Efficacy and safety of single microneedle radiofrequency vs. photodynamic therapy on moderate-to-severe acne vulgaris: A prospective, randomized, controlled study

To the Editor: Acne vulgaris is a prevalent skin disorder affecting both physical and psychosocial health.[1] Although photodynamic therapy (PDT) exists for moderate-to-severe acne, due to its adverse reactions, we are still looking forward to a novel therapeutic option with fewer side effects. Recently, radiofrequency has been used to treat moderate acne.[2] In this study, we aimed to evaluate the efficacy and safety of moderate-to-severe acne treatment based on a single microneedle with radiofrequency (MRF) vs. PDT during three consecutive sessions through a prospective, randomized, and controlled trial study. This study was approved by the Institutional Review Board and the Ethics Committee of Xiangya Hospital of Central South University (No. 201911298) and was catalogued in the Chinese Clinical Trial Registry (ChiCTR1900028625). Written informed consent was obtained from all patients. The sample size calculation was performed with at least 80% power and a significance level of 0.05. To detect the smallest clinically important mean difference of 30% between both groups, at least 36 patients in each group were needed. To compensate for possible withdrawal, 80 patients with Fitzpatrick skin types III to IV and moderate-to-severe acne as defined by the Investigator Global Assessment (IGA) scale of 3 or 4 were enrolled. The exclusion criteria were the following: history of photosensitive disorders; use of medications, such as oral isotretinoin for 6 months or more and oral contraceptives or antibiotics for 4 weeks or more; history of facial procedures for 4 weeks or more, and pregnancy or lactation in female subjects. All patients were prohibited from using any anti-acne treatment, except for standard washing and moisturizing procedures, while participating in the study. We used random number table formed by SPSS version 19.0 (SPSS, Chicago, IL, USA) to allocate participants to the PDT or MRF group. The allocation to treatment was concealed in an opaque envelope and revealed to the clinician on the day of first treatment. In the MRF group, patients adopted a supine position, and an antenna endplate was positioned beneath patient’s nape to set a monopolar circuit. A 3.5-mm-long needle was inserted into the lesional follicular pore at an angle of 60–70° [Supplementary Figure 1, https://links.lww.com/CM9/B790]. Using an electrosurgical apparatus (UnicornⅠ, Shenzhen Peninsula Medical Inc, China), a high-frequency current was then applied 1–2 times per lesion for 0.25–0.60 s at an intensity of approximately 6–8 W. The average treatment duration was about 45 min. In the PDT group, 5% aminolaevulinic acid (ALA) solution (Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd., Shanghai, China) was applied evenly to the face, and the application site was covered with an occlusive, non-absorbent dressing for 90 min. The lesions were irradiated with 100 mW/cm2, 90 J/cm2, red LED light (633 nm) (Wuhan Yage Optic and Electronic Technique Co. Ltd., Wuhan, China) for 15 min. Treatments were performed as three consecutive sessions at 2-week intervals, with a follow-up visit 12 weeks after the final treatment. The participants received treatment from the same operator. Two dermatologists who were blind to treatment allocation and not affiliated with patient treatment performed clinical evaluations based on photographs before each treatment and 4 weeks and 12 weeks after the final treatment. Objective acne severity assessments were performed using individual acne lesion counts and the IGA score. We defined treatment success as an improvement of at least two grades (mild, almost clear, or clear) of the IGA score from baseline. Patients’ subjective assessments of satisfaction were surveyed with a 10-point scale (0: no improvement; 10: excellent improvement). Patient-reported outcomes can be considered secondary measures (pain and side effects). Pain sensation during treatments was reported using a visual analog scale (VAS), ranging from 0 to 10 (0: no pain; 10: extreme pain). Statistical analysis was performed using SPSS. Chi-square (χ2) test and Fisher’s exact test were used for the comparison of categorical data. The independent samples t-test and Mann–Whitney U test were used to analyze quantitative data, and the repeated-measures ANOVA test was used to analyze repetitive measurements. Data were expressed as “mean (standard deviation [SD]),” and percent (%) where appropriate. A P-value <0.05 was considered statistically significant. The demoimagedata characteristics of subjects in the MRF and PDT groups are shown in Supplementary Table 1, https://links.lww.com/CM9/B790. All patients exhibited significant reduction of both inflammatory and non-inflammatory lesions after three treatments. For inflammatory lesions, MRF led to a greater mean percentage reduction in lesion counts from baseline vs. PDT after the third session (81% vs. 73%). A significant reduction in inflammatory lesions was observed after as early as the first session in the MRF group and persisted until the end of the study. Because of reactive acne, some of the subjects in the PDT group experienced an increase in inflammatory lesions after the first session [Supplementary Figure 2A, https://links.lww.com/CM9/B790]. MRF also resulted in a significant reduction in non-inflammatory lesions after the second session (55% vs. 44%), but there was no significant difference in lesion improvement between the two regimens after the 3rd session and the final follow-up visit [Supplementary Figure 2B, https://links.lww.com/CM9/B790]. Clinical photographs that illustrate the typical improvement are presented in Figure 1. Subjects in the MRF group displayed greater improvement, and no pustular eruptions were observed during treatment sessions. Similar results were observed for the IGA success rate. Significantly, more subjects in the MRF group were IGA clear/almost clear than those in the PDT group at the 2nd and 3rd treatment sessions; the difference in IGA success rate was highest at the 3rd session (25% superior for PDT) [Supplementary Figure 3A, https://links.lww.com/CM9/B790]. The subject’s self-assessment for the degree of acne improvement generally paralleled the physician’s evaluation [Supplementary Figure 3B, https://links.lww.com/CM9/B790]. The MRF treatment tended to be awarded higher satisfaction scores than the PDT treatment during three treatment sessions.Figure 1: Clinical improvements were observed in both groups. Photographs of the MRF group (A) and the PDT group (B) at BL, PT1, 2, 3 and the final F/U. BL: Baseline; F/U: Follow-up; MRF: Single Microneedle Radiofrequency therapy; PDT: Photodynamic therapy; PT: Post-treatment.About adverse events, the mean pain score, erythema, edema, scaling and dryness, and scar formation throughout the treatment sessions in the MRF group were significantly lower than those in the PDT group. The incidence of post-inflammatory hyperpigmentation (PIH) was 42.5% in the PDT group while 10% in the MRF group. PIH faded completely after 3–6 months without any medical treatment, except shielding from sunlight. Transient acneiform eruption was observed in 32.5% in the PDT group and none from the MRF group. No uncontrollable reactions occurred; so, no oral hormones or antibiotics were taken. Overall, the MRF group showed fewer adverse events. Detailed safety profile information is presented in Supplementary Table 2, https://links.lww.com/CM9/B790. Clinical and histopathological studies have proven that MRF can destroy sebaceous glands, reduce the levels of inflammatory mediators, through RF thermal damage, and physically disrupt hyperkeratotic plugs in the follicular infundibula by the microneedle.[3] In the present study, we observed that MRF induced a faster response and a more mild complication profile as compared with PDT, although the overall degree of improvement at the end was similar. The significant reduction in inflammatory lesions was observed after the first session, and sterile pustular eruptions were not observed after the MRF treatment, which greatly increased the subjects’ satisfaction and improved patients’ compliance with follow-up treatments. Besides, the PDT group experienced more pain, which is consistent with the previously reported clinical experience while MRF was accompanied by few adverse events. This might be attributed to the local motorized needle insertion and motion which minimizes trauma to the epidermis in MRF. The severity and course of the pigmented lesions were more remarkable in the PDT group which may be caused by the higher accumulation of PpIX in not only the inflammatory acne lesions but also in the surrounding normal skin.[4] While patients may have less concerns about the hyperpigmentation caused by MRF, the needle delivers electrical current to the dermal structures at the desired depth with less epidermal damage.[5] Moreover, MRF does not require that patients avoid sun exposure for 48 h after treatment and can be used in patients with photosensitivity. The MRF therapy appears more effective at improving acne scars at the later stages of treatment. In fact, various studies have demonstrated the efficacy of RF devices for skin texture improvement, acne scarring reduction, and pore size reduction via inducing profound neoelastogenesis and neocollagenesis.[6] Considering the “minimal scars” exactly affect patients’ quality of life, it is noteworthy that no subjects in the MRF group experienced acneiform lesion eruptions. Concurrent improvement of acne and scaring through dermal remodeling could be additional clinical advantages of MRF. In conclusion, this trial demonstrates the efficacy and safety of the MRF and PDT approaches in the treatment of moderate-to-severe acne. Participants from both groups achieved similar clinical improvement, but MRF showed more rapid efficacy and a better safety profile. Therefore, MRF, as a monotherapy or as a component of combination therapy, would be a viable alternative to PDT to treat moderate-to-severe acne. Conflicts of interest None. Funding This work was supported by grants from the National Natural Science Foundation of China (Nos. 81573074 and 81874246).