No Link Between PCSK9 Inhibitors and Vitiligo Risk: Study

New research published in the Journal of Investigative Dermatology shows no evidence linking PCSK9 inhibitors to an increased risk of vitiligo.

Researchers exploring whether inhibiting PCSK9 influences the development of vitiligo conducted a Mendelian randomization study of large genome-wide association studies and identified genetic variants associated with PCSK9 expression. The data were drawn from two large European public health databases (UK Biobank and deCODE).

According to the results, lipid-lowering Mendelian randomization indicated PCSK9 may have a role in reducing vitiligo risk (OR = 0.71 [95% CI], 0.52 to 0.95); which was replicated in PCSK9-inhibition Mendelian randomization analyses across 2 separate databases (UK Biobank: OR = 0.82 [95% CI], 0.71 to 0.96; deCODE: OR = 0.78 [95% CI], 0.67 to 0.91].

"Remarkably, our results indicated that only the PCSK9 inhibition (targeted by alirocumab and evolocumab) demonstrated a significantly reduced risk of vitiligo," the authors wrote in their study. "We identified CXCL12, CCN5, FCRN1, LGMN, and FGF2 as proteins mediating the association between PCSK9 and vitiligo, whereas more well-known, lipid-related biomarkers such as LDL-C did not seem to act as mediators."

The researchers emphasized the importance of Mendelian randomization in clarifying drug safety profiles, nothing that the study methodology strengthens confidence in the safety of PCSK9 inhibitors, particularly for dermatological outcomes. They reported that the study findings are in line with previous safety data on PCSK9 inhibitors in patients requiring intensive lipid-lowering therapy.

"This research provides clarity and supports the continued use of PCSK9 inhibitors without concerns about an elevated risk of vitiligo," the authors concluded.

Source: Kang TJ, et al. Journal of Investigative Dermatology. 2025 Doi:10.1016/j.jid.2024.07.021