A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Repeat Treatments of Crow's Feet Lines and Glabellar Lines with Onabotulinumtoxina

Friday, April 12, 2013
Jean Carruthers, MD1, Alexander Rivkin, MD2, Lisa Donofrio, MD3, Vince Bertucci, MD, FRCPC4, Christine Somogyi5, Elisabeth Lee, MPH5, Xiaofang Lei, PhD5, Dawn Schiele5 and Frederick Beddingfield, MD, PhD5, (1)Division of Dermatology, University of British Columbia, Vancouver, DC, Canada, (2)Division of Dermatology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, (3)Department of Dermatology, Yale University School of Medicine, New Haven, CT, (4)Department of Medicine, University of Toronto, Toronto, ON, Canada, (5)Allergan Inc, Irvine, CA
Goals/Purpose: To assess efficacy and safety of repeated onabotulinumtoxinA treatments of crow’s feet lines (CFL) with or without glabellar (GL) lines for up to 1 year.

Methods/Technique: This 1-year assessment was a double-blind, placebo-controlled (DBPC), 7-month study plus a DBPC, 5-month extension study. Subjects with moderate-to-severe CFL and GL (at maximum contraction using the Facial Wrinkle Scale with Photonumeric Guide [FWS]; 0=none to 3=severe) initially received 2 treatment cycles of onabotulinumtoxinA or placebo (PBO) 120 days apart. Subjects who had received onabotulinumtoxinA 24U (CFL only, n=227) or 44U (24U in CFL + 20U in GL, n=260) continued in their original treatment group, while PBO-treated subjects were re-randomized to onabotulinumtoxinA 44U (CFL+GL, n=101) or PBO (n=96) for up to 2 more treatment cycles. Retreatment in the 5-month extension per criteria: 1) ≥3 months since last treatment and 2) investigator-assessed CFL and GL of at least moderate severity. The primary efficacy endpoint was CFL FWS severity at maximum smile on day 30 after the first treatment (treatment 3) in the extension study (primary timepoint). Responders were those with a CFL severity rating of none or mild at maximum smile. Other endpoints were CFL severity at rest and maximum smile at all time points, GL severity, and patient-reported outcomes (PROs), including Subject’s Global Assessment of Change in CFL (SGA-CFL). Adverse events (AEs) were monitored.

Results/Complications: 684 subjects entered the extension study. CFL responder rates (RRs) were significantly greater in the onabotulinumtoxinA-treated groups (24U CFL: 56.5%; 44U CFL+GL: 63.6%; PBO: 1.1%; P<.001). RRs on most PROs at day 30 favored the 44U CFL+GL group over the 24U CFL group. The proportions reporting very much or much improved on the SGA-CFL were significantly higher in onabotulinumtoxinA groups (CFL: 56.5%; CFL+GL: 59.6%; PBO: 5.3%; P<.001). Subjects reporting very satisfied or satisfied with appearance at primary timepoint were 52.5%, 58.3%, and 7.5% in CFL, CFL+GL, and PBO groups (P<.001). The incidence of AEs did not differ significantly among groups; most AEs were mild or moderate. No subjects discontinued due to AEs.

Conclusion: Repeated onabotulinumtoxinA treatments of CFL alone or concurrently with GL are associated with significantly reduced CFL severity as well as significantly higher subject satisfaction and additional PROs. The safety profile was consistent with the approved GL indication.