Valproic acid may be protective against melanoma

Exposure to valproic acid seems to reduce the risk of melanoma, a recent study has found. That this may be due to residual confounding cannot be ruled out, however.

Researchers conducted a retrospective cohort study of 2,213,845 adults, of whom 22,355 had a history of exposure to valproic acid. The incidence rate of melanoma was significantly higher in the unexposed vs exposed participants (92.6 vs 64.0 cases per 100,000 person-years; p<0.001). Incidence was observed over a mean follow-up of 6.9±5.4 years.

Unadjusted Cox proportional hazards regression analysis found a 36-percent decrease in the risk of melanoma among valproic acid-exposed participants (hazard ratio [HR], 0.64, 95 percent confidence interval [CI], 0.51–0.79). Adjusting for covariates such as age, sex, and ambulatory healthcare use slightly attenuated the magnitude of the effect but not its significance (HR, 0.72, 95 percent CI, 0.58–0.90).

There were also slight differences between exposed and unexposed participants in terms of tumour characteristics upon presentation. Those exposed to VPA, for instance, did not show thick tumours, and were more likely to have local malignancies, though statistical significance over their exposed comparators was not achieved. Tumour behaviour did not differ between exposure subgroups.

The researchers then looked at the number of filled valproic acid prescriptions as a time-varying factor as a surrogate for exposure duration. They found that filling 1–3 prescriptions almost halved the risk of melanoma (HR, 0.48, 95 percent CI, 0.29–0.79), but at greater cumulative durations, no such effect was observed (≥12 fills: HR, 0.82, 95 percent CI, 0.59–1.16).

“[L]ack of a dose-effect necessitates interpreting these results with caution. Future studies validating our findings using additional large administrative databases will help to better elucidate the role of valproic acid in melanoma prevention,” the researchers said.