What is the evidence for efficacy and safety of onabotulinumtoxin A in treating craniofacial hyperhidrosis?

Comment by InpharmD Researcher

Data on the use of onabotulinumtoxin A in treating craniofacial hyperhidrosis are primarily limited to case reports and case series. Additionally, two small studies, one prospective trial and one randomized pilot study, report a high success rate with botulinum toxin A use with temporary adverse events. Please refer to Table 1 for a summary of relevant primary literature examining use of onabotulinumtoxin A.

Background

A 2023 systematic review summarized evidence for efficacy and safety of botulinum toxin in the treatment of various scalp conditions, including alopecia, craniofacial hyperhidrosis, and scalp hyperseborrhea. A total of 24 studies (N= 309 patients) reported data on the use of botulinum toxin A and B, of which craniofacial hyperhidrosis was reported in 53 patient cases that were treated with botulinum toxin A (BTX-A). In two case reports and two case series describing 14 patients with craniofacial sweating, 71.4% of patients had reduced sweating after BTX-A treatment. In another case series of 11 patients, the duration of response to therapy lasted ~5 months on average. As data are limited to case series and case studies, and are not specific to onabotulinumtoxin A, more robust evidence is required to further understand efficacy and safety. [1]

A 2015 systematic review compiled evidence regarding treatment of primary craniofacial hyperhidrosis. A total of 27 studies were included, two of which evaluated intradermal injection of BTX-A. One of these was a prospective uncontrolled study (rated as evidence level III; N= 10 patients) and the other was a small double-blind randomized pilot study (level Ib; N= 20 patients). These studies are summarized in Table 1, along with other relevant primary literature. Both of these studies observed a 100% success rate, with transient adverse effects (frontalis muscle inhibition). Though the relevant data are limited by small sample sizes, treatment with BTX-A was considered to be an important therapeutic option for management of craniofacial hyperhidrosis. [2]

References:

[1] Nguyen B, Perez SM, Tosti A. Botulinum Toxin for Scalp Conditions: A Systematic Review. Dermatol Surg. 2023;49(11):1023-1026. doi:10.1097/DSS.0000000000003895
[2] Nicholas R, Quddus A, Baker DM. Treatment of Primary Craniofacial Hyperhidrosis: A Systematic Review. Am J Clin Dermatol. 2015;16(5):361-370. doi:10.1007/s40257-015-0136-6
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What is the evidence for efficacy and safety of onabotulinumtoxin A in treating craniofacial hyperhidrosis?

Level of evidence

D - Case reports or unreliable data  Read more→


Please see Table 1 for your response.

 

Summary of Studies Evaluating Onabotulinumtoxin A in Treating Craniofacial Hyperhidrosis

Citation

Design

Outcome and Methods

Efficacy

 Safety

Kinkelin et al. (2000)

N= 10

OnaBTX-A, injected intracutaneously at a mean dosage of 86 mouse units

 Effectiveness on frontal hyperhidrosis assessed at T0 and after 4 weeks by:
- Minor’s iodine-starch test
- Gravimetric assessment
- Photograph

The mean amount of sweat was significantly reduced, 4 weeks after treatment, from 173.8 mg/min to 53.7 mg/min (p< 0.005).

Reduction of sweat after 4 weeks of treatment lasted up to 5 months in 9 out of 10 patients.

 Painful injections and a transient weakness of forehead muscles without ptosis

Trindade et al. (2007)

N= 20

All patients received two injections of BoNTA1 (BOTOX, Allergan, Inc.) on one side of their forehead (3 IU per injection) plus two injections of BoNTA2 (Dysport, Ipsen Ltd.) on the other side of their forehead (patients were randomly assigned to receive 7.5, 9, or 12 IU per injection) at a dose ratio of 1:2.5, 1:3, or 1:4.

 Effectiveness on frontal hyperhidrosis evaluated at baseline, 24 hours, 1 week, 2 weeks, and 1, 2, 3, 4, 5, and 6 months. During the 6 months after treatment, the area of anhidrosis was larger with BoNTA2 in 93% (195/210) of medial-medial or lateral-lateral comparisons of the two products and at all dose ratios. The smaller area of anhidrosis with BoNTA1 did not compromise its efficacy in inhibiting the contraction of the frontalis muscle. Minimizing the area of diffusion is important to minimize the potential for adverse events AEs.

Komericki and Ardjomand (2012)

N= 1

Case report of a 52-year-old male with extensive craniofacial hyperhidrosis

A 100-unit vial of OnaBTX-A was reconstituted in 5mL of saline and injected intradermally at 300 injection points across the upper forehead and scalp at a 10-20 mm distance between injection points.
Injections performed 2 times per year

Sweating assessed using starch-iodine test

 Sweating completely stopped after treatments Slight transient bleeding at injection sites that disappeared within 5 days

Ko EJ et al. (2014)

N= 2

OnaBTX-A injected on the right of forehead (3.3 IU),
AboBTX-A injected on the middle (8.3 IU)
PraBTX-A injected on the left (3.3 IU)
All injections were of identical volume (0.1 mL)

 Comparison of the efficacy and diffusion of three formulations of botulinum toxin type A in three different areas of the forehead by the following assessments at T0 and after 2 weeks:
- Minor iodine–starch test
- Transepidermal water loss (TEWL)
- Corneometer		 The area of diffusion appears to be greater with AboBTX-A covering 6.7% of the total area, while OnaBTX-A and PraBTX-A produced similarly sized areas of anhidrosis (2.5% and 2.6%, respectively). Minimizing the area of diffusion is important to minimize the potential for AEs.

George et al. (2014)

N= 4

OnaBTX-A injected using a dose of 1–2 units per injection

Effectiveness on rarer forms of focal facial hyperidrosis (upper lip and chin, both cheeks, central face, and frontal scalp respectively) assessed at T0 and after 6 weeks by Minor’s iodine-starch test 

 Reduction of sweat, lasted at mean 6–8 months after treatment. 

Patient with frontal hyperhidrosis: loss of rhytides on her forehead and mild brow ptosis

Patient with perioral sweating: droop of his left upper lip

Park et al. (2021)

N= 1

Case report of a 32-year-old female with 5-year history of hyperhidrosis most severe in the face and scalp

A 5 mL injection of 100 units of OnaBTX-A mixed with 2 mL lidocaine and 8 mL normal saline injected into the stellate ganglion on each side

Ultrasound was used to assist needle guidance into stellate ganglion

 		 Sweating reduced at 6-month follow-up No AEs reported
Abbreviations: AE, adverse events; Onabotulinum toxin type A, OnaBTX-A; Abototulinum toxin type A (AboBTX-A); Prabobotulinum toxin type A (PraBTX-A)
References:

[1] Kinkelin I, Hund M, Naumann M, Hamm H. Effective treatment of frontal hyperhidrosis with botulinum toxin A. Br J Dermatol. 2000;143(4):824-827. doi:10.1046/j.1365-2133.2000.03839.x
[2] Trindade de Almeida AR, Marques E, de Almeida J, Cunha T, Boraso R. Pilot study comparing the diffusion of two formulations of botulinum toxin type A in patients with forehead hyperhidrosis. Dermatol Surg. 2007;33(1 Spec No.):S37-S43. doi:10.1111/j.1524-4725.2006.32330.x
[3] Ko EJ, Mun SK, Oh IY, Kwon TR, Kim BJ, Kim MN. Comparison of efficacy and diffusion of three formulations of botulinum toxin type A in two patients with forehead hyperhidrosis. Clin Exp Dermatol. 2014;39(5):673-675. doi:10.1111/ced.12362
[4] George SM, Atkinson LR, Farrant PB, Shergill BS. Botulinum toxin for focal hyperhidrosis of the face. Br J Dermatol. 2014;170(1):211-213. doi:10.1111/bjd.12568
[5] Komericki P, Ardjomand N. Hyperhidrosis of face and scalp: repeated successful treatment with botulinum toxin type A. Indian J Dermatol Venereol Leprol. 2012;78(2):201-202. doi:10.4103/0378-6323.93647
[6] Park JH, Kim R, Na SH, Kwon SY. Effect of botulinum toxin in stellate ganglion for craniofacial hyperhidrosis: a case report. J Int Med Res. 2021;49(3):3000605211004213. doi:10.1177/03000605211004213