Botulinum Toxins: 2019 Update
Michael S. Kaminer, MD
Botulinum toxins have an increasing number of approved indications and off-label uses, not only in aesthetic medicine and neuromuscular disorders, but also in ophthalmologic, urologic, gastrointestinal, hypersecretory, and pain disorders.1 Several important pharmacological properties contribute to their utility: they are very potent and neurospecific toxins; when injected locally, their diffusion is limited; and their action reverses over time.2 When used to minimize glabellar frown lines and other facial wrinkles, the full effect develops in about 1 to 2 weeks. Benefit lasts about 4 months, or longer in some cases.3
Approved Toxins
Conversion Factor
The first botulinum A toxin (onabotulinumtoxinA) was approved in the United States for cosmetic use in 2002. Three more toxins have been introduced since that time, including 1 in February 2019 (Table).4-10 The dose of incobotulinumtoxinA is equivalent to that of onabotulinumtoxinA in published studies,11,12 although some clinicians disagree. Multiple studies12 have reported a dose conversion factor from onabotulinumtoxinA or incobotulinumtoxinA to abobotulinumtoxinA of 1:3; many clinicians use a conversion factor of 1:2.5. Relative potency of the investigational toxin daxibotulinumtoxinA compared with onabotulinumtoxinA has not been established.13

Highlights of the 43rd Annual Hawaii Dermatology Seminar
This journal supplement is intended for dermatologists, nurse practitioners, registered nurses, physician assistants, and other clinicians who practice medical dermatology and aesthetic medicine.
Supported by educational grants from:
Ortho Dermatologics, LEO Pharma Inc., and Galderma Laboratories, L.P.
Activity Information
Expired
Original Release Date: August 2019
Expiration Date: August 31, 2021
Estimated Time to Complete Activity: 2.0 hours
Expired
Participants should read the activity information, review the activity in its entirety, and complete the online post-test and evaluation. Upon completing this activity as designed and achieving a passing score on the post-test, you will be directed to a Web page that will allow you to receive your certificate of credit via e-mail or you may print it out at that time.
The online post-test and evaluation can be accessed at https://tinyurl.com/HDS19Supp.
Inquiries about continuing medical education (CME) accreditation may be directed to the University of Louisville Office of Continuing Medical Education & Professional Development (CME & PD) at [email protected] louisville.edu or 502-852-5329.
CME/CE Accreditation Statements
Physicians: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the University of Louisville School of Medicine and Global Academy for Medical Education, LLC. The University of Louisville School of Medicine is accredited by the ACCME to provide continuing education for physicians.
The University of Louisville School of Medicine designates this enduring activity for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Nurses
Joint Provider Accreditation Statement
In support of improving patient care, this activity has been planned and implemented by Postgraduate Institute for Medicine and Global Academy for Medical Education, LLC. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the health care team.
Continuing Nursing Education
The maximum number of hours awarded for this Continuing Nursing Education activity is 2.5 contact hours. Designated for 2.4 hours of pharmacotherapy credit for advanced practice nurses.
Educational Needs
Dermatologists can benefit from education on recent developments in many areas of clinical practice. In psoriasis treatment, nearly all patients are prescribed topical therapies. New medications using improved vehicles and fixed-dose combinations have become available, and more are in development. New research linking psoriasis and risk of cardiovascular disease has provided a better understanding of the underlying pathological mechanism and the potential benefit of anti-inflammatory treatment. Recent epidemiologic data on atopic dermatitis in adults have important implications for diagnosis and treatment. In acne treatment, several efficacious systemic treatments are underutilized, and education on their risks and benefits may improve clinical practice. In the treatment of skin cancer, dermatologists should consider several systemic treatments in addition to surgery. Finally, a new botulinum toxin became available recently, and others are in development.
Learning Objectives
At the conclusion of this activity, participants should be better able to:
- Describe recent data on psoriasis treatment, including new vehicles for topical treatments, fixed-dose combination therapies, and investigational topical medications
- Review the relationship between psoriasis and cardiovascular disease (CVD) and the potential effects of psoriasis treatment on CVD risk
- Describe current research on the temporal patterns of atopic dermatitis onset and resolution and the differences in diagnosis and treatment approach for adult and pediatric patients
- Analyze the efficacy and safety of systemic therapies for acne
- Assess the current nonsurgical treatments for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and localized melanoma
- Review the options for confirming the diagnosis and data on the use of topical and systemic treatments in the management of onychomycosis
- Assess the advantages and disadvantages of available botulinum toxins used to address patient concerns about facial aging
Disclosure Declarations
Individuals in a position to control the content of this educational activity are required to disclose: (1) the existence of any relevant financial relationship with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients with the exemption of nonprofit or government organizations and non–health-carerelated companies, within the past 12 months; and (2) the identification of a commercial product/device that is unlabeled for use or an investigational use of a product/device not yet approved.
Nathaniel J. Jellinek, MD, has indicated he has nothing to disclose.
Michael S. Kaminer, MD, has indicated he is a Consultant for Artic Fox, Cutera, Cytrellis, Endo, L’Oréal, Soliton, and Zeltiq.
Alan Menter, MD, has indicated he is on the Speakers Bureau for AbbVie, Celgene, Eli Lilly, Janssen, Novartis, and OrthoDoc.
Jonathan I. Silverberg, MD, PhD, MPH, has indicated he is on the Speakers Bureau for Regeneron/Sanofi; is a Consultant, and/or Advisory Board member for AbbVie, AnaptysBio, Asana, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Kiniksa, LEO, Menlo, Pfizer, Realm, and Regeneron Sanofi; and has received Grant/Contracted Research Support from GlaxoSmithKline.
Linda F. Stein Gold, MD, has indicated she is on the Speakers Bureau for Galderma, LEO, Mayne, Pfizer, Sanofi/Regeneron, Taro, and Valeant; is a Consultant for Foamix, Galderma, LEO, Mayne, Menlo, Pfizer, Sanofi/ Regeneron, Sol-Gel, Taro, and Valeant; and has received Grant/Contracted Research Support from Foamix, Janssen, LEO, Menlo, Pfizer, and Valeant.
Christopher B. Zachary, MBBS, FRCP, has indicated he is a Consultant for Allergan, Candela, Sciton, and Solta.
University of Louisville CME & PD Advisory Board and Staff Disclosures: The University of Louisville CME & PD Advisory Board and office staff have nothing to disclose, with the following Board Member exceptions: Sathya Krishnasamy, MD – Novo Nordisk (Grant Funding); Ashlee Bergin, MD – Merck Pharmaceuticals (Speaking); Michael Sowell, MD – Amgen (Speaking) and Impax Pharmaceuticals (Grant Funding); Rainer Lenhardt, MD – CSL Behring, Mallinckrodt, and Merck (Speaking).
CME/CE Reviewers: Courtney R. Schadt, MD, Assistant Professor of Medicine, Chief of Dermatology, University of Louisville School of Medicine, Louisville, Kentucky, has nothing to disclose.
Postgraduate Institute of Medicine planners and managers have nothing to disclose.
Global Academy for Medical Education Staff: Shirley V. Jones, MBA; Eileen A. McCaffrey, MA; and Margaret McLaughlin, PhD, have nothing to disclose.
Off-Label/Investigational Use Disclosure
This CME/CE activity discusses the off-label use of certain approved medications as well as data from clinical trials on investigational agents. Such material is identified within the text of the articles.
References
- Gart MS, Gutowski KA. Overview of botulinum toxins for aesthetic uses. Clin Plast Surg.2016;43(3):459-471.
- Pirazzini M, Rossetto O, Eleopra R, Montecucco C. Botulinum neurotoxins: biology, pharmacology, and toxicology. Pharmacol Rev. 2017;69(2) 200-235.
- Small R. Botulinum toxin injection for facial wrinkles. Am Fam Physician. 2014;90(3):168-175.
- Dysport [package insert]. Fort Worth, TX: Galderma Laboratories, L.P.: July 2016.
- Xeomin [package insert]. Raleigh, NC; Merz Pharmaceuticals, LLC; July 2018.
- Sattler G, Callander MJ, Grablowitz D, et al. Noninferiority of incobotulinumtoxinA, free from complexing proteins, compared with another botulinum toxin type A in the treatment of glabellar frown lines. Dermatol Surg. 2010;36(suppl 4):2146-2154.
- Botox Cosmetic [package insert]. Madison, NJ: Allergan USA, Inc; May 2018.
- Jeuveau [package insert]. Santa Barbara, CA: Evolus Inc; February 2019.
- Rzany BJ, Ascher B, Avelar RL, et al. A multicenter, randomized, double-blind, placebocontrolled, single-dose, phase III, non-inferiority study comparing prabotulinumtoxinA and onabotulinumtoxinA for the treatment of moderate to severe glabellar lines in adult subjects. Aesthet Surg J. 2019 April 5 [Epub ahead of print].
- Benedetto AV. What’s new in cosmetic dermatology. Dermatol Clin. 2019;37(1):117-128.
- Jandhyala R. Relative potency of incobotulinumtoxinA vs onabotulinumtoxinA a meta-analysis of key evidence. J Drugs Dermatol. 2012;11(6):731-736.
- Samizadeh S, De Boulle K. Botulinum neurotoxin formulations: overcoming the confusion. Clin Cosmet Investig Dermatol. 2018;11:273-287.
- Carruthers J, Solish N, Humphrey S, et al. Injectable daxibotulinumtoxinA for the treatment of glabellar lines: a phase 2, randomized, dose-ranging, double-blind, multicenter comparison with onabotulinumtoxinA and placebo. Dermatol Surg. 2017;43(11):1321-1331.
- Beer KR, Shamban AT, Avelar RL, Gross JE, Jonker A. Efficacy and safety of prabotulinumtoxinA for the treatment of glabellar lines in adult subjects: results from 2 identical phase III studies. Dermatol Surg. 2019 March 18 [Epub ahead of print].
- Yoelin SG, Dhawan SS, Vitarella D, Ahmad W, Hasan F, Abushakra S. Safety and efficacy of EB-001, a novel type E botulinum toxin, in subjects with glabellar frown lines: results of a phase 2, randomized, placebo-controlled, ascending-dose study. Plast Reconstr Surg. 2018;142(6):847e-855e.
- Ascher B, Rzany B, Kestemont P, et al. Liquid formulation of abobotulinumtoxinA: a 6-month, phase 3, double-blind, randomized, placebo-controlled study of a single treatment, ready-to-use toxin for moderate-to-severe glabellar lines. Aesthet Surg J. 2019 March 20 [Epub ahead of print].
Disclosures
Michael S. Kaminer, MD, has indicated he is a Consultant for Artic Fox, Cutera, Cytrellis, Endo, L’Oréal, Soliton, and Zeltiq.