Efficacy, safety, and patient-reported outcomes following onabotulinumtoxinA treatment for moderate-to-severe forehead lines: a pooled analysis of two Phase III pivotal trials

Presenters: De Boulle K¹, Fagien S², Mao C³, Shumate GT³, Gallagher CJ³

Affiliations: ¹Aalst Dermatology Clinic, Aalst, Belgium; ²Aesthetic Eyelid Plastic Surgery, Boca Raton, FL; ³Allergan plc, Irvine, CA

Background/Objective: Two pivotal, Phase III studies were conducted to evaluate the safety and efficacy of onabotulinumtoxinA (onabotA) versus placebo (PBO) for treatment of moderate-to-severe forehead lines (FHL).

Methods: In both studies, neurotoxin-naïve subjects were randomized to receive onabotA 40U (frontalis 20U, glabella 20U) or PBO. The second study included an additional treatment arm in which bilateral crow’s feet regions (CFL) were also treated for a total dose of 64U (FHL 20U, GL 20U, CFL 24U) or PBO. After Day 180, all eligible subjects could receive up to two additional open-label onabotA treatments, with assessments to Day 360. Dynamic and static FHL were assessed at all timepoints by both investigator and subject using the Facial Wrinkle Scale with photo numeric guide. Subject satisfaction with treatment was evaluated using the validated Facial Lines Satisfaction Questionnaire (FLSQ).

Results: This pooled analysis comprised 1,178 subjects in the intent-to-treat (ITT) population (onabotA 40U n=608, onabotA 64U n=313; PBO n=257). At maximum eyebrow elevation, Day 30 responder rates for those achieving more than a 2-grade composite FHL improvement based on investigator and subject FWS were 53.1 (40U) and 53.0 (64U) percent, respectively. Responder rates for those achieving more than a 1-grade FHL improvement were 97.9 (40U) and 99.0 (64U) percent, respectively. Percentage of subjects achieving a score of none/mild FHL were 92.3 (40U) and 94.9 (64U) percent, respectively. Of those subjects with at least mild static FHL at baseline, 85.4 (40U) and 84.8 (64U) percent achieved more than a 1-grade improvement at rest. Efficacy and patient satisfaction were comparable across treatment cycles. Based on the FLSQ, 85.6 (40U) and 87.9 (64U) percent of subjects reported being mostly satisfied or very satisfied with the effect treatment had on their forehead lines at Day 60. Across all treatment cycles over 12 months, 25.4 percent of subjects had treatment-related adverse events; of note were brow ptosis (2.6%) and lid ptosis (1.8%). Most frequently reported treatment-emergent adverse events included headache (11.8%), injection site bruising (7.4%), nasopharyngitis (8.3%), and upper respiratory tract infection (4.3%). No new safety signals were detected with repeated upper facial line treatments.

Conclusion: OnabotA significantly improved the appearance of FHL. Treatment of upper facial lines was well tolerated with efficacy and patient satisfaction maintained across repeat treatments.