Long-Term Post-Marketing Surveillance Database Review of Delayed-Onset Events with Resilient Hyaluronic Acid Dermal Fillers

Abstract Background Delayed-onset events (DOEs) after hyaluronic acid (HA) filler injection are rare complications occurring weeks to months after treatment and characterized by inflammatory nodules, swelling, and erythema. In clinical trials and previous analyses, resilient hyaluronic acid (RHA) gels have demonstrated an excellent safety profile with no or low incidence of DOEs, but more recent real-world data are lacking. Objectives To investigate the incidence of DOEs with RHA gels since product launch using post-marketing safety surveillance data. Methods A retrospective review of the Revance US post-marketing safety database between June 2020 and December 2024 identified events occurring >2 weeks post-injection that matched descriptive terms associated with DOEs. A parallel search of the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database captured events across FDA-approved HA fillers over the same period. Results Overall reported DOE rate for RHA fillers was 0.009% (1 per 10,925 syringes), with formulation-specific rates ranging from 0.003% to 0.018%. Most events presented as nodules (57.6%) and/or swelling (50.2%); granulomas were rare (0.0001% per syringe distributed). Events most frequently occurred >4 weeks to ≤4 months after treatment (49%). Hyaluronidase, with or without corticosteroids, was the most common treatment. The FDA MAUDE database analysis identified 1283 reports across 22 FDA-approved HA fillers matching specified search terms for DOEs; of those, 81 were with RHA fillers (6.3%). Conclusions RHA fillers demonstrate a low rate of DOEs in real-world use. The small number of RHA reports identified in MAUDE was consistent with the observed internal reporting pattern.