Prostaglandin Analogues, Phosphodiesterase Inhibitors Effective in Vitiligo as Monotherapy or Add-On Modalities

Monotherapy or combination therapy involving prostaglandin analogues (PGAs) and phosphodiesterase inhibitors (PDEIs) are effective in patients with vitiligo, according to a review published in the Journal of Cosmetic Dermatology.¹

According to researchers, both types of therapies outperform traditional therapies such as topicals or phototherapy modalities.

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Background and Methods

A 2009 study published in the British Journal of Dermatology reported a high portion of patients with vitiligo achieving marked response with PGAs. One hundred percent of segmental vitiligo lesions, 63% of focal patches, and all scalp, neck, and trunk lesions demonstrated moderate to excellent response.² PDEIs such as apremilast, for example, have also demonstrated promise.³

In order to assess the capabilities of both treatment classes as monotherapies or in combination with other therapies, researchers conducted a systematic review involving an extensive search across several databases including studies up to May 2023.

Inclusion criteria covered studies on both adult and pediatric patients with segmental and non-segmental vitiligo. Studies involving in vitro or animal research, or focusing on therapies outside of PGAs and PDEIs, were excluded from review. Two independent reviewers screened the titles and abstracts, followed by full-text evaluations and data extraction, with discrepancies resolved by a third expert.

Findings

From an initial pool of 532 records retrieved from multiple databases, researchers filtered the data to focus on relevant research. After removing duplicates and screening records by title and abstract, 78 articles were selected for full-text review. Ultimately, 42 studies met the criteria for data extraction.

The study reviewed 14 case reports involving 54 individual cases of vitiligo. The average age of patients was 22.7 years, with a notable female predominance (70.8%). The majority of lesions were located on the face (83%), with fewer on limbs and trunk. Most lesions were patches (75%), and the majority of cases (82%) were progressive.

Researchers evaluated both the PGA and PDEI treatment classes, reporting PGAs such as bimatoprost, latanoprost, and travoprost exhibiting variable outcomes with adverse effects like localized hypertrichosis and erythema reported. Among PDEIs, apremilast was predominantly used, with mixed results regarding efficacy and adverse effects such as headache and gastrointestinal discomfort. Crisaborole, another PDEI, demonstrated better outcomes but posed issues, such as the worsening of acne in some cases..

The study also included 25 analytical and comparative studies, focusing on a larger patient cohort and exploring the comparative effectiveness of various treatments. The average age was 27.6 years, with a nearly equal distribution between progressive and non-progressive vitiligo cases.

Latanoprost was shown to be effective when compared to placebo and combined with narrowband UVB (NB-UVB) therapy. Combination therapies involving latanoprost, NB-UVB, and microneedling resulted in improved repigmentation, particularly for facial and trunk lesions.

Bimatoprost was comparatively effective to topical tacrolimus, and when combined with NB-UVB or fractional CO2 laser, it enhanced treatment outcomes. Dinoprostone and non-specified PGE2 treatments demonstrated comparable efficacy to other therapies but with variable adverse effect profiles.

Travoprost was effective when combined with black pepper extracts, though adverse effects like erythema were noted. Apremilast demonstrated mixed results when compared to other treatments like oral methylprednisolone and photochemotherapy, and a combination of apremilast with NB-UVB showed promising results in some studies but was inconsistent across the board.

Conclusions

The review may have been limited by small sample sizes and differences in study settings or treatment combinations. To address these limitations and explore the utility of PGAs and PDEIs further, researchers recommended larger-scale, randomized clinical trials comparing PGAs and PDEIs with placebo before comparing it in the context of combination therapies.

"PGAs and PDEIs appear to induce satisfactory to near total repigmentation in patients with vitiligo. Side effect profiles are mild and tolerable and results are significant for stable and unstable vitiligo, in both adult and pediatric patients," according to Pourriyahi et al. "We conclude that PGAs and PDEIs, either as a monotherapy or an add-on, can be considered effective treatments for vitiligo and promising last resorts for those resistant to multiple other therapies."

References

1. Pourriyahi H, Hosseini NS, Nooshabadi MP, et al. Utility of prostaglandin analogues and phosphodiesterase inhibitors as promising last resorts for the treatment of vitiligo: a systematic review, from mechanisms of action to mono-, combination and comparative therapies. J Cosmet Dermatol. August 19, 2024. https://doi.org/10.1111/jocd.16468
2. Kapoor R, Phiske MM, Jerajani HR. Evaluation of safety and efficacy of topical prostaglandin E2 in treatment of vitiligo. Br J Dermatol. 2009; 160: 861-863.
3. Huff SB, Gottwald LD. Repigmentation of tenacious vitiligo on apremilast. Case Rep Dermatol Med. 2017; 2017:2386234.