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. 2022 Nov;15(11):43–68.

TABLE 1.

Effectiveness and tolerability outcomes (all outcomes reported pertain to those at final follow-up visit unless otherwise stated)

AUTHOR, YEAR PATIENTS (N) TREATMENT(S) EFFECTIVENESS SAFETY STUDY LIMITATIONS
TOPICAL RETINOIDS
Cook-Bolden et al,57 2019 766 Tretinoin 0.05% lotion vs. vehicle lotion Lesion count

  • Mean % reduction in IL 60.1% and NIL count 53% in intervention group vs. 51.1% and 38.7% with vehicle

Treatment success

  • ≥2 grade reduction in EGSS achieved by 19.6% vs. 12.7%

 Tolerability

  • Common reported: application site pain, dryness, erythema, scaling, and burning

 Need to expand on blinding procedure in original trials; no clear exclusion criteria provided; post-hoc analysis; short duration of follow-up
Lain et al
2019,58 		1,640 Tretinoin 0.05% lotion vs. vehicle lotion Lesion count

  • Black/African-American male patients: mean % reduction in IL of 58.2% in tretinoin group vs. 52.1% in Caucasian male patients (P=0.346) vs. 41% in vehicle group (P=0.033) and reduction in NIL of 49.1% in tretinoin group vs. 45.9% in Caucasian male patients (P=0.522) vs. 24% in vehicle group (P=0.006)

  • Black/African-American female patients: mean % reduction in IL of 57.3% in tretinoin group vs. 56.2% in Caucasian female patients (P=0.879) vs. 52% in vehicle group (P=NR) and reduction in NIL of 49.3% in tretinoin group vs. 56.2% in Caucasian female patients (P=0.236) vs. 36% in vehicle group (P=NR)

Treatment success

  • Black/African-American male patients: achieved in 18.0% in tretinoin group vs. 15.4% in Caucasian male patients (P=0.522) vs. 10% in vehicle group

  • Black/African-American female patients: achieved in 23.0% in tretinoin group vs. 23.3% in Caucasian female patients (P=0.946) vs 15% in vehicle group

 Not all data reported separately for ethnic vs Caucasian patients
Tolerability

  • Treatment-related AEs more frequent in female (5.2%) vs male (10.6%) patients (P=0.008)

  • Application site dryness in 2.6% Black/African-American participants (all female)

  • Erythema and pruritus reported in 30–40% patients (all ethnicities)

Withdrawals

  • Treatment discontinued due to treatment-related AEs in 0.6% male vs. 2.5% female patients (NR according to ethnicity)

 Short duration of follow-up; ITT analysis; no clear exclusion criteria; post-hoc analysis; safety outcomes poorly reported according to ethnicity; inconsistent reporting of P values especially when statistical significance not achieved; very large numbers of Caucasian patients
Kubota et al,25 2012 66 4/52 of 1% clindamycin phosphate gel 2x/day and 0.1% adapalene gel 1x/day, then 4/52 0.1% adapalene 1x/day vs. 4/52 of 0.1% adapalene for 2/52 Lesion count

  • Reduction in mean IL and NIL counts from 11.6±0.8 to 6.9±0.7, and from 7.5±0.7 to 4.6±0.5, respectively

Treatment success

  • Decrease in mean acne severity score from 2.0±0.1 to 1.4±0.1 (P <0.05)

QoL

  • Total mean QoL score and mean scores of emotion and function domains improved significantly (P<0.05) from 41.5, 67.6, and 15.5 at baseline to 21.2, 29.7, and 7.2, respectively

 Local AEs

  • 60 subjects experienced 60 local AEs (erythema, scaling, pruritus, burning

  • Most local events were mild or moderate

Withdrawals:

  • No subject withdrawals due to AEs

 Small study size; short duration of follow-up
TOPICAL ANTIBIOTICS
Kawashima et al,38
2017		 607 BPO 2.5% vs. BPO 5% vs. placebo Lesion count

  • Median % reduction in IL for 2.5% BPO, 5% BPO, and placebo were 72.7%, 75.0%, and 41.7% (P<0.001), respectively

  • Median % reduction for TL for 2.5% BPO, 5% BPO and placebo were 62.2%, 67.9% and 28.6% (P<0.001)

  • Median % reduction in NIL for 2.5% BPO, 5% BPO and placebo were 56.5%, 68.2% and 21.9% (P< 0.001), respectively

 Percent of patients who experienced AEs

  • Incidence of AE with a possible causal relation was 37.3% for 2.5% BPO, 38.7% for 5% BPO, and 12.9% for placebo

  • No cases of death or severe AE

Local AEs

  • 2.5% BPO: skin exfoliation (19.1%), application site erythema (13.7%), application site irritation (8.3%), application site pruritus in (3.4%), contact dermatitis (2.5%)

  • 5% BPO: skin exfoliation (23.5%), application site irritation (12.3%), application site erythema (10.8%) , application site pruritus (2.5%)

  • Placebo: skin exfoliation (8.0%)

Withdrawals

  • 13 patients discontinued due to AE (6, 5, and 2 for 2.5% BPO, 5% BPO, and placebo, respectively)

 No patient satisfaction measures; short duration of follow-up; different denominator for efficacy (n=607) and AEs (n=609)
Kawashima et al,20
2017		 458 BPO 2.5% vs. BPO Lesion count

  • Mean % reduction in IL and NIL: 63.6% and 54.3% compared to 43.5% and 38.1% with vehicle (P=0.001 and P=0.008, respectively)

Treatment success

  • ≥2 grade improvement in EGSS achieved by 36.5% in C/BPO group vs. 28.3% in vehicle group (P=0.326)

 Treatment-emergent AEs

  • In C/BPO group, treatment-emergent AEs infrequent and unrelated to treatment (n=4, nasopharyngitis and headache); in vehicle group AEs considered related to treatment (n=2, facial pain, swelling of face)

Local AEs

  • Mild-to-moderate tolerability issues in C/BPO group

Withdrawals

  • No study withdrawals due to AEs

 Post-hoc analysis; unclear whether ITT used for all outcomes; no analysis of White vs. non-White patients
Alexis et al,59
2017		 136 Clindamycin phosphate 1.2%/BPO 3.75% vs. vehicle Lesion count

  • At 12 weeks, greatest reduction in median TLC, median IL count, and median NIL count in 2.5% BPO and 5% BPO groups, reductions of 62.1% vs. 66.9%, 68.2% vs. 72.7%, and 75% vs. 83.3%, respectively

  • At 52 weeks, median reduction in TLC in 2.5% and 5% BPO groups were 75.3% and 80.4%, respectively

Microbiology

  • Microbial assays carried out in 238/458 patients; Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) detected in 179 and 111 patients, respectively; assay repeated at Week 52 on 87 of remaining 393 participants; P. acnes and S. epidermidis detected in 65 and 39 patients, respectively.

 Percent of patients who experienced AE:

  • 84% in the 2.5% BPO group, 87.2% in the 5% BPO group, and 85.6% in total

  • 52.2% (239/458) AEs among entire study group had a possible causal relationship to BPO

  • AEs included skin exfoliation, local irritation, erythema, dryness, pruritis, contact dermatitis, xeroderma, blepharitis, erythema of eyeline, urticaria, intertrigo and eczema

Monitoring

  • No significant change in clinical laboratory tests in both groups.

 Post-hoc analysis; unclear whether ITT used for all outcomes; no analysis of White vs. non-White patients
Xu et al,26
2016		 1,016 Clindamycin phosphate 1%/BPO 5% vs. clindamycin only Lesion count

  • Mean % reduction in TLC 72% (C/BPO) and 67% (clindamycin) (P=0.003)

  • Mean % reduction in IL count 78% (C/BPO) and 75% (clindamycin) (non-significant) Mean % reduction in NIL count 67% (C/BPO) and 60% (clindamycin) (P=0.019)

Treatment success

  • Improvement of ≥2-grade in ISGA score achieved in 30.2% (C/BPO) vs. 22.7% (clindamycin) (P=0.018)

QoL measures

  • DLQI and CDLQI reduced from baseline in both treatment groups (DLQI total score: C/BPO -5.4 and clindamycin -4.7; CDLQI total score: C/BPO -4.1 and clindamycin -4.5)

 Percent of patients who experienced AE

  • Overall incidence of AEs higher in C/BPO group (14.4%) than in clindamycin group (7.9%)

  • Majority of AEs were mild-to-moderate intensity

  • Incidence of drug-related AEs was 8.6% in C/BPO group vs. 1.2% in clindamycin group

  • No deaths reported

Local AEs

  • Most common drug-related AE associated with C/BPO treatment was application site erythema, pruritus, and pain

Withdrawals

  • 16 patients discontinued study: 2.4% from C/BPO group and 0.8% clindamycin group, primarily due to application site reaction (swelling, erythema, and pruritus)

 Single blinding; short duration of follow-up; no placebo arm; sex numbers do not match to reported participants
Amar et al,63
2015		 20 Clindamycin phosphate 1.2%/BPO 2.5% gel Lesion count

  • Mean % reduction in IL count, NIL count and TLC of 76%, 62%, and 71% respectively (P<0.0002)

Treatment success

  • IGA reduced to "clear" or "almost clear" in 70% participants (P=0.0001), all patients experienced ≥1 grade improvement in IGA

  • PIH severity improved by ≥1 grade in 95% participants

 Number of patients who experienced AE

  • 10 participants experienced a total of 21 AEs

  • No serious AEs; only 1 AE possibly related to study drug (facial tattoo tightening), which resolved by end of study

Local AEs

  • Erythema, dryness, peeling, oiliness minimal at baseline and resolved within 4/52 of treatment

 Nonblinded study; no control arm; small population sample; short duration of follow-up; no definition of AEs provided
Kawashima et al,27 2015 800 Clindamycin phosphate 1.2% / BPO 3.0% OD vs BD vs clindamycin BD Lesion count

  • Mean TLC reduction of -57.5±26.7 in C/BPO OD group vs -60.4±34.6 in C/BPO BD group vs -48.9±34.9 in clindamycin BD group

Treatment success

  • ≥2-grade improvement in ISGA score achieved by significantly more patients from Week 4 with C/BPO 3.0% OD or BD than with clindamycin BD (P<0.05)

 Treatment-emergent AEs

  • Most AEs were mild or moderate in severity

  • Severe AEs occurred in two patients (erythema plus face swelling, and contact dermatitis) in C/BPO OD group

  • No deaths or serious AEs occurred

Local AEs

  • Issues of tolerability (dry skin, contact dermatitis, erythema, pruritus, skin exfoliation, skin irritation, eczema, facial pain, burning) higher for C/BPO OD (24.0%) or BD (35.1%) than for clindamycin BD (9.0%)

Withdrawals

  • Permanent discontinuations in 8.3% patients receiving C/BPO OD, 9.1% receiving C/BPO BD and 2.3% receiving clindamycin BD

 Short duration of follow-up; multiple analyses at various timepoints and between subgroups; single-blinding
Kawashima et al,39 2014 360 BPO 3% vs. vehicle Lesion count

  • Absolute reduction in TLC of -44.0±32.34 in BPO group vs. -22.2±34.02 in vehicle group (P<0.001)

  • Difference of adjusted mean absolute change -8.6 (95% CI, -11.1 to -6.2; P<0.001) for IL counts, and -12.3 (95% CI, -16.5 to -8.2; P<0.001) for NIL counts, in favor of BPO

Treatment success

  • ≥2-grade improvement in ISGA score achieved in significantly higher proportion of BPO (19%) group than with vehicle (1%) (P< 0.001)

 Percent of patients who experienced AE

  • Incidence of AE higher for BPO (58%) than for vehicle (47%)

  • All AEs were mild or moderate

  • No severe or serious AE or deaths reported

Local AEs

  • Drug reactions (facial pain, pruritus, dry skin, contact dermatitis, erythema, and skin irritation) more frequent for BPO (30%) than for vehicle (5%)

Withdrawals

  • Permanent discontinuation of 12 patients (7%) in BPO group vs. 5 patients (3%) in vehicle group

 Short duration of follow-up; no active comparator
Cook-Bolden et al,60 2012 458 Clindamycin phosphate 1.2%/BPO 2.5% vs. clindamycin only vs. BPO only vs vehicle Lesion count

  • Mean % reduction in IL counts of 71.6% (C/BPO), 57.1% (clindamycin only, P=0.001), 58.4% (BPO only, P<0.001), 47.6% (vehicle, P<0.001)

  • Lesion reduction in Hispanic population greater than in overall acne population

Treatment success

  • IGA of "clear" or "almost clear" in 33.1% of C/BPO group vs. 11.5% in vehicle group (P=0.003)

 Local AEs

  • No subjects experienced severe local signs or symptoms

  • Overall mean scores of 0 (none) for burning and stinging, and 0.1 for itching, scaling ,and erythema (where 1.0=mild) in C/BPO group

Withdrawals

  • No patient withdrawals due to AEs

 Post-hoc analysis; short duration of follow-up; FPS not reported (Hispanic may include White patients)
Callender VD,61 2012 797 Clindamycin phosphate 1.2%/BPO 2.5% vs. vehicle Lesion count

  • Median % reduction in IL, NIL, and TLC of 63%, 50%, and 52.4% in FPS I–III vs. 65%, 47%, and 51.4% in FPS IV–VI

Treatment success

  • EGSS of "clear" or "almost clear" of 29.8% in FPS I–III vs. 27.2% in FPS IV–VI

 Local AEs

  • No severe local AEs or symptoms

Tolerability

  • Mean scores for burning and stinging of 0 (none), 0.1 for itching and scaling, and 0.1 or 0.2 for erythema with no increased irritation in FPS IV–VI group

Withdrawals

  • No participants withdrew due to erythema, scaling, itching, burning, or stinging

 Post-hoc analysis; Comparisons made between FPS subgroups, with little mention of results from vehicle arm; Inclusion of patients with FPS I
Jung et al,40
2011		 34 1% nadifloxacin cream vs. vehicle cream Lesion count

  • Reduction in IL from 8.7±4.2 to 2.7±2.4 (P<0.001) with nadifloxacin cream vs. to 8.4±6.2 with vehicle

  • Reduction in NIL from 21.4±15.4 to 11.1±7.2 vs. to 18.6±8.6 with vehicle

Treatment success

  • Baseline acne severity grade of 2.69 decreased to 0.98 (P<0.001) and 2.44 (P=0.57) with nadifloxacin and vehicle cream, respectively

 Local AEs

  • Mild erythema (n=4) and dryness (n=2), which resolved spontaneously on nadifloxacin side

 Small study size; unclear enrolment process; short duration of follow-up
COMBINED TOPICAL RETINOID AND ANTIBIOTIC
DuBois et al,64
2019		 50 Adapalene 0.3%/BPO 2.5% Treatment success

  • 56% participants had IGA 0–1

  • 87% had good to excellent improvement in GAI

QoL

  • Participants reporting "no effect at all" of acne on QoL increased 15% to 55%, participants reporting "very large" to "extremely large effect" of acne on QoL reduced 28% to 4%; 75% satisfied or very satisfied with treatment effectiveness

 Percent of patients who experienced AE

  • 4% reported pruritus; 4% reported PIH change; 2% reported skin irritation; 2% reported cheilitis, eschar and papular rash

  • No serious or severe AEs

Withdrawals
No AEs leading to discontinuation		 Prospective, open-label design; Small number of patients; Single-arm study
Hayashi et al,28 2018 349 Clindamycin phosphate 1.2%/BPO 3.0% ON vs. clindamycin 1.2% BD/adapalene 0.1% ON Lesion count

  • Mean reduction in TLC, IL counts, and NIL counts after C/BPO or adapalene/clindamycin of -80.7±34.04 vs. -78.1±36.33, -27.2±11.02 vs. -25.6±11.71 and -53.5±28.4 vs. -52.5±31.46, respectively

Treatment success

  • ≥2-grade improvement in ISGA score achieved in 37% C/BPO vs. 27% adapalene/clindamycin

 Percent of patients who experienced AE

  • Overall incidence in C/BPO group (31%) lower than adapalene/clindamycin group (56%)

  • Most AEs were mild or moderate in severity

  • One serious AE (duodenal ulcers) unrelated to study treatment in C/BPO 3% group

Local AEs

  • Application-site dryness (24%), pain (9%), and erythema (6%) in adapalene/clindamycin group vs. application-site dryness (9%) and pruritus (3%) in C/BPO group

Withdrawals

  • 2% in both groups - all due to application-site events

 Single blinding; short duration of follow-up; no placebo arm; multiple subgroup analyses; variable reporting of P values
Alexis et al,62
2017		 286 Adapalene 0.3%/BPO 2.5% vs. vehicle Lesion count

  • Mean change in IL count in FPS I–III of -62.1% in A/BPO vs. -28.7% in vehicle group, in IV–VI group -63.7% vs. -45.0% in vehicle group (P<0.001)

  • Mean change in NIL count in FPS I–III of -63.6% in A/BPO group vs. -32.9% in vehicle group, in IV–VI group -61.1% in A/BPO group vs -34.0% in vehicle group (P<0.001)

 Percent of patients who experienced AE

  • Most common AEs in A/BPO group: nasopharyngitis (6.5%), skin irritation (4.1%)

Local AEs

  • Scores of "none" or "mild" for FPS I–III erythema (90.3% A/BPO vs. 92.3% vehicle), scaling (98.3% A/BPO vs. 100% vehicle), dryness (95.6% A/BPO vs. 100% vehicle), stinging/burning (99.1% A/BPO vs. 100% vehicle)

  • Scores of "none" or "mild" for FPS IV–VI erythema (100% A/BPO vs. 91.3% vehicle), scaling (97.5% A/BPO vs. 91.3% vehicle), dryness (98.2% A/BPO vs. 95.7% vehicle), stinging/burning (100% A/BPO vs. 100% vehicle)

 Post-hoc analysis; inclusion of FPS I patients and patients w/ darker skin types; multiple subgroup analyses
Kim et al,30 2013 23 Adapalene 0.1%/BPO 2.5% vs. Adapalene 0.1% Lesion count

  • Decrease in IL and NIL counts more remarkable on A/BPO side compared to adapalene side (5.9±2.5 and 4.9±3.2 vs. 13.1±7.1 and 9.7±4.1, respectively) (P=0.023)

 Local AEs

  • Erythema 8.7% both sides, scaling 17.4% A/BPO vs. 13.0% adapalene, dryness 13.0% A/BPO vs. 8.7% adapalene, stinging/burning 4.3% both sides

 Small study size; short duration of follow-up; single-blinded study; no ITT analysis
Takigawa et al,31 2013 188 Adapalene 0.1%/nadifloxacin 1% vs. adapalene 0.1% monotherapy Lesion count

  • Mean reduction in IL count 66% adapalene/nadifloxacin group vs. 51% adapalene group (P=0.0056)

Treatment success

  • Excellent or good therapeutic effect 73.8% adapalene/nadifloxacin group vs. 59% adapalene group (P=0.02496)

 Local AEs

  • No systemic AEs

  • Dryness and burning most frequently reported local effects and mostly mild

Withdrawals

  • 1 patient in adapalene/nadifloxacin group withdrew due to severe skin irritation

 No exploration of limitations within manuscript; per-protocol analysis rather than ITT; short duration of follow-up; no placebo group
Callender et al,41 2012 33 Clindamycin phosphate 1.2%/tretinoin 0.025% vs. vehicle Lesion count

  • Mean IL count reduced 5.5±6.56 clindamycin/tretinoin group vs. 4.1±11.36 (P=0.05) vehicle group

  • Mean NIL count reduced 21.3±22.60 clindamycin/tretinoin group vs. 12.8 (±40.08) (P=NS) in vehicle group

Treatment success

  • EGSA of 0 or 1 ("clear" or "almost clear") 47% clindamycin/tretinoin vs. 27% (vehicle) (P=NS)

  • ≥1-point improvement in PGA score 80% clindamycin/tretinoin and 53% vehicle

 Local AEs

  • Severity scores 0 or 1 reported in 85–100% patients for scaling, erythema, burning, stinging, itching

Withdrawals

  • Periorbital edema of moderate severity possibly related to clindamycin/tretinoin gel

 Small sample size; short follow-up period; use of cleansing bar and sunscreen as potential confounders; inconsistent reporting of P values
Schmidt et al,42 2011 2,010 Clindamycin phosphate 1.2%/tretinoin 0.025% vs. clindamycin only Lesion count

  • Mean % decrease in lesion counts >clindamycin/tretinoin group (range: 46.9–67.1%) vs. clindamycin group (range: 36.8–59.1%) for all FPS

 Local AEs

  • AEs not reported according to FPS

  • Investigator-based evaluations: clindamycin/tretinoin group exhibited >scaling and dryness than participants in clindamycin-only arm

  • Erythema scores for both groups were similar

  • No reports of hypo- or hyper-pigmentation

 Limitations not explored; unclear where study conducted (multicenter sites not stated); short duration of follow-up; AEs not presented according to FPS
TOPICAL DAPSONE
Taylor et al,43
2018		 4,327 Dapsone 7.5% vs. vehicle Lesion count

  • Percent reduction in IL count FPS I–III -54.2% dapsone group vs. -46.1% vehicle group; FPS IV–VI -56.0% dapsone group vs. -51.1% vehicle group (P≤0.01)

  • Percent reduction TLC FPS I–III -48.8% dapsone group vs. -41.2% vehicle group; FPS IV–VI -49.6% dapsone group vs. -45.2% vehicle group

Treatment success

  • ≥1 grade improvement in GAAS achieved in FPS I-III 76.6% in dapsone group vs. 62.8% in vehicle group (P<0.001); in FPS IV–VI 76.6% dapsone group vs. 67.9% vehicle group (P<0.001)

 Percent of patients who experienced AE

  • Safety population (n=432)— similar rate of treatment-related AEs, serious AEs, and AEs leading to discontinuation (treatment-related AEs: 3.4% vs. 3.5% FPS I–III; 3.6% vs. 3.3% FPS IV–VI; serious AEs: 0.3% vs. 0.5% FPS I–III; 0.4% vs. 0.3% FPS IV–VI)

Local AEs

  • Similar rates of investigator-reported erythema and scaling and patient-reported stinging/burning across 2 subgroups, typically mild in severity

Withdrawals

  • AEs leading to discontinuation: 0.4% vs. 0.4% FPS I–III; 0.2% vs. 0.2% FPS IV–VI

 Post-hoc analysis; short duration of follow-up; inconsistent use of P intervals and standard error
Draelos et al,44 2017 1,850 Dapsone 7.5% gel OD vs. vehicle Lesion count

  • Mean % change in IL count (-57.6% dapsone group vs. -53.0% vehicle group); NIL count (-48.6% dapsone group vs. -43.5% vehicle group); TLC (-51.9% vs. 47.0%)

 Percent of patients who experienced AE

  • 16.7% dapsone group vs .15.2% vehicle group

Local AEs

  • Dryness 1.6% dapsone vs. 1.3% vehicle, pruritus 1.5% dapsone vs. 0.6% vehicle, erythema 0.4% dapsone vs. 0.7% vehicle, pain 0.8% dapsone vs. 1.5% vehicle

 Post-hoc analysis of PIH outcomes; short duration of follow-up; complete inclusion/exclusion criteria from original studies not reported; inconsistent P value reporting
Alexis et al,53
2016		 67 Dapsone 5% Lesion count

  • TLC reduced 52%

Treatment success

  • Mean change in GAAS: -1.2 (95% CI, -1.4, -1.0, P<0.001)

 Percent of patients who experienced AE

  • 20.6% reported ≥1 AE

  • No AE considered treatment-related

  • One serious AE (spontaneous termination of pregnancy) but considered unrelated to treatment

Local AEs

  • Burning (1.6%), erythema (9.5%), dryness (15.9%), peeling (11.1%), oiliness (11.1%)

 Different number of patients included for data analysis at different time points; small sample size; short study duration; open-label; no control arm
CHEMICAL PEELS
How et al,45 2020 36 Jessner's solution peel vs. SA 30% peel Lesion count

  • Significant reduction in IL in both treatment arms (SA: 1.5; JS: 2) (P<0.001)

  • Significant reduction in NIL in both treatment arms (SA:5.5; JS:6) (P<0.001)

Treatment success

  • Significant reduction in Michaelsson Acne Score in both treatment arms (SA: 5.5; JS: 6) (P<0.001)

  • Significant reduction in PAHPI in both treatment arms (SA:6; JS:6) (P=0.003 [SA]), P<0.001 [JS])

 Local AEs

  • No systemic AEs reported

  • Burning, stinging immediately after application reported after almost all treatments

  • Exfoliation 36.3% SA arm vs. 44.1% JS arms

  • Other commonly reported local AEs: acneiform eruption (2 mild, 3 moderate, 1 severe)

  • One case prolonged erythema and PIH JS arm; 5 cases post-peel erythema SA arm v.s 4 JS arm

 Small sample size; short duration of follow-up; ITT and per-protocol analysis performed
Sarkar et al,21
2019		 45 35% GA peel vs. 20% SA + 10% mandelic acid peel vs. phytic acid peel Lesion count

  • Percent improvement comedones 56.32% GA; 62.4% SA+mandelic acid; 44.9% phytic acid

  • % improvement papules 69.88% GA; 70.09% SA+mandelic acid; 67.0% phytic acid

  • % improvement pustules 72.5%GA; 95.84% SA+mandelic acid; 68.33%phytic acid

 Local AEs

  • All peels were well tolerated

  • 13.3% in GA & SA+mandelic acid groups reported burning vs. 0% in phytic acid group

  • 6.7% in SA+mandelic acid reported postprocedural erythema that subsided within 2 days

Withdrawals

  • No withdrawals due to AEs

 Small sample size; short duration of follow-up; evaluator bias due to subjective nature of scoring system; inconsistent reporting of P values; nonspecified population other than "Asian"
Kaminaka et al,46 2014 25 40% GA peel vs. placebo peel Lesion count

  • Statistically significant reduction in IL, NIL, and TLC between GA side and placebo side (P<0.01) (no raw data available)

Treatment success

  • Overall therapeutic effect "excellent" or "good" for n=23 (92%) GA side; n=10 (40%) placebo side

 Local AEs

  • No significant AEs (bullae, swelling, pigmentary complications, scarring)

  • No systemic AEs

  • Most patients reported transient post-treatment mild erythema that lasted a few minutes

  • Mild dryness (GA n=7; placebo n=25); scaling (GA n=4; placebo n=3)

Withdrawals

  • No withdrawals due to AEs

 Small sample size; short duration of follow-up; raw data unavailable
PHOTODYNAMIC THERAPY
Choi et al,22
2018		 21 ICG-PDT w/ either LED 830nm or diode laser 805nm Lesion count

  • After avg 3.8 sessions ICG-LED group: NIL reduced 30.5±4.34 to 16.7±1.18, IL reduced 13.5±1.82 to 7±8.86 vs. after avg 3.3 sessions ICG-diode laser group: NIL reduced 31.4±5.94 to 14.7±10.58, IL reduced 14.1± 8.40 to 6.5± 6.36

Treatment success

  • After avg 3.8 sessions ICG-LED group: mean pretreatment KAGS 3.39±1.1 reduced to 2.31±1.11 vs. after avg 3.3 sessions ICG-diode laser group: mean pretreatment KAGS 3.38± 0.92 reduced to 2.13±0.99

 NR Unclear inclusion criteria on acne severity; no details on PDT parameter settings, number of passes or duration; no detail on interval length between treatment or follow-up period; no details on methods of statistical analysis
Mokhtari et al,23 2017 58 BPO 5% + 570nm IPL vs. BPO 5% only Lesion count

  • Significant reduction TLC 41.86±14.17 to 6.95±6.81 BPO-IPL group vs. 44.83±25.36 to 19.65±9.11 BPO only group (P<0.0001)

Treatment success

  • Significant reduction AGSS 3.34±0.67 to 0.93±0.84 BPO-IPL group vs. 3.38±0.68 to 2.17±0.83 BPO only group (P<0.0001)

  • Significant reduction ASI 37.47±16.67 to 5.43±6.16 BPO-IPL group vs. 42.95±41.08 to 17.98±11.02 BPO only group (P<0.0001)

 Local AEs

  • BPO-IPL treatment well tolerated

  • After BPO-IPL, 6 patients reported erythema; 4 patients reported pain

Withdrawals:

  • 2 patients withdrew due to intolerable erythema in BPO-IPL group

  • 4 patients withdrew in BPO only group due to erythema or skin scaling

 Small sample size; nonblinding of participants and assessors; per protocol analysis; patients who were sensitive to BPO omitted several doses and recommenced at a lower dose, which introduces heterogeneity of intervention
Ma et al,65
2015		 21 ALA 5% + LED 633nm Lesion count

  • Significant reduction IL (papules, pustule, nodules/cysts, P<0.05 or P< 0.01) compared to NIL (comedones, P >0.05); no raw data available

Treatment success

  • Total effective rates (Grades 0+1+2+3/total cases x 100%) 85.71%, 90.48%, 95.23%, respectively, after 3 PDT sessions

 Local AEs

  • No serious AEs (ulceration, infection, purpura, scarring)

  • Pain at start of irradiation (n=19/21), post-treatment edematous erythema (n=15/21), mild desquamation (n=5/21), temporary hyperpigmentation (n=8/21) that resolved within 1–3 months without intervention

 Small sample size; short follow-up period; no control group
Dong et al,54
2016		 46 ALA 10%+543–548nm, and 630±6nm LED Lesion count

  • 48.83% patients achieved ≥90% lesion clearance; 41.30% achieved 60–89% clearance; 8.70% achieved 30–59% clearance; 2.17% achieved <29% clearnace

  • No significant difference in therapeutic effectiveness between participants receiving 2 or 3 sessions

Patient Satisfaction

  • 95% participants satisfied or very satisfied with improvement in acne

  • No subject reported that acne had become worse

 Local AEs

  • Generally well tolerated

  • No new pustules, vesicles, desquamation, exfoliation, or scarring

  • Most patients experienced slight or moderate erythema and edema immediately following ALA-PDT, subsided within 1–2 days

  • 65.22% reported mild pain, 34.78% reported moderate-to-severe pain

  • Visible mild-to-moderate hyperpigmentation in 15.22%, but resolved within 1–2 months after last treatment session without further intervention

 Small sample size and short duration of follow-up; single-blinded study; variable endpoint; unclear how patient satisfaction measured
Park et al,49
2015		 1213 ICG-IPL-PDT Treatment success

  • 76–100% lesion reduction achieved in 483 (39.8%) patients; 0–50% lesion reduction) achieved in 730 (60.2%) patients

Patient Satisfaction

  • 16.3% highly satisfied, 73.1% somewhat satisfied, 10.6% unsatisfied

 Local AEs

  • Treatment well tolerated

  • Reported side effects: pain, erythema, scales, pruritis (resolved without treatment within 7/7)

 Subjective bias due to use of nonvalidated tools; results do not state proportion of patients who had 3, 4, or 5 sessions; no statistical analysis; inconsistent intervention
Tao et al,52
2015		 136 ALA+LED 633±3nm Treatment success:

  • 4/52 after final treatment: total effective rate (number of cases cured + number of cases with excellent response/total cases x 100 i.e., ≥60% clearance) of 92.65%

 Local AEs

  • Erythema (n=94), edema (n=2), pain (n=53), desquamation (n=12), slight-to-moderate hyperpigmentation (n=21), exudation (n=4)

 Skin was cleansed, oily crusts removed, fluctuant cysts aspirated, and comedones extracted in addition to the study intervention prior to the second and third treatment; reporter bias due to nature of study; short duration of follow-up
Song et al,32 2014 24 Chlorophyll-a+430±10nm & 660±10nm LED vs. LED monotherapy Lesion count

  • Pustule count: chlorophyll-a+PDT reduced from 3.8 at baseline to 1.3 (66% improvement; P<0.001) vs. LED 4.2 at baseline to 3.0 (29% improvement; (P<0.001)

  • Nodules and cysts: no statistically significant difference between 2 treatments

Treatment success

  • Mean acne grade on chlorophyll-a+PDT side was 1.8 vs. 2.2 on LED-only side (P=0.02)

  • Histopathology (on chlorophyll-a+PDT side only)

  • Decrease of dermal pilosebaceous units and perivascular inflammatory cell infiltrates; increase of normal-appearing epidermis

 Local AEs

  • Tolerable in all cases—no pain, burning, itching, or PIH

 Small sample size; single-blinded; histology performed on intervention side only; no chlorophyll-a–only arm
Liu et al,24
2014		 150 ALA 5%+633nm LED vs. monotherapy w/IPL 420nm vs. LED 415±5nm & 633±6nm Lesion count

  • Mean number of sessions required to achieve ≥90% clearance: 3±1.52 PDT group; 6±2.15 PL group (P< 0.05); 9±3.34 in LED group (P< 0.01)

Treatment success

  • Clearance (≥90% lesion reduction) or moderate improvements (60-89% reduction) achieved in significantly more patients in PDT group: 92% in PDT group vs. 58% in IPL group (P<0.01) and 44% in LED group (P<0.01)

 Number of patients who experienced AE

  • In PDT group, 2/50 patients experienced hyperpigmentation that resolved after 1 month

Local AEs

  • Mild-to-moderate pain, erythema, and edema reported after every PDT treatment by 46 out of 50 patients

 Ethical approval not explicitly stated; nonblinded study; short duration of follow-up
Asayama-Kosaka et al,55
2014		 11 5% ALA+broadband light 600–1100nm Treatment success

  • Avg GAGS reduced from 22.1±3.8 to 19.48 after 1 month, and to 16.3 after 3 months

  • # patients w/ moderately severe acne decreased from 7 to 0 after 3 months

  • # patients w/ mild acne increased from 4 to 11 after 3 months

 Local AEs

  • 10/11 experienced some local side effects during or after PDT

  • Erythema in 10/11 pts

  • No PIH

  • 3/11 reported minimal pain

 Unclear duration of light therapy; small sample size; no SD given for GAGS scores at 1m and 3m
Ma et al,66
2013		 397 ALA+LED 633nm for 3–4 sessions Treatment success

  • Total effective rate 82.1% (# cases cured + # cases w/ excellent response/total cases x 100 i.e., ≥60% clearance)

  • No statistical significance in total effective rate between 3-session (80.2% )and 4-session (85.9%) groups (P>0.05)

 Local AEs

  • Erythema: 23.9%, mostly mild-moderate(n=12 severe erythema); edema 11.3%; pain 6.8%; mild-to-moderate desquamation 3.3%; slight-to-moderate transient pigmentation 2.3%; transient exacerbation of acne lesions 1.5%; moderate exudation (0.5%)

 Non-randomisation; short duration of study
Hong et al,33
2013		 20 MAL+red light vs. MAL+IPL 530–750nm Lesion count

  • Mean reduction IL: 69.5% red light side vs. 72.0% IPL side (P<0.05)

  • At 2/52, reduction IL: 26% red light side vs. 17% IPL side (P=0.008)

  • At 8/52, reduction TLC: 48.7% red light side vs. 52.5% IPL side (not significant; p value not reported)

  • No significant difference in IL or NIL counts between 2 treatments

 Local AEs

  • No difference in AEs between 2 sides of face

  • 1 patient developed considerable erythema and inflammation on red light side after irradiation, despite dose reduction; in this patient PDT on IPL side did not show any erythema or hyperpigmentation

 Single-blinding only; no placebo arm; small sample size; no ITT analysis; unclear randomisation process
Mei et al,34
2013		 41 ALA 10%+IPL 420–950nm vs. topical placebo+IPL 420–950nm Lesion count

  • Significant reduction mean IL count: from 31.1±3.8 to 5.0±1.3 ALA-IPL group vs. 28.2±4.1 to 8.2±1.7 placebo-IPL group (P< 0.05)

  • Significant reduction mean NIL count: from 31.1±7.1 to 14.0±6.2 ALA-IPL group vs. 28.2±4.1 to 18.6±3.1 in placebo-IPL group (P< 0.05)

 Local AEs

  • No vesiculation, desquamation, crust formation, or pigmentation in IPL+ALA (study group) or IPL (control group)

  • All patients described a burning pain during IPL and hot flush after illumination

  • 3 patients in ALA+IPL group developed transient erythema and monomorphic acneiform eruptions 24h after each treatment, resolved spontaneously in 1–2 days

 Blinding of participants only; limited sample size and short duration of follow-up; unclear whether other treatments coadministered during trial period
Wang et al,67
2012		 30 ALA 3, 5, or 10%+633nm-LED Treatment success

  • Similar responses in areas receiving either 3, 5, or 10% ALA

  • Poisson regression analysis: no significant change in lesion count for a 1-unit increase in ALA dose 0.999 times (95% CI 0.998–1.000, P=0.22)

 Local AEs

  • Pain during light irradiation, edema and erythema post-irradiation, epidermal exfoliation after 2–3 days requiring no intervention, mild pigmentation in 2 patients, and severity unrelated to dose of ALA

Withdrawals

  • 3/55 withdrawals due to pain

  • Recurrence in 4 patients at 3–5 months post-intervention

 55 patients recruited; results report outcomes for 30 patients only, but some AEs reported out of 55; unclear how moderate-severe acne determined; no validated tools used for primary outcomes; unclear timepoint for outcome measures
An et al,74
2011		 13 0.5% liposome-encapsulated 5-ALA+IPL 400–720nm Lesion count

  • Mean reduction in lesion count at 4/52: 43.2%

Treatment success

  • After 2 sessions, 23.1% patients showed 1-grade improvement in KAGS severity, 38.5% showed 2-grade improvement, 7.7% showed 3-grade improvement, 30.8% showed no change

 Local AEs

  • No bacterial or viral infections

  • No serious AEs (stinging or burning sensation, erythema, edema, hyperpigmentation, atrophy, or scarring)

 No control arm; small number of patients and short duration of follow-up; inconsistent statistical analysis; no randomization
IPL
Mohanan et al,69 2012 8 IPL IFL i200 system Treatment success

  • Avg # treatment sessions per patient: 3.4

  • 7 patients had good response to treatment (51–75% reduction in lesion count) and 1 patent had moderate response (25–50% reduction)

Patient Satisfaction

  • 87.5% patient satisfaction with IPL

 Local AEs

  • Two patients developed transient erythema after procedure, resolving spontaneously in a few hours

  • No other AEs

 No follow-up reported; small sample size; no control arm; inconsistent reporting of statistical significance; no randomization; inconsistent #. treatments across participants
El-Latif et al,68
2014		 50 IPL 530nm vs. 5% BPO Lesion count

  • Mean reduction of lesions after 5th session: IPL group 61.56%±26.14 vs. BPO group 69.40%±22.35 (P=0.06)

 Local AEs

  • All patients in BPO group, except for one, suffered from burning and irritation during study period.

  • In IPL group, 1 patient suffered burning sensation (increased photosensitivity) after sun exposure, lasting for 2 hours

 No randomisation; no control arm; statistical significance inconsistently reported; small sample size and short duration of follow-up; unclear if ethical approval obtained
Lee GS,70
2012		 18 IPL 420nm Treatment success

  • All patients showed some improvement

  • Grade 5 (total clearance): 0 patients; Grade 4: 5/18 patients; Grade 3: 8/18 patients; Grade 2: 4/18; and Grade 1: 1/18

  • 14/18 subjects (78%) had clearance ≥60%

 Local AEs

  • No serious AEs (including secondary hyperpigmentation)

  • Very mild erythema in all patients, resolved spontaneously within 24–48 hours

 Results for 1 vs. 2 sessions not reported separately; range of follow-up times; no control arm; no measures of statistical significance
LED
Kwon et al,47
2013		 35 LED 420nm blue light and 660nm red light vs. sham device Lesion count

  • Decrease in IL and NIL counts by 76.8% (22.8–5.3, P<0.01) and 54% (51.2–23.7, P<0.01), respectively, in IPL group

  • No significant difference in control group in IL and NIL counts (P>0.05)

Treatment success

  • No patients with IGA Grade 0 or 1 at baseline for both groups, 9 patients improved to Grade 1 and 5 patients to Grade 0 in treatment group (n=18); 2 patients improved to Grade 1 in control group (n=17)

 Local AEs

  • Mild dryness (n=2), mild erythema and desquamation (n=1) in LED group

 Unclear enrollment process and inclusion criteria; variable duration of LED use/day per patient despite regular adherence checks; small sample size; short duration of follow-up
LASERS
Kang et al,35
2019		 9 Laser one pass 1319nm and one pass 589nm Lesion count

  • 85.7% patients achieved reduction in TLC

  • Final follow-up 5.4 weeks after final treatment: IL reduced by 2.5 (-23.1%) on treatment side and increased 1.1 (+11.1%) on control side

  • Increased acne counts on both sides of face in 2 patients

 Local AEs

  • Mild discomfort (n=5) and moderate discomfort (n=3) during treatment

 Small sample size; short follow-up, unable to assess sustainability of results; no reporting on number of acne lesions; no statistical significance reported; single-blinded
Kwon et al,29
2018		 25 1450nm diode laser in dual mode vs. 1450nm diode laser in high energy mode Lesion count

  • Mean IL count decreased by 63.5% (13.6 to 5) on dual-mode side and 39.3% (12.3 to 7.5) on stamp mode-only side (P<0.05)

Treatment success

  • Mean Leeds Revised Scale from 3.9±0.9 to 1.9 for dual-mode side vs. to 2.7 for stamp-only side (P<0.05)

 Local AEs

  • Less erythema and edema with dual mode (P<0.05)

  • Localized pigmentation in 4 cases of stamp-only mode

  • No PIH in dual-mode regimen group

  • Lower pain score in dual mode than stamp-only mode groups (3.2±1.5 vs. 6.5±2.3, P<0.05)

 Single blind; small study group; short follow-up period
LASERS AND SYSTEMIC TREATMENT
Li et al,36
2021		 47 IPL 420nm +isotretinoin 0.5–0.75mg/kg/day Lesion count

  • Significant reduction in TLC: 51%±34.3 in isotretinoin+IPL group vs. 27.4%±12.7 in isotretinoin-only group (P<0.01)

Treatment success

  • Significant GEA reduction from 2.8±0.7 to 1.8±0.8 in isotretinoin+IPL group vs. 2.7±0.7 to 2.3±0.4 in isotretinoin-only group (P<0.05)

QoL

  • Significantly lower average DLQI in isotretinoin+IPL group (4.7±2.2), compared to isotretinoin-only group (6.3±1.9) (P<0.05)

 Local AEs

  • No severe AEs (ulceration, infection, depigmentation, atrophy, or scarring)

  • Isotretinoin+IPL group: mild erythema post-IPL, 1 patient with 1cm blister

  • Both groups: skin dryness, peeling lips, reaction to coadministered adapalene 0.1% gel

 Other topical agents also used in both groups (adapalene 0.1% gel and fusidic acid 2% cream); limited sample size and short duration of follow-up; single-blinded study
FMR
Kwon et al,37
2018		 26 FMR w/ 0.8mm and 2.0mm penetration depth and 20–50 intensity vs. 1450nm diode laser Lesion count

  • Decrease in IL count by 39.3% (from 14.5 to 9.5) on DL side, and 58.2% (from 15.6 to 6.0) on FMR side (P<0.05)

  • Decrease in NIL count by 27.5% (22.8 to 16.5) on DL side and 33.2% (23.1 to 15.4) on FMR side (P<0.05)

Treatment success

  • Leeds Revised Acne Grade decreased to 3.1 on DL side and 2.0 on FMR side

 Local AEs

  • No significant difference in post-treatment erythema and edema (P>0.05) between treatment groups

  • No PIH on FMR side, but 2 cases of mild, localized PIH on DL side

 Single blinded; short follow-up time; no control arm
Lee et al,71
2013		 20 FMR w/ 1.0mm or 1.5mm penetration depth for 50ms, or 100ms Lesion count

  • Mean TLC reduced from 18 at baseline to 14.1 at Week 2, but subsequently increased to 19.6 (Week 4) and 17 (Week 8)

  • # IL not significantly different between right and left cheeks

Treatment success

  • Acne severity mean scores: 1.8, 1.3, and 0.6 at Weeks 2, 4, and 8, respectively

  • Facial oiliness mean scores: 2.2, 1.9, and 1.7 at Weeks 2, 4 ,and 8 respectively

 Local AEs

  • No serious AEs, including secondary infection, scarring, or hyper/hypo-pigmentation

  • More pain and post-treatment crusting on right cheek associated with longer RF exposure time

  • Mild pain during treatment

  • Post-therapy bleeding, erythema, and edema improved within 1 week

  • 2 patients experienced mild multiple pin-head sized pustular eruptions (self-resolved)

 No control group; small sample size; no histological assessment of sebaceous gland; only one session of treatment
Lee et al,50
2012		 18 FMR w/ 3.0mm penetration depth and 7 intensity Treatment success

  • GIS for active inflammatory lesions—18 patients: Grade 4 (>75% improvement); 8 patients: Grade 3 (51–75% improvement); 6 patients: Grade 2 (26–50% improvement); 2 patients: Grade 1 (0–25% improvement)

 Local AEs

  • Pain during treatment, post-treatment crusting and scaling, edema, post-therapy edema, and oozing

  • Post-treatment bleeding, crusting, and scaling improved in 5 out of 7 patients without treatment.

 Single blinded; no statistical analysis to determine significance; retrospective assessment from photographs: subjective bias and difficult to assess true skin pattern
Suh et al,72
2021		 12 Topical gold nanoparticles plus 400nm tip photopneumatic device Lesion count

  • Avg # pustules decreased from 6.50 (assessor A) and 8.00 (Assessor B) to 2.17 (A) and 2.50 (B) after treatment (P=0.001)

  • Avg # papules decreased from 12.42 (Assessor A) and 13.33 (Assessor B) to 6.42 (A) and 6.50 (B) (P<0.001)

  • Avg # comedones decreased from 29.75 (Assessor A) and 27.33 (Assessor B) to 10.33 (A) and 11.58 (B) (P= 0.001)

Histopathology:

  • Decrease in inflammatory cell infiltration and fibrotic changes of the dermis

 Local AEs

  • No serious AEs

 No control arm; No objectively measured values; Small population size; Short duration of follow-up; Variation of assessment parameters between assessors
SYSTEMIC THERAPIES
Gan et al,51
2012		 2,255 Oral isotretinoin Treatment success

  • Majority (93.9%) of patients achieved complete remission or substantial improvement (not defined); OR for achieving complete remission 3.85 (95% CI: 2.68–5.55) for those who took ≥100 mg/kg of isotretinoin compared to those who took less

  • On average, patients received 7.8 months of treatment at a mean dose of 0.5mg/kg (SD±0.2) and mean total cumulative dose was 95.6mg/kg (SD±40.0)

 Local AEs

  • Isotretinoin generally well-tolerated

  • Among documented side-effects, cheilitis was the most common (64.8%, n=1,461), followed by headache (1.8%, n=41), mood change (1.6%, n=37), and photosensitivity (1.5%, n=33)

Withdrawals

  • 6.4% (n=145) discontinued treatment due to cheilitis, dyslipidaemia, deranged LFTs, mood changes, arthralgia/myalgia, and headache

 Complete remission and substantial improvement not defined; GAGS used at baseline but not at point of outcome measurement; data on long-term follow-up not available; retrospective study: incomplete documentation; missing data
Kim et al,48
2014		 20 Topical epidermal growth factor vs. vehicle cream Lesion count

  • IL count reduced by 33.5% (P<0.05) on rhGEF side; no significant reduction on control side

  • NIL count reduced by 25.2% (P<0.05) on rhGEF side vs. increased mean count on control side

Treatment success

  • Mean baseline IGA reduced from 2.9 to 1.85 on rhGEF side vs .no significant changes on control side (P<0.05)

 Local AEs

  • No significant AEs including skin irritation or allergic reactions

 Unclear process of randomization; small sample size; short duration of follow up
OTHER THERAPIES
Brownell et al,56
2021		 13 Topical bakuchiol (UP256) Lesion count

  • Mean % decrease in IL counts 26.9% (P=0.017) and 28.4% (P=0.013) at 8 weeks and 12 weeks, respectively

 Local AEs

  • Investigator-reported AEs included erythema, dryness, scaling, oiliness

Withdrawals

  • No participants discontinued due to AEs

 No control arm; no blinding; small sample size; short duration of follow-up
Isoda et al,73
2015		 18 Mild facial cleanser formulated w/ sodium laureth carboxylate and alkyl carboxylates (AEC/soap) Lesion count

  • 5 subjects had no acne lesions, 2 subjects had mild acne, and 11 had modest acne, compared to 7 patients with modest acne, 9 with mild acne, and 2 with moderate acne at baseline

  • Acne lesions were not detectable in 25% subjects

 Local AEs

  • No complaints of dryness or irritation

 20 patients recruited but only 18 analysed; self-reported as controlled trial, but no method of control identified; limitations of study not explored; inconsistent reporting of statistical significance

A/BPO: adapalene/benzoyl peroxide; AE: adverse event; ALA: aminolaevulinic acid; BPO: benzoyl peroxide; C/BPO: clindamycin/benzoyl peroxide; CDLQI: Children’s Dermatology Life Quality Index; CI: confidence interval; DL: diode laser; DLQI: Dermatology Life Quality Index; EGSS: Evaluator's Global Severity Score; Excellent or good therapeutic effect: >50% reduction in lesion count); FMR: fractional microneedle radiofrequency; FPS: Fitzpatrick skin type; GA: glycolic acid; GAGS: Global Acne Grading System; GAI: Global Assessment of Improvement; GIS: Global Improvement Score; ICG: idocyanine green; IGA: Investigator’s Global Assessment; IGA: Investigator's Global Assessment; IL: inflammatory lesion count; IPL: Intense pulsed light; ISGA: Investigator's Static Global Assessment; ITT: Intention To Treat; JS: Jessner’s solution; KAGS: Korean Acne Grading System; LED: light emitting diode; LFTs: liver function tests; MAL: Methyl aminolevulinate; NIL: non-inflammatory lesion count; NR: not reported; OR: odds ratio; PIH: post-inflammatory hyperpigmentation; QoL: Quality of Life; rhGEF: topical epidermal growth factor; SA: salicylic acid; SD: standard deviation; TLC: total lesion count