Microneedle pretreatment can shorten PDT treatment time for actinic keratoses

Actinic keratosis treatment using microneedling followed by photodynamic therapy at a 20-minute aminolevulinic acid incubation time is considerably shorter, about as effective and less painful compared to conventional photodynamic therapy treatment, according to a recently published study in JAMA Dermatology.

Photodynamic therapy with one hour aminolevulinic acid incubation is a conventional approach in actinic keratoses field therapy. Other commonly used treatments include topical 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, chemical peels and ablative laser resurfacing. But long-term outcomes from available field therapy options vary greatly. And when it comes to photodynamic therapy treatment for these patients, pain is the most severe adverse effect. It can lead to patients’ stopping or interrupting treatment, or refusing to have such treatments in the future, according to the study.

“The development of new or improved treatment modalities for [actinic keratoses] thus mandates considerations in addition to efficacy, such as duration, convenience and patient adherence to treatment,” the authors write.

THE DESIGN

In this randomized clinical trial, researchers report on 32 actinic keratoses patients, each with at least three distinct grade II facial actinic keratoses. Patients were randomized to pretreatment with either a 200 um microneedle roller or sham roller. Then, they were randomized to photodynamic therapy with either a 20-minute or 10-minute incubation time. Post-incubation, patients were exposed to blue light, for 1,000 seconds or a total 10 J/cm² fluence. The authors report on outcomes four weeks posttreatment.

COMPARING TREATMENTS

Microneedle-assisted photodynamic therapy with a 20-minute aminolevulinic acid incubation resulted in a 76 percent clearance of actinic keratoses, versus 58 percent on the sham side. Three patients achieved complete clearance compared to zero in the sham side, but that wasn’t a statistically significant finding.

The improved actinic keratoses counts with this treatment were superior to sham and similar to the 78.6 percent reported outcome with traditional photodynamic therapy treatment with one hour aminolevulinic acid incubation.

Transepidermal water loss increased by an average 36 percent on the microneedle side of the 20-minute incubation treatment, versus 0 percent on the sham side. And pain on the microneedle pre-treated side was an average 1.3 on the 10-point visual analog scale, compared to 0.3 on the sham side. Pain during blue light exposure was not significantly different between the microneedle and sham sides.

In the 10-minute incubation group, average actinic keratoses clearance was 43 percent on the microneedle pretreated side compared to 38 percent with sham, but that wasn’t a significant difference, according to the authors.

Transepidermal water loss increased an average of 40 percent for the microneedle side, compared to 2 percent on the sham side. And while pain was greater in the microneedle pretreated side, at an average 1.4 on the visual analog scale, versus 0.3 on the sham side, pain during blue light exposure was not significantly different between the sides.

While pain levels for the microneedle groups were higher than for sham sides, pain with the shorter therapies is still less than with the conventional approach. In research looking at photodynamic therapy with aminolevulinic acid incubation times of one to three hours, 60 percent of patients reported moderate to severe pain. None of the patients in this study reported moderate to severe pain, the authors note.

They suggest the 10-minute incubation time might have fallen short in efficacy because while the microneedling might have expedited aminolevulinic acid’s delivery through the stratum corneum and epidermis, the following steps for eventual apoptosis likely require more time.

THE FUTURE

The study is limited because of its size and short durations, the authors write. Future studies should look at actinic keratoses clearance over a longer time period; look more at the microneedle-assisted 20-minute incubation photodynamic therapy approach; and analyze the therapy’s effect on areas other than the face.

“Overall, the findings are promising for shortening treatment time and achieving greater patient satisfaction for [photodynamic therapy] without compromising efficacy,” they write.

Disclosures

The study was supported in part by the UC Davis Medical Student Research Fellowship to study author Lauren A. Hassoun, B.S., MAS.

References

Petukhova TA, Hassoun LA, Foolad N, et al. “Effect of Expedited Microneedle-Assisted Photodynamic Therapy for Field Treatment of Actinic Keratoses: A Randomized Clinical Trial.” JAMA Dermatology. July 2017. DOI: 10.1001/jamadermatol.2017.0849.