Anthony M. Rossi, MD
Dr. Rossi is a Fellow in Procedural Dermatology and Mohs Surgery, Memorial Sloan-Kettering and Weill Cornell/New York-Presbyterian Hospital, both in New York, New York.
Dr. Rossi reports no conflicts of interest in relation to this post.
The September 2012 issue of Dermatologic Surgery (2012;38:1497-1505) featured a randomized double-blind study to compare the safety, efficacy, and dose-response relationship of 2 doses of onabotulinumtoxinA for the treatment of hyperdynamic perioral rhytides. Sixty female participants were randomized in a 1:1 ratio to receive either 7.5 or 12.0 U of onabotulinumtoxinA at 4 perioral sites. Participants were then assessed at weeks 2, 4, 8, 12, 16, and 20. The severity of the perioral lines and participant satisfaction were assessed at all visits. A treatment response was deemed as having a reduction of at least 1 point on the investigator assessment of perioral line severity scale at maximum contraction (0=none, no lines; 1=mild, few shallow lines; 2=moderate, some moderate lines; 3=severe, many deep lines or crevices) at week 4. The investigators treated both the upper and lower lips for symmetry but only evaluated the 4 injection points of the upper lip. The investigators found that both groups had experienced reduced severity in perioral lines, but the 12.0-U group experienced reduction through week 20 (P<.01) and the 7.5-U group through week 16 (P<.05). The responder rates did not differ until week 12 (12.0 U, 77%; 7.5 U, 36%; P=.003). Participant satisfaction peaked at week 8 (7.5 U, 73%; 12.0 U, 81%). Compared to the 12-U group, satisfaction with 7.5 U was greater at weeks 2, 12, 16, and 20. Mean participant-assessed lip satisfaction total score significantly improved from baseline (P<.05) to all time points for both groups, except at week 20 (12.0 U, P=.06). Most adverse events were reported as mild to moderate in severity and typical for onabotulinumtoxinA treatment in the lips. The incidence was found to be dose dependent. Typical adverse events included weakness of the lips, numbness, trouble eating, lip dryness, lip fullness, and lip swelling. All adverse events for the 7.5-U dose resolved without sequelae or follow-up by 50 days into the study. For the 12.0-U dose, 1 participant experienced decreased mobility of the lips. At study termination, follow-up continued for patients with dryness of the lips, influenzalike syndrome, bruising of the left upper lip, and decreased mobility of the mouth in 2 participants.
What’s the issue?
Since onabotulinumtoxinA is not approved by the US Food and Drug Administration for treatment of the lips or perioral area, dosing has been based on individual clinical experience with few published studies. The evaluation of muscle mass for dosing purposes is more difficult in the perioral area and additionally the desired outcome is weakness of the orbicularis oris muscle instead of complete paralyzation. Therefore, the dosing of onabotulinumtoxinA is not as straightforward. This study compared 2 different dosing parameters for the treatment of hyperdynamic perioral rhytides and concluded that both 7.5- and 12.0-U doses yielded significant reductions in investigator-assessed perioral rhytide severity for 16 and 20 weeks, respectively. However, a significant difference in responder rates between the 2 doses was only reported at week 12, suggesting that duration of effectiveness was not dose dependent. Similarly, satisfaction rates were not shown to be dose dependent, which strengthens an argument to use the lowest possible dose when treating the perioral area. This assertion also echoes that more adverse events and ones that required follow-up were experienced in the 12.0-U dose group. In 2008, a consensus statement regarding the treatment of perioral lines recommended a dose of 4 to 5 U of onabotulinumtoxinA (Carruthers JD, Glogau RG, Blitzer A; Facial Aesthetics Consensus Group Faculty. Advances in facial rejuvenation: botulinum toxin type A, hyaluronic acid dermal fillers, and combination therapies—consensus recommendations. Plast Reconstr Surg. 2008;121[suppl 5]:5S-30S). Overall, a conservative approach is recommended when treating hyperdynamic perioral rhytides and initial conservative dosing is warranted to avoid the risk for adverse sequelae. For patients with both dynamic and static perioral rhytides, a combinatorial approach with neurotoxin, hyaluronic acid filler, and laser therapy may be best. Again, a lower dose of onabotulinumtoxinA would be warranted in this scenario.