Table 1.

Characteristics of studies and main outcomes.

+First Author/Year of publication	Type of study	Intervention	Number of patients	Time of assessement	Complete Clearance in %(Unless indicated otherwise)
Dirschka et al, 2013	Two prospective randomized controlledphase III trials	MAL-PDT versus BF-200 ALA	482	6 and 12 months	MAL-PDT: 36% and BF-200 ALA: 47%
Serra-Guillén et al, 2018	Randomized intraindividual comparative	MAL-PDT versus BF-200 ALA	25	1 month	MAL-PDT: 56% and BF-200 ALA: 62%
Neittaanmäki Perttu et al, 2014	Randomized double-blinded non-sponsored prospective	MAL-PDT versus BF-200 ALA	13	3 months	MALPDT: 74.2% and BF-200 ALA: 84.5%
Dirschka et al, 2018	Randomized intra-individual non-inferiorityphase III	DL-MAL-PDT versus BF-200 ALA DL-PDT	52	12 weeks	BF-200 ALA DL-PDT: 79.8% and MAL-DL-PDT: 76.5%
Reinhold et al, 2016	Randomized, double-blind, phase III, multicentre	BF-200 ALA combined with the BF-RhodoLED versus placebo	55 patients received BF-200 ALA, 32 received placebo	3 months with a potential of an additional PDT session	BF-200 ALA: 91% and placebo: 22%
Räsänen et al, 2019	Non-sponsored, prospective randomized double-blind multicentre	BF-200 ALA versus MAL in DL-PDT	69	12 months	BF-200 ALA DL-PDT: 79.7% and MAL DL-PDT: 73.5%
Moloney et al, 2007	Randomized, double-blind, prospective	MAL-PDT versus ALA-PDT	15	1 month	Mean reduction from baseline in AK counts with ALA-PDT: 6.2 +/− 1.9 and MAL-PDT: 5.6 +/− 3.2
Apalla et al, 2010	Randomized placebo-controlled	ALA-PDT versus placebo	39	12 months	ALA-PDT: 64% and placebo: 26%
Kleinpenning et al, 2010	Comparative to baseline	MAL-PDT	14	3 months	42.9%
Arisi et al, 2020	Randomized, cohort	MAL-PDT, ingenol mebutate gel and diclofenac plus hyaluronate gel	90 patients, 30 in each cohort	90 days	MAL-PDT: 23.07%, ingenol mebutate: 30% and diclofenac plus hyaluronate: 14.28%
Sotiriou et al, 2015	Randomized intraindividual comparison	MAL-PDT versus. Imiquimod 5%	44	12 months	No statistically significant difference between the two mirrored fields regarding the development of new lesions.
Jansen et al, 2019	Randomized, multicenter	5% fluorouracil, 5% imiquimod, MAL-PDT, or 0.015% ingenol mebutate	624	12 months	Fluorouracil: 74.7%, imiquimod:53.9%; MAL-PDT: 37.7% and ingenol mebutate: 28.9%
Karrer et al, 2019	Open, interventional, multicenter	MAL DL-PDT	50	3 months	62%
Assikar et al, 2020	Controlled randomized intra-individual	DL-PDT versus PDT	26	3 and 6 months	3 months: DL-PDT: 90.5% and PDT: 94.2%; 6 months: DL-PDT:90.0% and PDT: 94.6%
Sotiriou et al, 2017	Randomized intra-individual comparative	DL-PDT versus PDT	23	12 months	DL-PDT: 78% and PDT: 80.6%
Lacour et al, 2005	Randomised investigator-blinded controlled phase III	DL-PDT and PDT	108	12 weeks	DL-PDT: 74% and PDT: 70%
Genovese et al, 2016	Intraindividual comparative	DL-PDT versus ingenol mebutate	27	3 months	DL-PDT: 72.4% and ingenol mebutate: 73.6%
Wiegell et al, 2012	Randomized multicenter	MAL DL-PDT	145	3 months	Grade I AKs: 75.9%, grade II: 61.2% and grade III: 49.1%
Ulrich et al, 2021	Vehicle-controlled phase III	BF-200 ALA-PDT versus vehicle	50	12 months	BF-200 ALA-PDT: 86.0% and vehicle: 32.9%
Salido-Vallejo et al, 2020	Single-centre, intraindividual, retrospective	BF-200 ALA-PDT and DL-PDT(combPDT) versus DL-PDT	19	12 weeks	combPDT: 31.6% and DL-PDT: 15.8%
Gracia-Cazaña et al, 2019	Observational, prospective, comparative	DL-PDT versus DL-PDT plus ingenol mebutate	43	12 months	DL-PDT: 75.2% and DL-PDT plus ingenol mebutate: 54.6%
Petukhova et al, 2017	Randomized, single-blinded, split-face controlled, 2-arm clinical trial.	10- or 20-minute ALA incubation times, after pretreatment with a microneedle or sham roller	32	1 month	20-minute incubation arm: microneedle: 76% and sham roller: 58%; 10-minute incubation arm: microneedle: 43% and sham roller: 38%
Torezan et al, 2013	Pilot split-face comparative	Microneedling-PDT versus MAL-PDT	10	1 and 3 months	At day 90, facial erythema (p = .04) and coarse wrinkles (p = .002) improved on the microneedling-PDT side, compared to MAL-PDT (p = .01).
Torezan et al, 2018	Randomized split-scalp comparative	Calcipotriol-MAL-PDT versus. MAL-PDT	20	3 months	Calcipotriol-MAL-PDT: 92.1% and MAL-PDT: 82.0%
Bullock et al, 2022	Interventional cohort-controlled	Oral vitamin D3 combined with PDT versus MAL-PDT	29 patients in each group	3 to 6 months	Oral vitamin D3 combined with PDT: 72.5% and MAL-PDT: 54.4%
Maytin et al, 2018	Bilaterally controlled	PDT plus topical 5-fluorouracil versus PDT	17	3, 6, 9, and 12 months	PDT plus topical 5-fluorouracil: 75% and PDT: 45% at 3 months; PDT plus topical 5-fluorouracil: 67% and PDT: 39% at 6 months
Pires et al, 2019	Intra-individual comparative	Acoustic pressure wave ultrasound-CO2-MAL-PDT versus MAL-PDT	15	6 months	Acoustic pressure wave ultrasound-CO2-MAL-PDT: 72% and MAL-PDT: 65%
Vrani et al, 2019	Randomized intraindividual comparison	Fractional CO2 laser-PDT versus PDT	42	12 months	Fractional laser-PDT: 47.2% and PDT: 52.3%
Togsverd-Bo et al, 2012	Randomized comparative	Fractional CO2 laser-PDT versus PDT	15	3 months	Fractional laser-PDT: 88% and PDT: 59%
Bento et al, 2021	Randomized controlled four-arm comparative	DL-PDT; DL-PDT + microneedles; DL-PDT + CO2 laser; DL-PDT +microdermabrasion	40 patients, 10 patients at each group	3 and 6 months	The DL-PDT+ microneedles group had a higher AK-clearance after 1 (p=0,002) and 3 (p=0,034) months. Similar in every group at 6 months (p=0,441)
Togsverd-Bo et al, 2015	Randomized controlled	Ablative fractional laser (AFL)-assisted DL-PDT) (AFL-dPDT) versus DL-PDT), PDT and AFL alone (AFL)	16	3 months	AFL-dPDT: 74%, DL-PDT: 46%, PDT: 50% and AFL: 5%
Togsverd-Bo et al, 2015	Randomized intra-individual controlled	Repeated PDT every 6 months for AK prevention	25	3 years	New AKs in 63% of patients in untreated skin areas versus 28% of patients in PDT-treated skin
Piacquadio et al, 2020	Randomized, parallel-group, evaluator-blinded	ALA 2× versus ALA 3× versus vehicle PDT	166	52 weeks	ALA 2x: 36.0%, ALA 3x: 37.5%, vehicle: 18.9%

ALA = 5-aminolevulinic acid; BF200-ALA = Nanoscale-lipid vesicle formulation with the prodrug 5-aminolevulinic acid;

PDT = photodynamic therapy;

AFXL-PDT = ablative fractional laser resurfacing photodynamic therapy;

DL = daylight photodynamic therapy;

MAL-PDT = methyl aminolevulinate photodynamic therapy.