Combining Microneedling and Tranexamic Acid for Melasma: Efficacy and Satisfaction

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Melasma, a condition that affects 1% to 50% of the population, is often treated using topical applications, oral medications, and procedural interventions.¹ Despite a generally positive response to established treatments, a complete resolution of melasma is rare, with the condition often recuring. Because of this, ongoing research into more session-efficient and cost-effective alternatives, as well as personalized treatments, is necessary.² A recent study aimed to investigate the efficacy, safety, durability, and overall satisfaction of combining microneedling with tranexamic acid (TA) in treating melasma, as both have attracted attention in recent years for their effectiveness.³

Study Design

This randomized clinical trial assessed the use and long-term satisfaction of microneedling assisted drug delivery of different concentrations of TA in combination with topical modified Kligman formula (consisting of 4% hydroquinone, 3% vitamin C and 3% retinol by volume, incorporated into a cold cream base) compared to the topical treatment alone, in treatment of melasma.

Patients were randomly assigned to groups A or B, 50 patients in each. Patients in group A were instructed to use a topical modified Kligman formula regularly on 1 side of the face on even nights, and on the opposite side, 3 sessions of microneedling along with 10% topical TA at 1-month intervals. Patients in group B used the topical modified Kligman formula on both sides of the face in the same manner as group A, but were also assigned 3 sessions of microneedling along with 4% TA were performed at 1-month intervals, and on the opposite side, 3 sessions of microneedling along with 10% TA were performed at 1-month intervals.

This gave researchers 4 treatment groups defined as:

• Group A1: only the topical modified Kligman formula
• Group A2: only three sessions of microneedling with topical 10% TA at 1-month intervals
• Group B1: topical modified Kligman formula + 3 sessions of microneedling with topical 4% TA at 1-month intervals
• Group B2: topical modified Kligman formula + 3 sessions of microneedling with topical 10% TA at 1-month intervals

Evaluation and Follow-ups

For each patient, baseline information was recorded and severity of melasma was evaluated using the Modified Melasma Area and Severity Index (mMASI) and the visual analogue scale (VAS) at baseline, 1 month, and 2 months during treatment, and subsequently 1 and 4 months after the final session. Relative to baseline, researchers identified these as 0,1-,2-,3-, and 6-month check ins.

During each treatment session, researchers noted patients were monitored for adverse events including post-inflammatory hyperpigmentation (PIH), and their treatment tolerability. The study stated that patient satisfaction was evaluated using a quartile measure: poor (0%–24%), moderate (25%–49%), good (50%–74%), and excellent (75%–100%).

Efficacy: mMASI Score

Researchers found that groups B1 and B2 did not show significantly different reductions compared to group A1 during treatment. However, group A2 was significantly less effective than A1 (mean difference (MD): −39%, (−50%, −29%)). Differences between B1 and B2 were not found to be significant in most comparisons.

The study stated that standardized mean differences (SMD) indicated that A1 had a “substantial” effect in reducing hemi-mMASI scores, while B1 and B2 showed moderate and small effects compared to A1, respectively. Post-treatment, researchers found impacts diminished across all groups, with A1 remaining significantly more effective than A2. When comparing B1 to B2, the study stated the difference in reducing hemi-mMASI scores was moderate and not statistically significant (SMD: 0.3 (−0.25, 0.86)).

In patients without PIH, researchers observed a large but not significant effect in B1 compared to A1 during treatment (SMD: 0.96 (0.37, 1.55)). B2 was found to exhibit a considerably large effect relative to A1 (SMD: 1.95 (1.28, 2.63)). Post-treatment, both B1 and B2 continued to demonstrate greater effectiveness than A1, with researchers finding B2 significantly more effective than B1.

Efficacy: VAS Score

The study found that A1 significantly reduced VAS scores more than A2. Researchers stated that B1 showed a minor VAS score reduction in the first month but improved substantially by the second month. B2 had a moderate effect compared to A1, but the study stated the difference between B2 and B1 was minor and not statistically significant.

In patients without PIH, the study stated B2 demonstrated a large and significant effect compared to A1. The effectiveness of B2 compared to B1 was initially large but researchers found it diminished after treatment stopped.

Tolerability and Adverse Events

Overall, researchers stated that PIH was reported in 11 patients (22%). PIH was more frequent in A2, affecting 28% of hemi-faces. Researchers found that PIH occurrence was equal in combination treatment groups B1 and B2, each reporting 16% incidence. No cases of PIH were observed in group A1.

PIH was found to be strongly associated with Fitzpatrick skin phototype. Specifically, researchers stated only 25.89% of patients with skin phototype III experienced PIH, while 73.3% of those with phototype IV experienced it as well. For skin phototype III, the study stated the type of treatment did not significantly affect PIH rates. However, for phototype IV, researchers found the type of treatment significantly influenced PIH, with bilateral cases more common in group B and unilateral cases more common in group A, especially A2 (p = 0.018). Four individuals in group B, using both 4% and 10% TA-microneedling with topical therapy, had a high incidence of PIH.

The study stated that no eczema or skin dryness was reported in any treatment group, and treatments were well-tolerated across all 4 treatment groups.

Patient Satisfaction

Researchers stated patient satisfaction was highest in treatment groups B1 and B2, with 72% of participants in these groups reporting excellent satisfaction. In contrast, the control group A1, which received only the modified Kligman formula, had 8% of participants reporting excellent satisfaction, while 84% reported good satisfaction. Group A2, which used microneedling with 10% TA, had the lowest satisfaction, with 72% reporting only moderate satisfaction.

Regarding treatment durability, defined as at least a 30% reduction in mMASI score at six months, researchers found there was a significant association with the type of treatment (p < 0.0001). Group A2 had the lowest reported durability rate at 16%, while group B2 had the highest at 72%.

Conclusion

The study stated that all treatments in the trial effectively reduced melasma severity, though improvements lessened after treatment ended. The modified Kligman formula was found to be more effective than microneedling with 4% TA. However, when microneedling with 4% or 10% TA was combined with the modified Kligman formula, and when patient selection prioritized those at lower risk for PIH (like those with lighter skin tones), researchers stated this combination showed superior benefits compared to the standard topical treatment. No significant difference was observed between the 2 TA concentrations in these combinations.

The study noted that although there are times when this method should be employed, it is not a catch-all treatment. “In patients assessed at high risk for PIH, such as those with darker skin phototypes, during warmer seasons, or in patients who appear to have poor compliance with adequate sun protection, it is advised to avoid microneedling due to its high risk for PIH. Instead, alternative methods of TA application, such as topical tranexamic acid or microinjection, should be considered,” the study stated.

For future research, the study suggested further studies are needed to evaluate the efficacy and safety of this modified Kligman Formula for melasma treatment, particularly to assess its potential in reducing adverse events.

References

1. Ogbechie-Godec OA, Elbuluk N. Melasma: an Up-to-Date Comprehensive Review. Dermatol Ther (Heidelb). 2017;7(3):305-318. doi:10.1007/s13555-017-0194-1
2. Sunder S. Relevant Topical Skin Care Products for Prevention and Treatment of Aging Skin. Facial Plast Surg Clin North Am. 2019;27(3):413-418. doi:10.1016/j.fsc.2019.04.007
3. Aghdam SB, Mohammad AP, Hosseini-Baharanchi FS, et al. Efficacy, safety, tolerability and treatment durability of microneedling plus topical tranexamic acid in combination with topical modified Kligman lightening formula for melasma: A four-arm assessor and analyst blinded randomized controlled clinical trial. J Cosmet Dermatol. 2024; 00: 1-13. doi:10.1111/jocd.16464