safety of Sarecycline, a Novel, age (mean±SD) Treatment duration GI side effects (n/N): information Once-Daily, Narrow Spectrum 20.1676056338028±6.7286646771969361 category arm 2 provided Antibiotic for the Treatment of age (other information) 12 to <24 weeks 1/70 2. Deviation from Moderate to Severe Facial age data reported for 284 participants as 1 Number of arms GI side effects (n/N): intervention Acne Vulgaris: Results of a person in PL group withdrew consent and did 4 arm 3 Low;double- Phase 2, Dose-Ranging Study. not have post-baseline efficacy assessment Split face design 2/66 blinded; likely 2018. Journal of Drugs in participant-blinded; Inclusion/exclusion criteria No GI side effects (n/N): Dermatology: JDD a modified ITT was Used validated acne scale Intervention: arm 1 arm 4 Trial ID done no SAR 0.75 mg/kg 4/73 Leyden 2018 3. Missing Acne scale Intervention: arm 2 Country outcome data Investigator's Global Assessment scale (IGA) SAR 1.5 mg/kg United States (efficacy) Inclusion details Intervention: arm 3 Study type Some Males and females aged 12 to 45 SAR 3.0 mg/kg RCT concerns;14% years..Moderate to severe facial acne vulgaris Intervention: arm 4 Source of funding discontinued - characterised by 20 to 50 inflammatory PL Allergan plc, Ireland (conflicts balanced between lesions, 30 to 100 non-inflammatory lesions, Coded intervention: arms; ITT used of interest reported). and no more than 2 facial nodules. IGA arm 1 4. Outcome Analysis method baseline score of 3 ('moderate') or 4 SARE-oral measurement Intention to treat or ('severe')..Body weight between 52 kg and 88 Coded intervention: (efficacy) completers analysis kg at screening..Participants receiving arm 2 Some concerns;not ITT prohibited medications entered an appropriate SARE-oral reported if Method of ITT imputation washout period prior to screening assessment of LOCF? procedures..Females of childbearing potential Coded intervention: outcome was had to have a negative urine pregnancy test arm 3 blinded and use of an effective method of SARE-oral contraception. 5. Selective reporting High;Some of the

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Study details Participants Interventions Outcomes and results Comments Exclusion details Coded intervention: specified outcomes Use of other acne treatments, excessive sun arm 4 in the protocol not exposure, and tanning booths..Participants PLC-oral reported with dermatologic conditions of the face or Treatment category 6. Overall bias facial hair that could interfere with clinical Oral antibiotics High assessments of acne, facial sunburn..Prolonged Fridericia's corrected QT interval (>450 msec) on electrocardiogram..Allergy to tetracycline-class antibiotics or any component in the study drug..Pseudomembranous colitis or an antibiotic-associated colitis, cancer within the previous 6 months, or hepatitis, liver damage, or renal impairment. Number included Number randomised: arm 1 76 Number randomised: arm 2 70 Number randomised: arm 3 66 Number randomised: arm 4 73 Number completed: arm 1 64 Number completed: arm 2 60 Number completed: arm 3 57 Number completed: arm 4 64 Study details N=41 Interventions Results Cochrane RoB Reference Characteristics Treatment intensity Skin redness (n/N): arm Tool v2.0 Mei, X. S., W.,Piao, Sex Total 4 sessions, once 1 1. Randomisation Y.Effectiveness of mixed every week. 3/21 High;Allocation not photodynamic therapy with age (mean±SD) Assessments 1-wk after concealed topical 5-aminolevulinic acid 24 each session so have

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Study details Participants Interventions Outcomes and results Comments and intense pulsed light in Inclusion/exclusion criteria assumed endpoint is at Skin redness (n/N): arm 2. Deviation from Chinese acne vulgaris patients. Used validated acne scale 4th treatment (see 2 intervention 2013. Photodermatology no table1) 0/20 Low;Participants & Photoimmunology and Acne scale Number of arms Skin irritation (n/N): investigators Photomedicine Global Acne Severity Scale (GEA Scale) 2 arm 1 blinded Trial ID Inclusion details Split face design 21/21 3. Missing Mei 2013 Chinese patients aged over 18 No Skin irritation (n/N): outcome data Country years..Participants with II–IV facial acne Intervention: arm 1 arm 2 (efficacy) Low;No withrawals China according to Pillsbury grade and Fitzpatrick 5ALA 10%-IPL-PDT 20/20 / loss to follow-up. Study type skin type II–IV. Intervention: arm 2 RCT Exclusion details IPL-PT + Vehicle 4. Outcome Source of funding Participants exposed to systemic retinoid Coded intervention: measurement Not reported (no conflicts of treatment in the last 6 months, systemic arm 1 (efficacy) Low;Assessor interest). antibiotics treatment or contraceptive and 5ALA-IPL-PDT photosensitive drugs in the previous month, blinded Analysis method Coded intervention: local acne drug treatment in the last 2 5. Selective Intention to treat or arm 2 weeks..Participants with a tendency to form reporting completers analysis IPL + Vehicle ITT keloids or with a history of Some concerns;not photosensitivity..Pregnant or breastfeeding Treatment category reported if trial Method of ITT imputation women. Energy based (light / protocol was not reported laser) Number included registered Number randomised: arm 1 6. Overall bias 21 High Number randomised: arm 2 20 Number completed: arm 1 21 Number completed: arm 2 20 Study details N=90 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Breast tenderness Tool v2.0 Miller, J. A. W., F. T.,Dowd, P. Sex (weeks) (n/N): arm 1 1. Randomisation M.Anti-androgen treatment in female 26 5/26 Some concerns;no women with acne: A controlled age (min/max) Treatment duration Breast tenderness information trial. 1986b. British Journal of 16/36 category (n/N): arm 2 provided Dermatology age (other information) 24+ weeks 3/24 2. Deviation from CPA/EE mean age=24.2 (range 18-34); intervention

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Study details Participants Interventions Outcomes and results Comments Trial ID NOR/EE mean age 24.2 (range 18-36); CPA Number of arms Breast tenderness Some Miller 1986b mean age=22.8 (range 16-30) 3 (n/N): arm 3 concerns;double- Country Inclusion/exclusion criteria Split face design 4/26 blinded but not United Kingdom Used validated acne scale No Sexual dysfunction clear who was blinded; not Study type no Intervention: arm 1 (n/N): arm 1 reported if ITT RCT Acne scale CPA 2mg/EE 0.05 mg 0/26 analysis was done Source of funding Leeds Grading Scale, Cunliffe (days 5-25) + PL (days 5- Sexual dysfunction 3. Missing Schering Chemicals Ltd. Inclusion details 14) (n/N): arm 2 outcome data Women aged between 16 and 36 Intervention: arm 2 1/24 Analysis method (efficacy) years..Moderate to severe acne (graded NOR 1mg/EE 0.05mg Sexual dysfunction Intention to treat or High;Withdrawal according to Burke & Cunliffe, 1984)..Any (days 5-25) + PL (days 5- (n/N): arm 3 completers analysis imbalanced acne medication (other than contraceptive pill) 14) 1/26 completers stopped 6 weeks prior to study participation. between groups Intervention: arm 3 Change in mood (n/N): (more in Diane and Oral contraception was continued until the CPA 50mg (days 5-14), arm 1 commencement of the trial. placebo arm) and then EE 0.05 mg (days 5- 3/26 more than 5% Exclusion details 25) Change in mood (n/N): Participants with medical contraindications to 4. Outcome Coded intervention: arm 2 measurement the study treatment..Current smokers (more arm 1 3/24 than 5 cigarettes daily). (efficacy) CPA-oral + EE-oral + Change in mood (n/N): Some concerns;not Number included PLC-oral arm 3 reported if Number randomised: arm 1 Coded intervention: 3/26 assessment of 28 arm 2 Breakthrough bleeding outcome was Number randomised: arm 2 NOR-oral + EE-oral + (n/N): arm 1 blinded 32 PLC-oral 2/26 5. Selective Number randomised: arm 3 Coded intervention: Breakthrough bleeding reporting 30 arm 3 (n/N): arm 2 Some concerns;not Number completed: arm 1 CPA-oral + EE-oral 3/24 reported if trial 24 Treatment category Breakthrough bleeding protocol was Number completed: arm 2 Hormonal contraceptives (n/N): arm 3 registered 26 / Hormone-modifying 4/26 6. Overall bias agents Number completed: arm 3 High 26 Study details N=968 Interventions Results Cochrane RoB Reference Characteristics Treatment duration GI side effects (n/N): Tool v2.0 Moore, A. G., L. J.,Bruce, Sex (weeks) arm 1 1. Randomisation S.,Sadick, N.,Tschen, mixed 12 22/481 Some concerns;no E.,Werschler, P.,Cook-Bolden,

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Study details Participants Interventions Outcomes and results Comments F. E.,Dhawan, S. S.,Forsha, age (other information) Treatment duration GI side effects (n/N): information D.,Gold, M. H.,et al.,Once- SAR mean age=19.6 (range 10-45); PL mean category arm 2 provided Daily Oral Sarecycline 1.5 age=19.8 (range 10-45) 12 to <24 weeks 12/483 2. Deviation from mg/kg/day Is Effective for Inclusion/exclusion criteria Number of arms Thrush/candidiasis intervention Moderate to Severe Acne Used validated acne scale 2 (n/N): arm 1 Low;double- Vulgaris: results from Two no Split face design 3/481 blinded - Identically Designed, Phase 3, Acne scale No Thrush/candidiasis participants were Randomized, Double-Blind Investigator's Global Assessment scale (IGA) (n/N): arm 2 likely blinded; ITT Clinical Trials. 2018. Journal of Intervention: arm 1 SAR 1.5 mg/kg 0/483 analysis was done drugs in dermatology Inclusion details Participants aged 9 to 45 years, weighing 33 Intervention: arm 2 3. Missing Trial ID to 136 kg..Score of 3 (moderate) or 4 (severe) outcome data Moore 2018;Trial 1 PL on the IGA scale for inflammatory lesions of (efficacy) Country Coded intervention: Some acne; 20 to 50 inflammatory and =100 non- arm 1 United States inflammatory lesions, and =2 nodules. concerns;Discontin SARE-oral uations 15% - Study type Exclusion details RCT Coded intervention: balanced between Dermatologic condition or facial hair, any arm 2 Source of funding arms; few due chronic illness interfering with study PLC-oral Allergan plc, Ireland (conflicts assessment, allergy or resistance to inefficacy Treatment category of interest reported). tetracyclines, drug-induced acne, hormonal 4. Outcome Oral antibiotics Analysis method contraceptive initiation, systemic retinoids, measurement Intention to treat or systemic corticosteroids, androgens, or anti- (efficacy) completers analysis androgens within 12 weeks prior to study. Some concerns;not reported if ITT Number included assessment of Method of ITT imputation Number randomised: arm 1 outcome was MI (no other details reported) 483 blinded Number randomised: arm 2 5. Selective 485 reporting Number completed: arm 1 Some 420 concerns;Some of Number completed: arm 2 the specified 405 outcomes in the protocol not reported; report used IGA success for facial acne defined as a =2- point decrease

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Study details Participants Interventions Outcomes and results Comments from baseline and a score of 0 (clear) or 1 (almost clear) - differs from the protocol 6. Overall bias Some concerns Study details N=1034 Interventions Results Cochrane RoB Reference Characteristics Treatment duration GI side effects (n/N): Tool v2.0 Moore, A. G., L. J.,Bruce, Sex (weeks) arm 1 1. Randomisation S.,Sadick, N.,Tschen, mixed 12 10/513 Some concerns;no E.,Werschler, P.,Cook-Bolden, age (other information) Treatment duration GI side effects (n/N): information F. E.,Dhawan, S. S.,Forsha, SAR mean age=20.4 (range 9-44); PL mean category arm 2 provided D.,Gold, M. H.,et al.,Once- age=19.7 (range 10-44) 12 to <24 weeks 5/513 2. Deviation from Daily Oral Sarecycline 1.5 Inclusion/exclusion criteria Number of arms Thrush/candidiasis intervention mg/kg/day Is Effective for Used validated acne scale 2 (n/N): arm 1 Low;double- Moderate to Severe Acne no Split face design 1/513 blinded - Vulgaris: results from Two participants were Acne scale No Thrush/candidiasis Identically Designed, Phase 3, likely blinded; ITT Investigator's Global Assessment scale (IGA) Intervention: arm 1 (n/N): arm 2 Randomized, Double-Blind analysis was done Inclusion details SAR 1.5 mg/kg 0/513 Clinical Trials. 2018. Journal of 3. Missing Participants aged 9 to 45 years, weighing 33 Intervention: arm 2 drugs in dermatology outcome data to 136 kg..Score of 3 (moderate) or 4 (severe) PL Trial ID (efficacy) on the IGA scale for inflammatory lesions of Moore 2018;Trial 2 Coded intervention: Some acne; 20 to 50 inflammatory and =100 non- Country arm 1 concerns;Discontin inflammatory lesions, and =2 nodules. United States SARE-oral uations 15% - Exclusion details Study type Coded intervention: balanced between Dermatologic condition or facial hair, any RCT arm 2 arms; few due chronic illness interfering with study PLC-oral inefficacy Source of funding assessment, allergy or resistance to Treatment category 4. Outcome Allergan plc, Ireland (conflicts tetracyclines, drug-induced acne, hormonal Oral antibiotics measurement of interest reported). contraceptive initiation, systemic retinoids, (efficacy) Analysis method systemic corticosteroids, androgens, or anti- Some concerns;not Intention to treat or androgens within 12 weeks prior to study. reported if completers analysis Number included ITT assessment of Number randomised: arm 1 outcome was Method of ITT imputation 519 blinded MI (no other details reported)

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Study details Participants Interventions Outcomes and results Comments Number randomised: arm 2 5. Selective 515 reporting Number completed: arm 1 Some 433 concerns;Some of Number completed: arm 2 the specified 444 outcomes in the protocol not reported; report used IGA success for facial acne defined as a =2- point decrease from baseline and a score of 0 (clear) or 1 (almost clear) - differs from the protocol 6. Overall bias Some concerns Study details N=214 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Pariser, D. M. T., D. M.,Clark, Sex (weeks) arm 1 1. Randomisation S. D.,Jones, T. M.,Liu, mixed 12 16/70 Some Y.,Graeber, M.The efficacy and age (mean±SD) Treatment duration Skin irritation (n/N): concerns;reported safety of adapalene gel 0.3% 17.3±5.07 category arm 2 only that in the treatment of acne medication was age (median) 12 to <24 weeks 13/70 vulgaris: A randomized, dispensed by a 16 Number of arms Skin irritation (n/N): multicenter, investigator- 3 arm 3 third party to blinded, controlled comparison age (min/max) protect blinding Split face design 0/74 study versus adapalene gel 12/45 No 2. Deviation from 0.1% and vehicle. 2005. Cutis Inclusion/exclusion criteria intervention Intervention: arm 1 Trial ID Used validated acne scale Some concerns;not ADAP 0.3% gel Pariser 2005 yes reported if Intervention: arm 2 Country Acne scale participants were ADAP 0.1% gel United States Leeds Revised Grading Scale blinded; ITT Intervention: arm 3 Study type Inclusion details analysis was done Vehicle RCT Participants aged 12 to 40 years..Moderate to 3. Missing moderately severe acne vulgaris; minimum of outcome data

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Study details Participants Interventions Outcomes and results Comments Source of funding 20 inflammatory facial lesions (not >2 Coded intervention: (efficacy) Galderma Research & nodules/cysts), 20 non-inflammatory facial arm 1 Some Development (conflicts of lesions; global facial severity grade 4 to 10 ADAP-topical concerns;Withdraw interest reported). according to the Leeds Revised Acne Grading Coded intervention: al imbalanced Analysis method System..Washout periods for certain topical arm 2 between groups Intention to treat or and systemic treatments were ADAP-topical (21% in the required..Negative urine pregnancy test results adapalene gel completers analysis Coded intervention: required at screening and at the final visit for 0.3% arm, only 7% ITT arm 3 women of childbearing potential. in the adapalene Method of ITT imputation Vehicle Exclusion details 0.1% gel arm ) baseline assigned? Treatment category Not reported. 4. Outcome Topical retinoids Number included measurement Number randomised: arm 1 (efficacy) 70 Low;investigator- Number randomised: arm 2 blinded 70 5. Selective Number randomised: arm 3 reporting 74 Some concerns;not reported if trial Number completed: arm 1 protocol was 55 registered Number completed: arm 2 6. Overall bias 65 High Number completed: arm 3 62 Study details N=498 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Participant reported Tool v2.0 Pariser, D. M. R., P.,Cook- Sex (weeks) improvement (n/N): arm 1. Randomisation Bolden, F. E.,Korotzer, A.An mixed 12 1 Some aqueous gel fixed combination age (mean±SD) Treatment duration 169/253 concerns;insufficie of clindamycin phosphate 1.2% 18.7±5.82 category Participant reported nt information and benzoyl peroxide 3.75% provided on age (median) 12 to <24 weeks improvement (n/N): arm for the once-daily treatment of allocation 17 Number of arms 2 moderate to severe acne concealment 2 101/245 vulgaris. 2014. Journal of age (min/max) Split face design 2. Deviation from Drugs in Dermatology 12/40 No intervention Trial ID age (other information) Low;double- Pariser 2014 Sig. diff (p=0.02) between age of groups

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Study details Participants Interventions Outcomes and results Comments Country Inclusion/exclusion criteria Intervention: arm 1 blinded & ITT United States Used validated acne scale BPO 3.75%/CLIND 1.2% analysis Study type no gel 3. Missing RCT Acne scale Intervention: arm 2 outcome data Source of funding Evaluator's Global Severity Scale (EGSS) Vehicle (efficacy) Valeant Pharmaceuticals North Inclusion details Coded intervention: Some America LLC. Males and females of any race and ethnicity, arm 1 concerns;Withdraw al imbalanced Analysis method aged 12 to 40 years..Moderate to severe acne BPO-topical + CLIND- between groups, Intention to treat or vulgaris (a score of 3 or 4 on the Global topical &>5% completers analysis Severity Score (EGSS), presenting with 20 to Coded intervention: ITT 40 inflammatory lesions (papules, pustules, arm 2 4. Outcome Method of ITT imputation and nodules), 20 to 100 non-inflammatory Vehicle measurement (efficacy) MI MCMC lesions (open and closed comedones), and =2 Treatment category nodules..Women of childbearing age were Low Topical or combination required to have a negative urine pregnancy 5. Selective test and to agree to use an effective form of reporting contraception during the study period..A Some concerns;not washout period of up to 1 month was required reported if trial for participants who used previous prescription protocol was and over-the-counter acne treatments registered (including, topical (face) and systemic 6. Overall bias treatments: topical astringents and abrasives Some concerns (1 week); topical anti-acne products, including soaps containing antimicrobials, and known comedogenic products (2 weeks); topical retinoids, retinol, and systemic acne treatments (4 weeks); and systemic retinoids (6 months). Exclusion details Not reported. Number included Number randomised: arm 1 253 Number randomised: arm 2 245 Number completed: arm 1 234

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Study details Participants Interventions Outcomes and results Comments Number completed: arm 2 213 Study details N=153 Interventions Results Cochrane RoB Reference Characteristics Treatment intensity Skin redness (n/N): arm Tool v2.0 Pariser, D. M. E., L. Sex Total 4 sessions, once 1 1. Randomisation F.,Bukhalo, M.,Waterman, mixed every 2 weeks. Endpoint 4/100 Low G.,Jarratt, M.,Bhatia, age (min/max) is 6-wks after last Skin redness (n/N): arm 2. Deviation from A.,Greenstein, D.,Hamzavi, 12/36 treatment. 2 intervention F.,Kantor, J.,Speelman, P. age (other information) Number of arms 0/53 Low;double- N.,Murakawa, G. J.,Tichy, MAL-PDT median age=17 (range 12-36), <18 2 Pigment changes (n/N): blinded; according E.,Zaengelin, A.,Frankel, years-old, n=59; Vehicle median age=17 Split face design arm 1 to the study E.,Werschler, W.Photodynamic (range 12-35), <18 years-old, n=31 No 2/100 protocol it is therapy with methyl quadruple-blinded Inclusion/exclusion criteria Intervention: arm 1 Pigment changes (n/N): aminolaevulinate 80 mg (participant, care Used validated acne scale MAL 8%-RED-PDT arm 2 g^-1 for severe provider, no Intervention: arm 2 0/53 facial acne vulgaris: A investigator, Vehicle-RED-PDT randomized vehicle-controlled Acne scale outcomes study. 2016. British Journal of Investigator's Global Assessment scale (IGA) Coded intervention: assessor); ITT Dermatology Inclusion details arm 1 analysis was done MAL-RED-PDT Trial ID Males and females aged 12 to 35 3. Missing Pariser 2016 years..Severe facial acne vulgaris (defined by Coded intervention: outcome data Country an IGA rating score of 4); 27 to 75 arm 2 (efficacy) United States inflammatory lesions (papules, pustules and Vehicle + RED Some no more than 3 nodules) and 20 to 100 non- Study type Treatment category concerns;16% inflammatory lesions (open and closed RCT Energy based (light / withdrawals - comedones) on the face; Fitzpatrick skin types laser) Source of funding imbalanced I to VI. Confirmed using standardised clinical between arms as Photocure ASA, Norway photographs. Females of childbearing (conflicts of interest reported). 12 out of 17 in the potential were required to use appropriate active arm Analysis method contraception (same product and dose if using discontinued due Intention to treat or an oral contraceptive) for at least 14 days to adverse events completers analysis before the first treatment and during the study. and none in the ITT Exclusion details other arm Method of ITT imputation Participants with acne conglobata, acne 4. Outcome LOCF fulminans, secondary acne, melanoma or measurement dysplastic naevi in the treatment area..Facial (efficacy) har that might interfere with study Low assessments..Participants with porphyria,

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Study details Participants Interventions Outcomes and results Comments cutaneous photosensitivity or known allergy to 5. Selective methyl aminolaevulinate, components of the reporting cream or similar photosensitisers..Participants Low with moderate-to-very-severe facial acne 6. Overall bias scarring..Pregnant or nursing Some concerns females..Systemic acne treatment (oral antibiotics within 1 month or oral isotretinoin within 6 months); topical treatments (other than medicated cleansers) within 14 days; facial procedures (for example, dermabrasion, chemical or laser peels); exposure to ultraviolet radiation (other than sunlight) within 1 month and concomitant hormonal therapy for acne were prohibited. Number included Number randomised: arm 1 100 Number randomised: arm 2 53 Number completed: arm 1 83 Number completed: arm 2 46 Study details N=60 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Parsad, D. P., R.,Nagpal, Sex (weeks) arm 1 1. Randomisation R.,Negi, K. S.Azithromycin mixed 12 3/22 Some concerns;no monthly pulse vs daily age (min/max) Treatment duration Skin irritation (n/N): information doxycycline in the treatment of 16 category arm 2 provided acne vulgaris. 2001. Journal of age (other information) 12 to <24 weeks 4/28 2. Deviation from Dermatology no other data on age reported Number of arms intervention Trial ID Some concerns;not Inclusion/exclusion criteria 2 Parsad 2001 reported if Used validated acne scale Split face design investigators/partici Country no No pants were India Intervention: arm 1 Acne scale blinded; ITT Study type DOXY 100mg + TRET Leeds Grading Scale, Cunliffe analysis was done RCT 0.05% cream

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Study details Participants Interventions Outcomes and results Comments Source of funding Inclusion details Intervention: arm 2 3. Missing Not reported. Participants with moderate to severe acne AZITH 500 mg + TRET outcome data Analysis method (grade 2 to 8) on the Burke & Cunliffe scale. 0.05% cream (efficacy) Intention to treat or Coded intervention: Some completers analysis arm 1 concerns;17% ITT DOXY-oral + TRET- withdrawals - Method of ITT imputation Exclusion details topical imbalanced Participants aged <16 years of between arms Unclear Coded intervention: age..Participants with sensitivity to any drugs arm 2 (more in the 100 used in the study..Women who were pregnant, AZITH-oral + TRET- mg doxycycline + planning pregnancy, or nursing a child. topical 0.05% topical Number included tretinoin cream Number randomised: arm 1 arm) 30 4. Outcome Number randomised: arm 2 measurement 30 (efficacy) Some concerns;not Number completed: arm 1 reported if 22 assessment of Number completed: arm 2 outcome was 28 blinded 5. Selective reporting Some concerns;not reported if trial protocol was registered 6. Overall bias High Study details N=161 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Richter, J. R. B., M. T.,De Sex (weeks) arm 1 1. Randomisation Boulle, Klvm,Degreef, H. mixed 12 5 Some concerns;no J.,Poli, F.Efficacy of a fixed age (mean±SD) Treatment duration Skin irritation (n/N): information clindamycin phosphate 1.2%, 19.7±2.9 category arm 2 provided tretinoin 0.025% gel age (min/max) 12 to <24 weeks 3 2. Deviation from formulation (Velac) in the 14/26 intervention topical control of facial acne Low;double-

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Study details Participants Interventions Outcomes and results Comments lesions. 1998a. Journal of Inclusion/exclusion criteria Number of arms Skin irritation (n/N): blinded - likely that dermatological treatment Used validated acne scale 2 arm 1 participants were Trial ID no Split face design 72 blinded; ITT Richter 1998a Acne scale No Skin irritation (n/N): analysis was done Country Cook Intervention: arm 1 arm 2 3. Missing Europe Inclusion details CLIND 1.2%/TRET 73 outcome data Study type Outpatients aged 14 to 26 years..Facial acne 0.025% gel (efficacy) Some RCT (severity grades of 3 and higher according to Intervention: arm 2 concerns;more Source of funding the modified scoring scale of Cook). TRET 0.025% gel than 5% Not reported. Exclusion details Coded intervention: withdrawals in one Use of tretinoin, topical or systemic antibiotics, Analysis method arm 1 arm, mainly due to irritants or hormonal treatments in the 4 weeks CLIND-topical + TRET- Intention to treat or adverse effects completers analysis prior to study commencement..Skin disorders topical 4. Outcome ITT likely to affect drug absorption or disorders Coded intervention: requiring medical treatment within 5 days prior measurement Method of ITT imputation arm 2 to study start..Known or suspected (efficacy) not reported TRET-topical hypersensitivity to the agents in CTG or Some concerns;not Treatment category related compounds..History of serious allergic reported if Topical or combination reactions to drug treatment..Pregnancy, assessment of lactation and/or use of oral contraceptives with outcome was a specific anti-androgenic action or any oral blinded contraceptive treatment started within 3 5. Selective months prior to study commencement. reporting Number included Some concerns;not Number randomised: arm 1 reported if trial 81 protocol was registered Number randomised: arm 2 80 6. Overall bias Some concerns Number completed: arm 1 69 Number completed: arm 2 69 Study details N=45 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Pigment changes (n/N): Tool v2.0 Sami, N. A. A., A. T.,Badawi, Sex (weeks) arm 1 1. Randomisation A. M.Phototherapy in the mixed 4 3/15 Some treatment of acne vulgaris.

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Study details Participants Interventions Outcomes and results Comments 2008. Journal of drugs in age (mean±SD) Treatment duration Pigment changes (n/N): concerns;methods dermatology 29 category arm 2 not reported Trial ID age (min/max) 0 to <6 weeks 0/15 2. Deviation from Sami 2008 20/38 Treatment intensity Pigment changes (n/N): intervention Country Inclusion/exclusion criteria Trial continued until 90% arm 3 Some Egypt Used validated acne scale lesion clearance 0/15 concerns;Not Study type no observed but 1-mo data Participant reported reported if participants were RCT Acne scale available. Total sessions improvement (n/N): arm at 1-mo are 4, 4 and 8, blinded Source of funding Burton 1 respectively, for PDL (1 Not reported. Inclusion details 15/15 3. Missing session, once a week), Males and females with moderate to severe Participant reported outcome data Analysis method IPL (1 session, once a facial acne according to Burton classification. improvement (n/N): arm (efficacy) Intention to treat or week) and BR-LED (2 Some concerns;not completers analysis 2 Exclusion details sessions every week) clear if/how many ITT 12/15 Participants with a history of topical acne groups participants treatment or systemic antibiotics within the Participant reported Number of arms discontinued past 2 weeks, or use of systemic steroids, improvement (n/N): arm 3 systemic retinoids, or anti-inflammatory drugs 3 4. Outcome measurement within the past 6 months..History of Split face design 6/15 (efficacy) photosensitivity..Pregnancy. No Low Number included Intervention: arm 1 5. Selective Number randomised: arm 1 595 nm PDL PT reporting 15 Intervention: arm 2 550 nm-1200 nm IPL PT Some concerns;not Number randomised: arm 2 reported if trial Intervention: arm 3 15 protocol was BR-LED PT Number randomised: arm 3 registered Coded intervention: 15 6. Overall bias Number completed: arm 1 arm 1 Some concerns 15 PDL Number completed: arm 2 Coded intervention: 15 arm 2 IPL Number completed: arm 3 15 Coded intervention: arm 3 BR-LED Treatment category Energy based (light / laser)

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Study details Participants Interventions Outcomes and results Comments Study details N=2010 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Schmidt, N. G., E. Sex (weeks) arm 1 1. Randomisation H.Clindamycin 1.2% tretinoin mixed 12 34 Some concerns;no 0.025% gel versus clindamycin age (mean±SD) Treatment duration Skin irritation (n/N): information about gel treatment in acne patients: 19.0501492537313±7.2507470119521908 category arm 2 allocation A focus on fitzpatrick skin concealment Inclusion/exclusion criteria 12 to <24 weeks 14 types. 2011. Journal of Clinical provided Used validated acne scale Number of arms Skin irritation (n/N): and Aesthetic Dermatology no 2 arm 1 2. Deviation from Trial ID intervention Acne scale Split face design 1008 Schmidt 2011 Some Evaluator's Global Severity Scale (EGSS) No Skin irritation (n/N): concerns;double- Country Intervention: arm 1 arm 2 Inclusion details blinded but not United States CLIND 1.2%/TRET 1002 Males and females aged over 12 years..Facial clear who was Study type acne vulgaris with 20 to 50 inflammatory 0.025% gel RCT blinded; ITT lesions (papules and pustules), 20 to 100 non- Intervention: arm 2 analysis was done Source of funding inflammatory lesions (open and closed CLIND 1.2% gel 3. Missing Not reported (conflicts of comedones), and not more than 2 nodules; Coded intervention: outcome data interest reported). Evaluators Global Severity Score (EGSS) of arm 1 (efficacy) Analysis method moderate or severe..Willing to undergo the CLIND-topical + TRET- Some Intention to treat or specified washout periods for topical topical concerns;16% antibiotics and other topical antibacterial drugs completers analysis Coded intervention: withdrawals - ITT (2 weeks); facial anti-inflammatory agents and arm 2 balanced between corticosteroids (4 weeks); retinoids, including Method of ITT imputation CLIND-topical arms (unclear how retinol (4 weeks)..Had undergone the specified LOCF Treatment category many due to washout periods of systemic treatments Topical or combination inefficacy); ITT including corticosteroids and intramuscular used injections (4 weeks); antibiotics (4 weeks); other systemic acne treatments (4 weeks); 4. Outcome systemic retinoids (6 months). measurement (efficacy) Exclusion details Some concerns;not Participated in a similar study within 30 days of reported if enrolment or participating in another assessment of study..Facial dermatological conditions that outcome was could hinder or obstruct clinical blinded evaluations..Use of other non-acne topical medication that could interfere with study 5. Selective treatment..Pregnant, nursing, planning a reporting pregnancy, or became pregnant during the Some concerns;not

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Study details Participants Interventions Outcomes and results Comments trial..Non-compliance with washout criteria for reported if trial topical or systemic treatment. protocol was Number included registered Number randomised: arm 1 6. Overall bias 1008 High Number randomised: arm 2 1002 Number completed: arm 1 859 Number completed: arm 2 838 Study details N=94 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Sklar, J. L. J., C.,Rizer, Sex (weeks) arm 1 1. Randomisation R.,Gans, E. H.Evaluation of mixed 13 13 Some concerns;no Triaz 10% Gel and age (min/max) Treatment duration Skin irritation (n/N): information Benzamycin in acne vulgaris. 16/30 category arm 2 provided 1996. Journal of Inclusion/exclusion criteria 12 to <24 weeks 4 2. Deviation from dermatological treatment Used validated acne scale Number of arms Skin irritation (n/N): intervention Trial ID no 3 arm 3 Some Sklar 1996 concerns;participa Acne scale Split face design 1 nts not blinded; ITT Country None No Skin irritation (n/N): United States not used Inclusion details Intervention: arm 1 arm 1 3. Missing Study type Males and females aged 16 to 30 BPO-topical 5%/ ERYTH- 32 outcome data RCT years..Moderate to moderately severe, topical 3% Skin irritation (n/N): (efficacy) Source of funding papular-pustular, facial acne vulgaris with a Intervention: arm 2 arm 2 Some Not reported. minimum number of inflamed BPO-topical 10% 30 concerns;5% Analysis method lesions..Willingness to co-operate and adhere Skin irritation (n/N): Intervention: arm 3 discontinued Intention to treat or to study criteria..Absence of interfering Vehicle arm 3 4. Outcome completers analysis medical and dermatological conditions and Coded intervention: 31 completers medications..Absence of pregnancy and measurement arm 1 (efficacy) avoidance of interference from oral BPO-topical + ERYTH- contraceptives. Low;Investigator topical blinded Exclusion details Coded intervention: Not reported. 5. Selective arm 2 reporting BPO-topical Some concerns;not

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Study details Participants Interventions Outcomes and results Comments Number included Coded intervention: reported if trial Number randomised: arm 1 arm 3 protocol was 30 Vehicle registered Number randomised: arm 2 Treatment category 6. Overall bias 32 Topical or combination Some concerns Number randomised: arm 3 32 Number completed: arm 1 28 Number completed: arm 2 30 Number completed: arm 3 28 Study details N=201 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Stein Gold, L. ,. C., L. E., Sex (weeks) arm 1 1. Randomisation Johnson, L. A., Gottschalk, R. mixed 12 6 Some concerns;no W.Is switching retinoids a age (mean±SD) Treatment duration Skin irritation (n/N): information sound strategy for the 19 category arm 2 provided treatment of acne vulgaris?. age (other information) 12 to <24 weeks 8 2. Deviation from 2008. Journal of drugs in ADAP mean age=18.5; ADAP then TAZ, mean Number of arms Skin irritation (n/N): intervention dermatology age=19.4. 2 arm 1 Some concerns;not Trial ID reported if Inclusion/exclusion criteria Split face design 98 Stein Gold 2008 participants were Used validated acne scale No Skin irritation (n/N): blinded; ITT Country no Intervention: arm 1 arm 2 United States analysis was done Acne scale ADAP 0.1% gel 100 3. Missing Study type None Intervention: arm 2 outcome data RCT ADAP 0.1% gel for 6 Inclusion details (efficacy) Source of funding weeks then TAZ 0.1% Males and females aged between 12 and 35 High;more than 5% Not reported (conflicts of years. cream for 6 weeks interest reported). withdrawals; not Coded intervention: clear how balanced Analysis method arm 1 between arms; no Intention to treat or .15 to 100 non-inflammatory lesions, at least ADAP-topical reasons reported completers analysis 20 inflammatory lesions, and no more than 3 Coded intervention: 4. Outcome ITT nodules. arm 2 measurement

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Study details Participants Interventions Outcomes and results Comments Method of ITT imputation Exclusion details ADAP-topical / TAZ- (efficacy) LOCF Participants with severe nodulocystic topical Low acne..Pregnant, nursing, or planning a Treatment category 5. Selective pregnancy during the study..Participants with Topical retinoids reporting facial hair that would interfere with study Some concerns;not assessments..Washout periods <4 weeks for reported if trial topical acne treatments or <6 months for protocol was systemic treatment..Participants with other registered dermatologic conditions requiring interfering 6. Overall bias treatment. High Number included Number randomised: arm 1 101 Number randomised: arm 2 100 Study details N=434 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Stein Gold, L., Weiss, J., Sex (weeks) arm 1 1. Randomisation Rueda, M.J., Liu, H. and mixed 12 45/213 Low Tanghetti, E., 2016. Moderate age (mean±SD) Treatment duration Skin irritation (n/N): 2. Deviation from and severe inflammatory acne 19.58±7.00 category arm 2 intervention vulgaris effectively treated with age (min/max) 12 to <24 weeks 34/212 Low;double- single-agent therapy by a new 12/57 Number of arms Skin irritation (n/N): blinded; ITT fixed-dose combination 3 arm 3 analysis was done adapalene 0.3%/benzoyl age (other information) ADAP 0.3%, range 12-57; Split face design 5/68 3. Missing peroxide 2.5% gel: a outcome data ADAP 0.1%, range 12-49; No Participant reported randomized, double-blind, (efficacy) parallel-group, controlled Vehicle, range=12-36 Intervention: arm 1 improvement (n/N): arm ADAP 0.3%/BPO 2.5% 1 Some study. American Journal of Inclusion/exclusion criteria gel 182/204 concerns;10% Clinical Dermatology, 2016, Used validated acne scale withdrawals - Intervention: arm 2 Participant reported 17(3), 293-303 no balanced between ADAP 0.1%/BPO 2.5% improvement (n/N): arm Trial ID Acne scale arms; ITT used gel 2 Stein Gold 2016 Investigator's Global Assessment scale (IGA) 4. Outcome Intervention: arm 3 na/na Country Inclusion details measurement Vehicle Participant reported United States Males and females. Moderate to severe (efficacy) improvement (n/N): arm Study type inflammatory facial acne, that is a score of 3 Coded intervention: Some concerns;not 3 RCT (moderate) or 4 (severe) on the IGA, the arm 1 reported if 26/65 presence of 20 to 100 inflammatory lesions, 30 assessment of

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Study details Participants Interventions Outcomes and results Comments Source of funding to 150 non-inflammatory lesions (including the ADAP-topical + BPO- outcome was Galderma Research & nose), and up to 2 nodules on the face. A topical blinded Development (conflicts of urine pregnancy test was required for females Coded intervention: 5. Selective interest reported). at baseline and throughout the study. arm 2 reporting Analysis method Exclusion details ADAP-topical + BPO- Low Intention to treat or Participants with acne conglobata, acne topical 6. Overall bias fulminans, nodulocystic acne, or acne completers analysis Coded intervention: Some concerns ITT requiring systemic treatment. arm 3 Method of ITT imputation Number included Vehicle MI (no other details reported) Number randomised: arm 1 217 Number randomised: arm 2 217 Number randomised: arm 3 69 Number completed: arm 1 197 Number completed: arm 2 192 Number completed: arm 3 61 Study details N=174 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Stewart, D. M. T., H. M.,Weiss, Sex (weeks) arm 1 1. Randomisation J. S.,Plott, R. T.Dose-ranging mixed 12 3/59 Some efficacy of new once-daily age (mean±SD) Treatment duration Skin irritation (n/N): concerns;methods extended-release minocycline 17.7 category arm 2 not reported for acne vulgaris. 2006. Cutis; age (min/max) 12 to <24 weeks 2/60 2. Deviation from cutaneous medicine for the 17/19 Number of arms Skin irritation (n/N): intervention practitioner Low;double- Inclusion/exclusion criteria 3 arm 3 Trial ID blind;ITT Used validated acne scale Split face design 1/55 Stewart 2006 no No GI side effects (n/N): 3. Missing Country outcome data Acne scale Intervention: arm 1 arm 1 United States (efficacy) None MINO-oral 2mg/kg/day 14/59 Study type High;>20% Inclusion details Intervention: arm 2 GI side effects (n/N): RCT discontinued - Participants aged 12 to 30 years, weighing MINO-oral 3mg/kg/day arm 2 20/60 unclear how many

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Study details Participants Interventions Outcomes and results Comments Source of funding between 39.1 kg and 102.3 kg (86 to 225 Intervention: arm 3 GI side effects (n/N): were due to lack of Not reported (conflicts of Ib)..Diagnosed with moderate to severe facial PLC-oral arm 3 efficacy - or which interest reported). acne vulgaris; at least 20 and no more than Coded intervention: 18/55 arm they were in Analysis method 100 inflammatory facial lesions and <5 facial arm 1 4. Outcome Intention to treat or nodules or cysts..Females of childbearing MINO-oral measurement potential must have had a negative urine completers analysis Coded intervention: (efficacy) pregnancy test result (25 µg/mL sensitivity), be ITT arm 2 Low;described as using contraception and will to continue on Method of ITT imputation MINO-oral double-blind, contraception during the study..Participants or without further LOCF Coded intervention: parent/guardian consent provided. details arm 3 PLC-oral 5. Selective Exclusion details Treatment category reporting Participants sensitive to minocycline or any of Some concerns;not Oral antibiotics the components..Pregnancy..Males with facial reported if trial hair..Use of supplements containing protocol was aluminium, calcium, iron, or magnesium, or registered vitamin A..Prior history of complicating 6. Overall bias illnesses or medications. High Number included Number randomised: arm 1 59 Number randomised: arm 2 60 Number randomised: arm 3 55 Number completed: arm 1 na Number completed: arm 2 na Number completed: arm 3 na Study details N=141 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Mucosal or cutaneous Tool v2.0 Strauss, J. S. R., R. P.,Shalita, Sex (weeks) changes (n/N): arm 1 1. Randomisation A. R.,Konecky, E.,Pochi, P. mixed 20 35/46 Some concerns; no E.,Comite, H.,Exner, J. information about H.Isotretinoin therapy for acne: allocation

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Study details Participants Interventions Outcomes and results Comments Results of a multicenter dose- age (other information) Treatment duration Mucosal or cutaneous concealment response study. 1984a. Mean age 23.3,23.1 & 22.2 in the 3 groups (no category changes (n/N): arm 2 provided Journal of the American SDs reported) 12 to <24 weeks 41/46 2. Deviation from Academy of Dermatology Inclusion/exclusion criteria Number of arms Mucosal or cutaneous intervention Trial ID Used validated acne scale 3 changes (n/N): arm 3 High; study was Strauss 1984a no Split face design 46/49 double-blinded in Country Acne scale No Relapse follow up: arm the beginning; then "The protocol United States None Intervention: arm 1 1 design allowed Study type Inclusion details ISO<120.Daily<0.5 (0.1 12 participating RCT Participants with treatment-resistant, severe mg/kg daily for 140 days) Relapse follow up: arm participants to be Source of funding nodulocystic acne; minimum of 10 2 Intervention: arm 2 retreated with Not reported. inflammatory nodulocystic acne lesions at 12 ISO<120.Daily=0.5 (0.5 isotretinoin in an Analysis method least 4 mm in diameter on the face, back, or mg/kg daily for 140 days) Relapse follow up: arm chest..Off all treatment for at least 1 open study Intention to treat or Intervention: arm 3 3 beginning at least month..Female participants were required to completers analysis ISO=120.Daily=0.5 (1 12 8 weeks after the have negative pregnancy test within 2 weeks Completers mg/kg daily for 140 days) Relapse (n/N): arm 1 completion of the prior to starting treatment. Coded intervention: 19/46 first course of Exclusion details arm 1 Relapse (n/N): arm 2 therapy if optimal Not reported. ISO<120.Daily<0.5-oral 9/46 improvement (less Number included Coded intervention: Relapse (n/N): arm 3 than a 95% Number randomised: arm 1 arm 2 5/49 reduction in na ISO<120.Daily=0.5-oral lesions) had not Number randomised: arm 2 Coded intervention: been achieved in na arm 3 the first course." Number randomised: arm 3 ISO=120.Daily=0.5-oral No ITT analysis was done na Treatment category 3. Missing Number completed: arm 1 Oral isotretinoin 46 outcome data Number completed: arm 2 (efficacy) 46 Some concerns;6% Number completed: arm 3 withdrawals in 2 49 out of 3 arms; no reasons provided; no ITT 4. Outcome measurement

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Study details Participants Interventions Outcomes and results Comments (efficacy) Some concerns;not reported if assessment of outcome was blinded 5. Selective reporting Some concerns;not reported if trial protocol was registered 6. Overall bias High Study details N=121 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Tanghetti, E. A., W.,Solomon, Sex (weeks) arm 1 1. Randomisation B.,Loven, K.,Shalita, mixed 12 11/61 Some concerns;no A.Tazarotene versus age (mean±SD) Treatment duration Skin irritation (n/N): information tazarotene plus 20 category arm 2 provided clindamycin/benzoyl peroxide age (min/max) 12 to <24 weeks 6/60 2. Deviation from in the treatment of acne 12 Number of arms intervention vulgaris: a multicenter, double- Some Inclusion/exclusion criteria 2 blind, randomized parallel- concerns;Double Used validated acne scale Split face design group trial. 2006. Journal of blind but not clear no No drugs in dermatology if participants were Intervention: arm 1 Trial ID Acne scale blinded; no ITT TAZ 0.1% cream + Tanghetti 2006 None Vehicle gel 3. Missing Country Inclusion details outcome data Intervention: arm 2 United States Participants aged at least 12 years of age. (efficacy) Stable moderate to severe facial inflammatory BPO 5%/CLIND 1% gel + Study type High;Around 20% acne vulgaris (defined as 15 to 60 papules TAZ 0.1% cream RCT discontinued - plus pustules, 10 to 100 comedos, and no Coded intervention: insufficient Source of funding more than 2 nodulocystic lesions with a arm 1 Not reported (conflicts of information on maximum diameter of 5 mm). Washout TAZ-topical + Vehicle reasons interest reported). periods required: 2 weeks for topical acne Coded intervention: 4. Outcome Analysis method treatments, 30 days for systemic antibiotics arm 2 measurement Intention to treat or and investigational drugs, 12 weeks for (efficacy)

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Study details Participants Interventions Outcomes and results Comments completers analysis oestrogens/birth control pills if previously used BPO-topical + CLIND- Some concerns;not ITT for <12 weeks, and 6 months for oral retinoids. topical + TAZ clear Method of ITT imputation Exclusion details Treatment category 5. Selective not reported Participants with acne known to be resistant to Topical retinoids ± other reporting oral antibiotics. Pregnancy, breastfeeding or of treatment Some concerns;not childbearing potential and not using reliable reported if trial contraception. protocol was Number included registered Number randomised: arm 1 6. Overall bias 61 High Number randomised: arm 2 60 Number completed: arm 1 50 Number completed: arm 2 52 Study details N=171 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Tanghetti, E. D., S.,Green, Sex (weeks) arm 1 1. Randomisation L.,Ling, M.,Downie, mixed 12 4 Some concerns;no J.,Germain, M. A.,Kasteler, J. age (mean±SD) Treatment duration Skin irritation (n/N): information S.,Kircik, L.,Oefelein, M. 19.8±6.7 category arm 2 provided G.,Draelos, Z.Clinical evidence age (median) 12 to <24 weeks 2 2. Deviation from for the role of a topical anti- 17.2 Number of arms Skin irritation (n/N): intervention inflammatory agent in 2 arm 1 Some concerns;not comedonal acne: Findings age (min/max) Split face design 84 clear if participants from a randomized study of 12.1/45.7 No Skin irritation (n/N): or investigators dapsone gel 5% in combination Inclusion/exclusion criteria were blinded Intervention: arm 1 arm 2 with tazarotene cream 0.1% in Used validated acne scale (single-blinded TAZ 0.1% cream 86 patients with acne vulgaris. no study); ITT 2011. Journal of Drugs in Acne scale Intervention: arm 2 analysis was done DAP 5% gel + TAZ 0.1% Dermatology None 3. Missing cream Trial ID Inclusion details outcome data Tanghetti 2011 Males or females aged at least 12 Coded intervention: (efficacy) Country years..Stable, non-rapidly progressing facial arm 1 Some United States acne vulgaris characterised by the presence of TAZ-topical concerns;6% 50 to 100 inflammatory lesions (papules, discontinued (1

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Study details Participants Interventions Outcomes and results Comments Study type pustules), 25 to 100 facial non-inflammatory Coded intervention: participant for RCT lesions (open/closed comedones0, no more arm 2 inefficacy); ITT Source of funding than 3 facial nodules and/or cysts of diameter DAP-topical + TAZ- used; imbalanced Allergan Inc (conflicts of =1 cm..Females of childbearing potential were topical between arms interest reported). required to use reliable methods of birth Treatment category 4. Outcome control. Analysis method Topical non-retinoids ± measurement Intention to treat or Exclusion details other treatment (efficacy) completers analysis Participants with a skin disease or disorder Low ITT that might interfere with the diagnosis or 5. Selective assessments of acne vulgaris or who failed to Method of ITT imputation reporting comply with the protocol specified washout Some concerns;not LOCF periods for prohibited treatments..History of reported if trial clinically significant anaemia or protocol was haemolysis..Evidence of recent alcohol or drug registered abuse..Participants with a history of poor co- 6. Overall bias operation or non-compliance with medical Some concerns treatment or who failed to comply with specified procedures. Number included Number randomised: arm 1 85 Number randomised: arm 2 86 Number completed: arm 1 77 Number completed: arm 2 83 Study details N=210 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Tanghetti, E. A. K., L. Sex (weeks) arm 1 1. Randomisation H.,Green, L. J.,Guenin, mixed 12 0/68 Some concerns;no E.,Harris, S.,Martin, G.,Pillai, age (mean±SD) Treatment duration Skin irritation (n/N): information R.A Phase 2, Multicenter, 22.1332857142857±9.2005769230769214 category arm 2 provided Double-Blind, Randomized, age (min/max) 12 to <24 weeks 1/71 2. Deviation from Vehicle-Controlled Clinical 12 Number of arms Skin irritation (n/N): intervention Study to Compare the Safety 3 arm 3 Low;double- and Efficacy of a Novel 0/67 Tazarotene 0.045% Lotion and

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Study details Participants Interventions Outcomes and results Comments Tazarotene 0.1% Cream in the Inclusion/exclusion criteria Split face design Participant reported blinded; ITT Treatment of Moderate-to- Used validated acne scale No improvement (n/N): arm analysis was done Severe Acne Vulgaris. 2019. no Intervention: arm 1 1 3. Missing Journal of drugs in Acne scale TAZ 0.045% lotion 27/69 outcome data dermatology Evaluator's Global Severity Scale (EGSS) Intervention: arm 2 Participant reported (efficacy) Trial ID Inclusion details TAZ 0.1% cream improvement (n/N): arm Some Tanghetti 2019 concerns;10% Participants of any gender, race and ethnicity, Intervention: arm 3 2 Country aged 12 years or older..Participants with Lotion vehicle or cream 26/72 withdrawals - imbalanced United States moderate to severe acne; EGSS score of 3 vehicle (arms combined) Participant reported between arms Study type (moderate) or 4 (severe); 20 to 40 Coded intervention: improvement (n/N): arm RCT inflammatory lesions (papules, pustules, and arm 1 3 4. Outcome Source of funding nodules), 20 to 100 non-inflammatory lesions TAZ-topical 20/69 measurement (open and closed comedones), and 2 nodules (efficacy) Ortho Dermatologics funded Coded intervention: or less..Women of childbearing potential were Low;likely blinded Konic Limited's activities arm 2 required to have a negative urine pregnancy 5. Selective relating to the manuscript TAZ-topical (conflicts of interest reported). test at and agree to use a reliable method of reporting contraceptive during the study Coded intervention: Analysis method Some concerns;not period..Washout period of 1 month required for arm 3 Intention to treat or reported if trial participants who previously used prescription Vehicle completers analysis protocol was and over-the-counter acne treatments, and 6 Treatment category ITT registered months for systemic retinoids. Topical retinoids Method of ITT imputation 6. Overall bias Exclusion details LOCF Some concerns Not reported. Number included Number randomised: arm 1 69 Number randomised: arm 2 72 Number randomised: arm 3 69 Number completed: arm 1 65 Number completed: arm 2 63 Number completed: arm 3 61

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Study details Participants Interventions Outcomes and results Comments Study details N=327 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Thiboutot, D. J., M.,Rich, Sex (weeks) arm 1 1. Randomisation P.,Rist, T.,Rodriguez, D.,Levy, mixed 8 1 Some S.A randomized, parallel, age (mean±SD) Treatment duration Skin irritation (n/N): concerns;insufficie vehicle-controlled comparison 19.9 category arm 2 nt information of two erythromycin/benzoyl provided age (min/max) 6 to <12 weeks 3 peroxide preparations for acne 12/46 Number of arms Skin irritation (n/N): 2. Deviation from vulgaris. 2002. Clinical intervention Inclusion/exclusion criteria 4 arm 3 Therapeutics Low;Double blind; Used validated acne scale Split face design 0 Trial ID ITT no No Skin irritation (n/N): Thiboutot 2002 3. Missing Acne scale Intervention: arm 1 arm 4 Country outcome data Physician's Global Assessment BPO 5%/ERYTH 3% gel 0 United States (efficacy) (PGA)/Physician’s Global Acne Severity Score Intervention: arm 2 Skin irritation (n/N): Study type Low Inclusion details BPO 5%/ERYTH 3% jar arm 1 RCT 4. Outcome Males and females aged >12 years of Intervention: arm 3 124 measurement Source of funding age..Moderate to moderately severe acne; 15 Vehicle gel Skin irritation (n/N): (efficacy) Dermik Laboratories, US. to 80 facial inflammatory lesions, 20 to 140 arm 2 Intervention: arm 4 Low Analysis method facial comedones (not including the nose or Vehicle Jar 121 Intention to treat or 5. Selective nasolabial area), <2 nodules or cysts >5 mm, Coded intervention: Skin irritation (n/N): completers analysis reporting and a minimum Physician's Global Acne arm 1 arm 3 ITT Severity score of 1.5. 42 Some concerns;not BPO-topical + ERYTH- reported if trial Method of ITT imputation Exclusion details Skin irritation (n/N): topical protocol was Unclear Not reported. arm 4 Coded intervention: registered Number included 40 arm 2 6. Overall bias Number randomised: arm 1 BPO-topical + ERYTH- Some concerns 124 topical Number randomised: arm 2 Coded intervention: 121 arm 3 Number randomised: arm 3 Vehicle 42 Coded intervention: Number randomised: arm 4 arm 4 40 Vehicle Number completed: arm 1 Treatment category 115 Topical or combination

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Study details Participants Interventions Outcomes and results Comments Number completed: arm 2 110 Number completed: arm 3 33 Number completed: arm 4 35 Study details N=2813 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Participant reported Tool v2.0 Thiboutot, D. A., S.,Soto, Sex (weeks) improvement (n/N): arm 1. Randomisation P.Efficacy and tolerability of mixed 12 1 Some adapalene 0.3% gel compared age (mean±SD) Treatment duration 284/724 concerns;insufficie to tazarotene 0.1% gel in the 19.3 category Participant reported nt information treatment of acne vulgaris. provided on age (median) 12 to <24 weeks improvement (n/N): arm 2008. Journal of drugs in allocation 16.8 Number of arms 2 dermatology 215/724 concealment age (min/max) 4 Trial ID 2. Deviation from 12/70.2 Split face design Participant reported Thiboutot 2008 improvement (n/N): arm intervention Inclusion/exclusion criteria No Country 3 Low;Double blind; Used validated acne scale Intervention: arm 1 United States 211/711 ITT no CLIND 1.2%/BPO 2.5% Study type Participant reported 3. Missing Acne scale gel RCT improvement (n/N): arm outcome data Evaluator's Global Severity Scale (EGSS) Intervention: arm 2 Source of funding 4 (efficacy) Inclusion details CLIND 1.2% Arcutis Pharmaceuticals 55/333 Some Males and females of any race and ethnicity, Intervention: arm 3 (conflicts of interest reported). concerns;around aged 12 years or older..Moderate to severe BPO 2.5% 10% discontinued Analysis method acne vulgaris (a score of 3 or 4 on the EGSS); Intervention: arm 4 4. Outcome Intention to treat or presenting with 17 to 40 inflammatory lesions Vehicle completers analysis measurement (papules, pustules, and nodules), 20 to 100 Coded intervention: ITT (efficacy) non-inflammatory lesions (open and closed arm 1 Low Method of ITT imputation comedones), and 2 nodules or less..Women of BPO-topical + CLIND- 5. Selective LOCF childbearing potential were required to have a topical reporting negative urine pregnancy test and to agree to Coded intervention: Some concerns;not use an effective form of contraception during arm 2 reported if trial the study..Washout periods required: 1 month CLIND-topical protocol was for previous prescription and over-the-counter Coded intervention: registered acne treatments; for topical (face) and arm 3 systemic treatments: topical astringents and 6. Overall bias BPO-topical abrasives (1 week); topical antiacne products, Some concerns

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Study details Participants Interventions Outcomes and results Comments including soaps containing antimicrobials, Coded intervention: arm 4 Vehicle and known comedogenic products (2 weeks); Treatment category topical retinoids, retinol, and systemic acne Topical or combination treatments (4 weeks); and systemic retinoids (6 months). Exclusion details Not reported. Number included Number randomised: arm 1 797 Number randomised: arm 2 812 Number randomised: arm 3 809 Number randomised: arm 4 395 Number completed: arm 1 724 Number completed: arm 2 724 Number completed: arm 3 711 Number completed: arm 4 333 Study details N=1640 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Tyring, S. K., Kircik, L. H., Sex (weeks) arm 1 1. Randomisation Pariser, D. M., Guenin, E., mixed 12 28/767 Some concerns;no Bhatt, V., & Pillai, R.Novel age (mean±SD) Treatment duration Skin irritation (n/N): information Tretinoin 0.05% Lotion for the 20.5±7.31 category arm 2 provided Once-Daily Treatment of age (min/max) 12 to <24 weeks 1/783 2. Deviation from Moderate-to-Severe Acne 9/58 Number of arms intervention Vulgaris: assessment of 2 Low;Double- Efficacy and Safety in Patients blinded: ITT Aged 9 Years and Older. 2018. analysis was done

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Study details Participants Interventions Outcomes and results Comments Journal of drugs in Inclusion/exclusion criteria Split face design 3. Missing dermatology Acne scale No outcome data Trial ID None Intervention: arm 1 (efficacy) Tyring 2018 Inclusion details TRET 0.05% lotion Some Country Males and females of any race and ethnicity, Intervention: arm 2 concerns;more International aged 9 years and older..Moderate (EGSS Vehicle than 5% withdrawals - Study type score 3) to severe (EGSS score 4) acne Coded intervention: balanced between RCT presenting with 20 to 40 inflammatory lesions arm 1 (papules, pustules, and nodules), 20 to 100 arms Source of funding TRET-topical non-inflammatory lesions (open and closed 4. Outcome Dow Pharmaceutical Sciences, Coded intervention: comedones), and 2 nodules or less..Women of measurement US; Ortho Dermatologics arm 2 childbearing potential were required to have a (efficacy) funded Konic's activities Vehicle negative urine pregnancy test and to agree to Low relating to the manuscript Treatment category use an effective form of contraception during 5. Selective (conflicts of interest reported). Topical retinoids the study..Washout periods required: 1 month reporting Analysis method for previous prescription and over-the-counter Some concerns;not Intention to treat or acne treatments; for topical and systemic reported if trial completers analysis treatments: topical astringents and abrasives protocol was ITT (1 week); topical anti-acne products, including registered Method of ITT imputation soaps containing antimicrobials, and known 6. Overall bias MI MCMC comedogenic products (2 weeks); topical Some concerns retinoids, retinol, and systemic acne treatments such as hormonal or antibiotic treatments (4 weeks); and systemic retinoids (6 months). Exclusion details Not reported. Number included Number randomised: arm 1 819 Number randomised: arm 2 821 Number completed: arm 1 680 Number completed: arm 2 701

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Study details Participants Interventions Outcomes and results Comments Study details N=209 Interventions Results Cochrane RoB Reference Characteristics Treatment duration Skin irritation (n/N): Tool v2.0 Zouboulis Ch, C. D., Sex (weeks) arm 1 1. Randomisation L.,Decroix, J.,Maciejewska- mixed 12 7 Some concerns;No Udziela, B.,Cambazard, age group Treatment duration Skin irritation (n/N): information F.,Stuhlert, A.A multicentre, =25 years category arm 2 provided single-blind, randomized age (mean±SD) 12 to <24 weeks 1 2. Deviation from comparison of a fixed 18.6±3.2 Number of arms Skin irritation (n/N): intervention clindamycin 2 arm 1 Low; participants phosphate/tretinoin gel age (median) Split face design 104 were blinded; ITT formulation (Velac) applied 18 No Skin irritation (n/N): used once daily and a clindamycin age (min/max) arm 2 3. Missing lotion formulation (Dalacin T) 14/26 Intervention: arm 1 105 outcome data applied twice daily in the Inclusion/exclusion criteria CLIND 1%/TRET 0.025% gel (efficacy) topical treatment of acne Used validated acne scale Some Intervention: arm 2 vulgaris. 2000. British Journal no concerns;Withdraw CLIND 1% lotion of Dermatology Acne scale al imbalanced Trial ID Cook Coded intervention: between Zouboulis 2000 Inclusion details arm 1 groups,(5% vs Country Participants aged between 14 and 26 CLIND-topical + TRET- 13%) - mostly due Europe years..Moderate to severe acne vulgaris; topical to patient request. Study type scoring =3 on the Cook acne scale. Coded intervention: 4. Outcome RCT Exclusion details arm 2 measurement CLIND-topical Source of funding Use of tretinoin or antibiotic treatments for (efficacy) Yamanouchi Europe BV, The acne during the 4 weeks prior to study; use of Treatment category Some Netherlands. irritants such as salicylic acid and benzoyl Topical or combination concerns;Investigat Analysis method peroxide during the 2 weeks prior to study; or not blinded Intention to treat or required other medical interventions within 5 5. Selective completers analysis days of the study..Participants with skin reporting disorders likely to compromise drug Some concerns;not completers absorption, known or suspected reported if trial hypersensitivity to lincomycin, clindamycin or protocol was vitamin A derivatives..Participants who had registered changed or started use of contraceptives or 6. Overall bias use of Diane® within 3 months of the study. Some concerns Those who had participated in another clinical trial within 3 months of the study.

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Study details Participants Interventions Outcomes and results Comments Number included Number randomised: arm 1 104 Number randomised: arm 2 105 Number completed: arm 1 90 Number completed: arm 2 100 ADAP: adapalene; ALA-PDT: aminolevulinic acid photodymanic therapy; ALA-RED-PDT: aminolevulinic acid using red light photodymanic therapy; AZITH: azithromycin; BPO: benzoyl peroxide; CLIND: clindomycin; CPA: cyproterone acetate; DAPS: dapsone; DOXY: doxycycline; EE: ethinylestradiol; ERYTH: erythromycin; FU: follow up; ISO: isotretinoin; IPL: intense pulsed light; ITT: intention to treat analysis; LOCF: last observation carried forward; LYME: lymecycline; MAL DL: methyl aminolevulinate using daylight; MICO: miconazole nitrate; MINO: minocycline; MOT: motretinide; NAFL: fractional erbium glass laser; NOR: norfloxacin; PDL: pulsed dye laser; PLC: placebo; PDT: photodynamic; PT: photochemical; RCT: randomised controlled trial; SAR/SARE: sarecycline; SD: standard deviation; TAZ: tazarotene; TETRA: tetracycline; TRET: tretinoin

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