Duration Of Clinical Efficacy Of OnabotulinumtoxinA-Purified Neurotoxin Complex In Crow's Feet Lines

PURPOSE

This analysis determined the duration of clinical response to onabotulinumtoxinA treatment of crow’s feet lines (CFL) based on 2 large, double-blind, placebo-controlled phase 3 studies.

DESIGN

Subjects in studies 1 and 2 had moderate or severe CFL on entry and received 24U onabotulinumtoxinA in CFL. Subjects entering study 2 also had moderate or severe glabellar lines (GL) and could be randomized to receive 20U in GL for a total dose of 44U. Response was based on investigator- and subject-evaluated Facial Wrinkle Scale (FWS) scores at maximum smile and at rest at day 30, where responder is defined as achieving a ≥1-point improvement in FWS. Median durations of clinical effect for treatment responders at day 30 were calculated using the Kaplan-Meier method.

RESULTS

The studies enrolled 1362 subjects; 833 received onabotulinumtoxinA in the crow’s feet region (222 study 1; 611 study 2). In study 2, 305 subjects received an additional 20U in glabella for a total dose of 44U. Follow-up was 150 and 120 days in studies 1 and 2, respectively. Study 2 had a higher percentage of subjects with severe dynamic CFL at baseline and an older population.

In study 1, median durations of effect for responders were 125 and 144 days for dynamic lines and 137 and 148 days for static lines as assessed by investigator and subject, respectively. The longest recorded duration of efficacy was 164 days (capped due to study duration). In study 2, median duration of efficacy of both dynamic and static lines was 119-121 days as assessed by investigator or subject. The longest recorded duration of efficacy in study 2 was 172 days. 

Median Duration of Treatment Response (Days)
Study	1	2
	ONA 24U (N=222)	ONA 44U (N=305)	ONA 24U (N=306)
Dynamic; ≥1-Grade Change
Subject	144.0 (n=173)	119.0 (n=232)	119.0 (n=206)
Investigator	125.0 (n=190)	120.0 (n=268)	119.0 (n=239)
Static; ≥1-Grade Change
Subject	148.0 (n=139)	121.0 (n=190)	120.0 (n=189)
Investigator	137.0 (n=141)	120.0 (n=220)	120.0 (n=182)

ONA, onabotulinumtoxinA; N=subjects receiving injections; n=responders at day 30.

SUMMARY

Median durations of response were ≥4 months for all onabotulinumtoxinA treatment arms in both studies, based on responder definition. The lower responder rate and duration in study 2 is most likely related to the higher baseline CFL wrinkle severity and the 120-day follow-up period.