PDT in Medical and Aesthetic Dermatology: An European Perspective. Rolf-Markus Szeimies Recklinghausen, Germany

Transcription

1 PDT in Medical and Aesthetic Dermatology: An European Perspective Rolf-Markus Szeimies Recklinghausen, Germany

2 DISCLOSURE OF RELATIONSHIPS WITH INDUSTRY Rolf-Markus Szeimies, MD PhD F066 Photodynamic Therapy in Medical and Aesthetic Dermatology DISCLOSURES Almirall, Biofrontera, Galderma, LEO Pharma: Advisory Board Honoraria Almirall, Biofrontera, Galderma, Janssen Pharmaceuticals: Speaker Honoraria Biofrontera, Galderma, LEO Pharma, photonamic: Investigator Grants

3 FURTHER DISCLOSURE Rolf-Markus Szeimies, MD PhD F066 Photodynamic Therapy in Medical and Aesthetic Dermatology All drugs and procedures/combinations presented here in this talk are not approved in the U.S. by the FDA

4 Why is there pain with conventional PDT? Szeimies RM (2018) Pain perception during Photodynamic Therapy Why is Daylight PDT with MAL almost pain free? G Ital Dermatol Venereol 153: AK: application of MAL under occlusion Enrichment of protoporphyrin IX also in adjacent tissue during 3- hrs-incubation period Szeimies Upon illumination irritation of free nerve endings by reactive oxygen species (ROS) -> pain induction

5 56-yrs old patient with field cancerization Images from original publication 3 mo following MAL conventional PDT (with scalp block) Klein A. et al, BJD 2015

6 Daylight-PDT for Actinic Keratoses Wiegell S et al., Br J Dermatol 2008; 158: PDT for AK is painful, especially in field cancerized areas of face & scalp Better tolerability, when light at lower intensity is used for illumination? Comparison of conventional MAL-PDT (3 h incubation, LED 37 J/cm²) vs. daylight exposure (30 min MAL incubation followed by 2.5 h sun exposure) Image from internet

7 Less pain with MAL-daylight PDT Szeimies RM (2018) Pain perception during Photodynamic Therapy Why is Daylight PDT with MAL almost pain free? G Ital Dermatol Venereol 153: MAL-application, followed by daylight illumination for 120 min; Synthesis & continuous photoactivation of PPIX already within the mitochondria with the consequence of localized necrosis/apoptosis Consumption of PPIX by the photodynamic process ( photobleaching ) prevents from sensitization of adjacent nerves Szeimies

8 Noninferiority of DL-PDT to cpdt in AK Tomás-Velázquez A, Redondo P. De la terapia fotodinámica convencional a la terapia fotodinámica con luz de día en el tratamiento de las queratosis actínicas: revisión sistemática y metaanálisis. Actas Dermosifiliogr. 2017;108:

9 Natural Daylight PDT Recklinghausen Style Szeimies Chemical sunscreen SPF min before Lesion preparation (in case of crusty AKs) Application of photosensitizer thin layer no occlusion start of light exposure within 30 min light exposure outside for 2 h minimum LUX: 2,300; period between Apr-Oct (latitudedependent) minimum temperature: 10 C / 50 F

10 DL-PDT vs. cpdt in patients with face & scalp AK Sotiriou E, Evangelou G, Papadavid E et al. (2018) JEADV 32: pat., non-hyperkeratotic AK on face & scalp single tx, randomized split-face DL-PDT vs. c-pdt with MAL 3/12-month follow-up DL-PDT c-pdt Complete AK clearance at 3 months 77.9% 80.6% Complete AK clearance at 12 months 71.2% 73.7% Recurrence at 1 year 8.7% 8% Local adverse events more intense with cpdt Patients' preference was more for DL-PDT compared to cpdt

11 Long term efficacy of DL-PDT in AK with MAL Sotiriou E et al. J Eur Acad Dermatol Venereol Apr;32(4): Images from original publication

12 MAL vs. ALA-Nanoemulsion for DL-PDT of AK Räsänen JE et al. (2018) Br J Dermatol, Oct 17. doi: /bjd Prospective, randomized, double-blinded multicentre intraindividual comparison in 69 pat. with 767 symmetrical AKs (Olsen s type I-II) Single-session DL-PDT (randomized split-face design) Primary outcome clearance of AKs at 12 mo

13 MAL vs. ALA-Nanoemulsion for DL-PDT of AK Räsänen JE et al. (2018) Br J Dermatol, Oct 17. doi: /bjd After 12 mo, ALA cleared 299/375 AKs (79.7%), MAL 288/392 (73.5%) (p=.041); no difference in half-face analysis

14 MAL vs. ALA-Nanoemulsion for DL-PDT of AK Räsänen JE et al. (2018) Br J Dermatol, Oct 17. doi: /bjd After 12 mo, ALA cleared 299/375 AKs (79.7%), MAL 288/392 (73.5%) (p=.041); no difference in half-face analysis Image from original publication

15 MAL vs. ALA-Nanoemulsion for DL-PDT of AK Räsänen JE et al. (2018) Br J Dermatol, Oct 17. doi: /bjd After 12 mo, ALA cleared 299/375 AKs (79.7%), MAL 288/392 (73.5%) (p=.041); no difference in half-face analysis Painless with both PS, pain VAS 1.51 for ALA, 1.35 for MAL (p=.061) 26 pat. stronger skin reaction on ALA side, 7 on MAL side (p=.001) No difference in costs & cosmetical outcome

16 MAL vs. ALA-Nanoemulsion for cpdt of AK Serra-Guillén C et al. (2018) Br J Dermatol 179: Prospective, randomized, observer-blinded intraindividual comparison in 50 pat. with symmetrical AKs (Olsen s type I-II, > 8 per site) Median count of AK at scalp/face: 13.6 vs (MAL/ALA), 35 pat. with supraorbital/trochlear nerve block prior to PDT

17 MAL vs. ALA-Nanoemulsion for cpdt of AK Serra-Guillén C et al. (2018) Br J Dermatol 179: MAL more selective for AK lesions, ALA more unspecific fluorescence pattern and therefore more pronounced local skin reaction

18 MAL-PDT with light-emitting fabric (LEF) Vicentini C et al. (2018) Br J Dermatol, Oct 26. doi: /bjd Randomized, controlled phase II clinical study, non-inferiority design, intraindividual comparison in 25 pat. with symmetrical AKs (Olsen s type I-II, 154 vs. 156 lesions) Primary endpoint lesion complete response rate at 3 mo

19 MAL-PDT with light-emitting fabric (LEF) Vicentini C et al. (2018) Br J Dermatol, Oct 26. doi: /bjd Red laser light (635 nm), delivered through a flexible fabric during 1.5h with sequential emission at 12.3 mw/cm² for 1 min each (2 min dark time) which results in a total light dose of 37 J/cm² Images from original publication

20 MAL-PDT with light-emitting fabric (LEF) Vicentini C et al. (2018) Br J Dermatol, Oct 26. doi: /bjd At mo 3, LEF protocol with lesion complete response rate of 66.0% vs. 59.1% showed no inferiority compared to cpdt with red light LED Significant lower pain with LEF vs (p<.0001)

21 Calcipotriol-assisted MAL-PDT for AK Torezan L et al. (2018) Br J Dermatol 179: Randomized split-face trial w/wo pretreatment of calcipotriol ointment 50µg/g once daily for 15 d prior to c-pdt with MAL 20 pat. with scalp AKs. Overall clearance rates 92.1% for CAL-PDT and 82.0% for cpdt (p<.001)

22 Calcipotriol-assisted MAL-PDT for AK Torezan L et al. (2018) Br J Dermatol 179: Baseline day 5 post PDT day 90 post PDT CAL-PDT CAL-PDT CAL-PDT Images from original publication

23 Calcipotriol-assisted MAL-PDT for AK Torezan L et al. (2018) Br J Dermatol 179: Grade I AKs similar response rates, grade II AKs more improvement on CAL-PDT side (90% vs. 63%; p<.001) Before illumination, PPIX fluorescence higher on CAL- PDT side Pain, erythema, crusts & oedema more pronounced on CAL-PDT side

24 Case report Hailey-Hailey Disease & DL-PDT 58-yrs old female 20y history of recurrent erythematous, oozing and eczematous skin lesions in the intertriginous areas Positive family history for Hailey-Hailey disease Numerous therapies without success Daylight-PDT with MAL (single treatment) on right abdominal area

25 Case report Hailey-Hailey Disease & DL-PDT Szeimies Right abdominal area: pre-tx Right abdominal area: 6 mo post single course of DL-PDT, only hyperpigmentary changes, no exacerbation inbetween Left abdominal area: untreated with signs of Hailey-Hailey Disease

26 PDT for actinic cheilitis Author / year Drug (procedure conventional or daylight) Number of pat. Followup Result Chavez et al MAL (c) 16 3 mo 62.5% CCR Suarez-Perez et al MAL (c) 10 3 mo 80 % CCR Fai et al MAL (DL) mo 50% CCR Yazdani Abyaneh et al (systematic review) Choi et al ALA, MAL mo 62% CCR, 47% histological cure MAL (c+ Er:YAG pre-tx) mo 92% for PDT+laser vs. 59% for PDT alone at 3 mo RR 8% for combination and 50% for PDT alone at 12 mo

27 Case Report ALA-PDT for Actinic Cheilitis 59-years-old patient, since 1 year crust formation at lower lip Biopsy: Cheilitis actinica Application of ALA-containing patch (2 mg/cm²) for 4 hrs Illumination with red LED (37 J/cm²)

28 Case Report ALA-PDT for Actinic Cheilitis AC pre TX Patch application Patch removal after 4 hrs PPIX fluorescence with Woods light Szeimies

29 Case Report ALA-PDT for Actinic Cheilitis Application of cotton rolls Illumination with red light Hemorrhagic crust formation 5d after PDT CC after 50 days Szeimies

30 ALA-Patch-PDT for actinic cheilitis Radakovic S, Tanew A (2017) 5-aminolaevulinic acid patch-photodynamic therapy in the treatment of actinic cheilitis. Photodermatol Photoimmunol Photomed 33: Retrospective trial, 11 pat. with AC (15 lesions) 4h ALA-patch incubation, red LED light 37 J/cm² Follow-up for 3, 6, 9, 12 months CR after 3 mo 80% (12/15 lesions); recurrence in 2 lesions after 12 mo; complete clinical clearance rate 66.6% (10/15) Cosmetical results excellent, side effects all tolerable

31 DL-PDT for the treatment of actinic cheilitis Levi A, Hodak E, Enk CD et al. Photodermatol Photoimmunol Photomed (2018) in press 11 pat. with actinic cheilitis (3 w, 8 m), mean age 59.2 years Multiple treatment sessions with DL-PDT Cure rate 91% (10 of 11 pat.) Mean number of Tx to achieve clinical and histological remission: 2.7 Side effects: mild erythema and minimal to no pain during treatment

32 MAL-PDT vs. Imiquimod for AKs in OTRs Togsverd-Bo K et al. (2018) Br J Dermatol 178: Intraindividual study, field treatment of AK with MAL and IMIQ; 35 pat., 572 AKs (grade I-III) Similar areas on face, scalp, dorsal hands & forearms. One MAL and one IMIQ (3 weekly applications for 4 wks) session; repeat if incomplete Outcome measures: complete lesion response, skin reactions

33 MAL-PDT vs. Imiquimod for AKs in OTRs Togsverd-Bo K et al. (2018) Br J Dermatol 178: Majority of pat. (>70%) with 2 Tx. At mo 3, higher CR for MAL-PDT (median 78%) vs. IMIQ (median 61%) Fewer emergent AKs in PDT- vs. IMIQ-treated skin (0.7 vs. 1.5 AK, p=.04) Short term skin reactions higher for PDT, but faster resolution of skin reactions compared to IMIQ group (median 10 vs. 18 days, p<.01)

34 Summary Daylight-PDT with ALA & MAL serious alternative for Tx of AK Study results comparable with classical PDT and other Tx modalities Artificial light sources for c- and DL-PDT available MAL-PDT also of interest in OTR-patients with AK in respect of treatment and possible also prevention