Treatment of hyperhidrosis with Botox (onabotulinumtoxinA): Development, insights, and impact

Abstract

Hyperhidrosis (chronic excessive sweating) may substantially affect an individual's emotional and social well-being. Therapies available before onabotulinumtoxinA were generally topical, with limited effectiveness, application-site skin reactions, and frequent, time-consuming treatments. Intradermal injection of onabotulinumtoxinA to treat sweat glands arose as a novel therapeutic approach. To develop this treatment, appropriate dosing needed to be established, and training on administration was required. Further, no previous scale existed to measure the effects of hyperhidrosis on patients' lives, leading Allergan to develop and validate the 4-point Hyperhidrosis Disease Severity Scale (HDSS), which measures the disease's impact on daily activities. The onabotulinumtoxinA clinical development program for hyperhidrosis included 2 double-blind, placebo-controlled pivotal trials, immunogenicity studies, long-term studies of safety and efficacy, and quality of life assessments. In Europe and North America, the primary efficacy measures were, respectively, axillary sweat production measured gravimetrically and HDSS improvement. Compared with placebo, onabotulinumtoxinA treatment significantly reduced axillary sweat production and axillary hyperhidrosis severity, as measured by a 2-point or greater reduction on the HDSS. The effects of onabotulinumtoxinA occurred rapidly, within 1 week after injection, and lasted ≥6 months. Treatment with onabotulinumtoxinA was associated with significant quality of life improvements based on Short Form-12 physical and mental component scores. The Hyperhidrosis Impact Questionnaire also indicated greater treatment satisfaction, reduced negative impact on aspects of daily life, and improved emotional well-being with onabotulinumtoxinA versus placebo. The clinical development program and subsequent clinical experience showed that onabotulinumtoxinA treatment for hyperhidrosis was well tolerated with no new safety signals, and led to greater disease awareness.

Figure 1.

Mean DLQI scores for hyperhidrosis relative to other skin conditions.^[4] DLQI = Dermatology Quality of Life Index.

Figure 2.

Proportion of patients changing clothing ≥2 times per day because of excessive sweating from hyperhidrosis.^[5] *P < .001 versus placebo. OnabotA = onabotulinumtoxinA.

Figure 3.

Axillary hyperhidrosis (A) before and (B) 2 weeks after onabotulinumtoxinA treatment, documented by the Minor starch–iodine test. Adapted with permission from: Naumann M, et al.^[37]

Figure 4.

Proportion of subjects with at least a 50% reduction from baseline in axillary sweat, measured gravimetrically at weeks 1, 4, and 16.^[33] *P < .001 versus placebo.

Figure 5.

Effect on sweat production of botulinum toxin type A versus placebo.^[33] *P < .001 versus placebo.

Figure 6.

Key outcomes in the US/Canadian study. Week 4 data figure adapted with permission from: Lowe NJ, et al.^[46] Hyperhidrosis Disease Severity Scale (My underarm sweating is: [A] never noticeable and never interferes with my daily activities; [B] tolerable but sometimes interferes with my daily activities; [C] barely tolerable and frequently interferes with my daily activities; [D] intolerable and always interferes with my daily activities). *P < .001 for both onabotulinumtoxinA doses versus placebo. ^†P < .01 for both onabotulinumtoxinA doses versus placebo. HDSS = Hyperhidrosis Disease Severity Scale.

Figure 7.

Percent reduction from baseline in axillary sweat production, measured gravimetrically.^[46] *P < .001 versus placebo.