Botulinum Toxin A: Treatment of Hyperhidrosis

Transcription

1 Botulinum Toxin A: Treatment of Hyperhidrosis Dee Anna Glaser, M.D. FAAD Professor Interim Chairman Director of Cosmetic & Laser Surgery Department of Dermatology Professor ENT & Internal Medicine Saint Louis University AAD 2018

2 Research Disclosures Allergan Brickell Dermira Evolus Galderma Ulthera Revance Advisor/consultant Discussion off-label uses Allergan Galderma Dermira Glaser

3 Glaser

4 1.6 to 4 million glands Average density varies Sweating Back 64 glands/cm 2 Forehead 181 glands/cm 2 Palms/soles 700 glands/cm 2 Sympathetic nervous system Acetylcholine Sato K et al. J Am Acad Dermatol. 1989;20: Glaser

5 Current Treatments for Primary Focal Hyperhidrosis Topical agents Systemic agents Tap water iontophoresis (TWI) Botulinum toxin type A (BTX-A) injections Microwave technology Surgery Sweat gland resection, liposuction, curettage Endoscopic transthoracic sympathectomy (ETS) Hornberger J, et al. J Am Acad Dermatol. 2004;51(2): Glaser

6 Botulinum Toxin Therapy BTX A Excellent efficacy and safety Onabot- FDA-approval July 19, 2004 for severe primary axillary hyperhidrosis Abobot -used in other parts of world Incobot reported efficacy BTX B limited numbers of patients treated Systemic side effects reported Glaser

7 Primary Endpoint Reduce the impact of hyperhidrosis on patient s lives Reduce HDSS scores from 4 or 3 to 2 or 1 Impact of sweating on daily activities 4=intolerable, always interferes 3=barely tolerable, frequently interferes 2=tolerable, sometimes interferes 1=never noticeable, never interferes

8 U.S. 52-Week Phase 3 Trial 52-week, multicenter, double-blind, randomized, placebo-controlled, dose-ranging, parallel-group study Both axillae were injected with onabotulinumtoxina 50 U, 75 U, or placebo Patients assessed at 4-week intervals Patients were eligible for re-injection no sooner than 8 weeks after the previous treatment if they met the initial inclusion criteria N = 322 patients BTX-A 50 U (n = 104) BTX-A 75 U (n = 110) Placebo (n = 108)

9 Patient Characteristics Characteristic BTX-A 50 U (n = 104) Treatment BTX-A 75 U (n = 110) Placebo (n = 108) Total (N = 322) White ethnicity 84% 78% 82% 81% Sex, M/F 55/45% 55/45% 53/47% 54/46% Mean age, years Severity at baseline (HDSS) Glaser

10 Patients (%) Patients With At Least a 2-Grade Improvement in HDSS Score ***P.0001 vs placebo *** 74 *** *** *** N=48 BTX-A 50 U BTX-A 75 U Placebo N=104 N=110 N= N=108 N=68 0 Treatment 1 Treatment 2 Lowe NJ, Glaser DA, Eadie N, et al. JAAD 56:604-11, 2007 Intent to treat analysis; includes imputation for missing values

11 Patients (%) Patients With At Least a 75% Reduction in Sweat Production *** 84 *** ***P.0001 vs placebo BTX-A 50 U BTX-A 75 U Placebo Lowe NJ, Glaser DA, Eadie N, et al. JAAD 56:604-11, 2007 Intent to treat analysis; includes observed data only

12 Treatment Satisfaction 100 Patients who were much more satisfied with the study treatment compared to previous treatments Patients (%) % 84% (73/86) (75/89) 20 0 BTX-A 50U BTX-A 75U 20% (17/87) Placebo Item: Compared to treatments you have used before this study, how satisfied are you overall with this study treatment? Response options: Much more satisfied, Somewhat more satisfied, Neutral, Somewhat less satisfied, Much less satisfied

13 Safety Profile of OnabotulinumtoxinA No serious treatment-related adverse events were reported The majority of side effects were mild in severity No clinically significant changes in laboratory values, findings on physical examination, or vital signs were reported Incidence of adverse events not significantly different between groups Adverse event* BTX-A 50 U (n = 104) Patients with event BTX-A 75 U (n = 110) Placebo (n = 108) Injection site pain 12% 9% 8% Injection site bleeding 5% 6% 3% Non-axillary sweating 10% 6% 4% *Most frequent adverse events (>5%)

14 Duration of Treatment Response OnabotA treatment effect was durable Approximately 25% of patients in each OnabotA group required only 1 treatment through week 52 OnabotA -treated with > 2-grade decrease in HDSS score had lengthy durations of response as shown in table below Median Duration (days) Patients with >2-grade decrease in HDSS Treatment 1 Treatment 2 50 U U Glaser et al. Am Acad Neurol Meeting, 2004

15 Axillary Hyperhidrosis 145 patients 200 units of abobotulinumtoxina in one axilla, placebo in the other Gravimetric testing at baseline, 2 and 24 weeks mgs/min BTX A Placebo Baseline weeks weeks Heckmann. J AM Acad Dermatol 1999;41:987 Glaser

16 Starch Iodine Test

17

18 Minor s Iodine Starch Test Glaser

19 BTX-A Axillary Injections Reconstitute 4 cc saline 30 gauge ½ inch needle 50 units (2 cc) per axilla Deep dermal Glaser

20 Glaser

21 Consider increased dose if results are not adequate or of long enough duration Glaser

22 Hyperhidrosis: Botulinum Toxin Therapy Other body areas can be treated Off label Reconstitute 2-4 cc saline 30 gauge ½ inch needle Deep dermal Dosing and pain control

23 Dosing Pain Control Duration Muscle weakness Palmar Hyperhidrosis

24 Palmar Hyperhidrosis Dosing 2-3 units u/hand Ulnar side Pain Control Duration Muscle weakness

25 Pain Control: Palmar Injections Topical anesthesia Nerve blocks Beir Block Cold anesthesia Vibration General / IV sedation anesthesia Grin and Bear It

26

27

28 Hyperhidrosis: Botulinum Toxin Therapy Axillary on label All body areas can be treated Reconstitute 2-4 cc saline 30 gauge ½ inch needle Deep dermal Dosing and pain control Can be combined with other therapies for optimal outcomes

29 International Hyperhidrosis Society