LanbotulinumtoxinA (LAN) was introduced in China. It is now available in Asia, Latin America and Eastern Europe under various brand names including Hengli®, Lantox®, Prosigne®, Lanzox®, Redux®, Liftox®, HBTX-A and CBTX-A.
1. Introduction
Botulinum toxin (BT) is produced by the anaerobic bacterium Clostridium botulinum. In the early 19th century, Justinus Kerner first recognised BT as the cause of botulism. In 1980, Alan B. Scott invented BT’s therapeutic use by applying it as a muscle relaxant for the treatment of strabismus in children [1]. In the meantime, BT’s use has expanded tremendously into numerous therapeutic indications and into widespread aesthetic use.
In China, the development of therapeutic BT started in 1985 by Professor Yinchun Wang at the Lanzhou Institute of Biological Products. Wang was trained by Edward J. Schantz at the University of Wisconsin in botulism research. In 1993, his product was approved by the Ministry of Health of the People’s Republic of China. This made China—after the USA and the UK—the third country in the world producing therapeutic BT. In 1997, the Lanzhou product was licensed by the Chinese Food and Drug Administration under the name lanbotulinumtoxinA (LAN, Lantox®; Lanzhou Institute of Biological Products, Lanzhou, China) as a drug for the treatment of strabismus, blepharospasm and hemifacial spasm. In 2012, this license was extended to moderate to severe glabellar frown lines. In 2002, LAN was successfully registered in South Korea. Since then, it has spread over Asia, Latin America and Eastern Europe, including major countries such as Brazil, India, Mexico and Russia [3][2]. LAN is available under various brand names such as Hengli®, Prosigne®, Lantox®, Lazox®, Redux®, Liftox®, HBTX-A and CBTX-A. In this entry, we will use LAN as the abbreviation of the generic name lanbotulinumtoxinA.
2. LanbotulinumtoxinA (LAN)
2.1. Motor Indications
2.1.1. Dystonia
Dystonia was—after strabismus and together with hemifacial spasm—the second group of indications developed. It is still the largest indication group for BT’s therapeutic use. Publications on blepharospasm also include the treatment of Meige syndrome, hemifacial spasm and sometimes cervical dystonia.
Table 1 shows two randomised controlled trials on LAN in blepharospasm. One of them [10][3] showed no difference in efficacy and safety between LAN and ONA. The other one [11][4] showed that sparing the medial lower eyelid improves tear film stability and lacrimal fluid drainage. One cross-over interventional study [12][5] found no difference in efficacy and safety between LAN and ONA.
Table 21.
LAN publications on dystonia and hemifacial spasm.
Authors |
I |
D |
n |
Methods |
Results |
Quagliato et al. [10] | Quagliato et al. [3] |
BS HFS |
RCT |
57 |
Comparing LAN and ONA. BS = 21, HFS = 36. LAN = 29, ONA = 28. LAN dose: ONA dose ratio = 1:1. Total BS dose: 60 MU. Total HFS dose: 35 MU |
No differences in efficacy and AE |
Lu et al. [11] | Lu et al. [4] |
BS |
RCT |
85 |
Comparing traditional injection sites and injection sites sparing medial lower eyelids |
Sparing medial lower eyelids improves tear film stability and lacrimal fluid drainage |
13 |
] |
SD-AD |
RCT |
27 |
Comparing LAN with a dose of 5 MU and LAN with a dose of 10 MU. Blitzer grade: ≥III. Blitzer dose: 25 MU/mL. EMG guidance. Unilateral thyroarytenoid injections |
No difference in onset time, time-to-peak effect and AE. Higher dose produces a longer effect duration |
Jiang & You [19] | Jiang & You [14] |
TMJD |
RCT |
90 |
Comparing semiconductor laser treatment and semiconductor laser treatment with LAN injection |
Semiconductor laser therapy with LAN has a better efficacy on inflammation and pain than semiconductor laser treatment alone. |
I, indication; D, design; n, number of patients/controls; RCT, randomised controlled trial; BS, blepharospasm; HFS, hemifacial spasm; CD, cervical dystonia; SD-AD, spasmodic dysphonia (adductor type); IS, interventional study; AE, adverse effects; LAN, Lantox
; TMJD, temporomandibular joint dysoorder.
Table 1 shows six selected randomised controlled trials for cervical dystonia. One study [8] compared LAN and ONA at a 1:1 dose conversion ratio, and one study [2] compared LAN and ABO at a 1:3 dose conversion ratio. Both studies did not find a difference in efficacy and safety between both drugs. One study [9] showed that LAN together with orthopaedic joint braces has a better efficacy than LAN alone, whereas oral drugs are not effective.
Table 1 shows the randomised controlled trial on adductor-type spasmodic dysphonia [13]. It was demonstrated that LAN with a dose of 10 MU produces longer effects than LAN with dose of 5 MU whereas peak efficacy and safety of these two doses are not different.
Table 1 shows the randomised controlled trial on temporomandibular joint disorders [14]. It was demonstrated that semiconductor laser therapy with LAN has better efficacy on inflammation and pain than semiconductor laser therapy alone.
2.1.2. Hemifacial Spasm
Table 1 shows two randomised controlled trials and two interventional studies on LAN for hemifacial spasm, one randomised controlled trial [10][3] and one interventional study [12][5] by comparing LAN and ONA, and no difference in efficacy and safety was found when converted on a LAN and ONA dose conversion ratio of 1:1. One randomised controlled trial [20][6] showed additional posterior auricular muscle injections can reduce acoustic symptoms, and one interventional study [21][7] showed that the LAN dose of 50 MU/mL produces longer therapeutic effects and more adverse effects than that of 25 MU/mL whereas the peak efficacies at these two doses are identical.
2.1.3. Tics
Overview over all lanbotulinumtoxinA (LAN) publications retrieved from Pubmed and Science and Technology Paper Citation Database.
Rieder et al. [ |
12 |
] | Rieder et al. [5] |
BS HFS |
IS |
26 |
Comparing LAN and ONA. Cross-over design. BS = 8, HFS = 18. LAN dose:ONA dose ratio = 1:1. Total dose: 2.5–5 MU per injection site |
Cervical dystonia | No differences in efficacy and AE |
N |
32 |
0 |
32 |
7 |
1 |
24 |
|
|
Peng et al. [20] | Peng et al. [6] |
HFS |
RCT |
63 |
Comparing effects of traditional injection sites and those of traditional injection sites with an additional dose of 4 MU in posterior auricular muscle (PAM). HFS with auricular symptoms |
Additional PAM injections reduce auricular symptoms |
Craniocervical dystonia |
N |
5 |
0 |
5 |
|
1 |
4 |
|
|
Li et al. [21] | Li et al. [7] |
HFS |
IS |
20 |
Comparing LAN with a dose of 50 MU/mL and LAN with a dose of 25 MU/mL. Cross-over design. LAN dose: 2.5–5 MU in each injection site. Washout period: 12 months |
No difference in efficacy. Longer duration and more AE with higher LAN concentration |
Writer’s cramp |
N |
2 |
0 |
2 |
|
|
2 |
|
|
Barbosa et al. [3] | Barbosa et al. [2] |
CD |
RCT |
34 |
Comparing LAN and ABO. ABO = 14. LAN = 20. ABO dose:LAN dose ratio = 3:1. Follow-up for 5 injection series every 3 months. |
No difference in efficacy, effect duration and AE |
Dystonias |
N |
11 |
1 |
12 |
|
|
12 |
|
|
Quagliato et al. [13] | Quagliato et al. [8] |
CD |
RCT |
24 |
Comparing LAN and ONA. LAN dose–ONA dose ratio = 1:1. Total dose: 300 MU |
No difference in efficacy, effect duration and AE |
Spasmodic dysphonia |
E |
3 |
0 |
3 |
1 |
|
2 |
|
|
Huang et al. [14] | Huang et al. [9] |
CD |
RCT |
105 |
Comparing oral drugs, LAN and LAN with orthopaedic joint brace (external fixator for head, neck, chest and back). Ultrasound guidance |
TMJ disorder | LAN with orthopaedic joint brace is better than LAN alone. Oral medication without efficacy |
N |
3 |
0 |
3 |
1 |
|
2 |
|
|
Wu et al. [15] | Wu et al. [10] |
CD |
RCT |
68 |
Comparing LAN with EMG guidance and LAN without EMG guidance. |
EMG guidance with prolonged efficacy and less AE, but more injection site pain. Maximal efficacies are not different. |
Hemifacial spasm |
N |
17 |
18 |
35 |
2 |
3 |
30 |
|
|
Hu et al. [16] | Hu et al. [11] |
CD |
RCT |
126 |
Comparing LAN with a dose of25 MU/mL and LAN with a dose of 17 MU/mL |
No difference in efficacy and AE |
Tics |
N |
1 |
Guidelines |
|
2 |
All |
351 |
28 |
379 |
71 |
41 |
232 |
15 |
20 |
S, medical specialty (A, aesthetics; E, ear, nose and throat; G, gastroenterology; N, neurology; O, ophthalmology; P, paediatrics; S, surgery; U, urology; PT, primary topic publication; ST, secondary topic publication; All, all publications; RCT, randomised controlled trial; IS, interventional study; OS, observational study; CS, case study; R, review; G, guideline; TMJ, temporomandibular joint.
2.1.4. Spasticity
2.1.7. Bladder Dysfunction
Table 3 shows three randomised controlled trials on bladder dysfunctons. One of them [39][16] showed that LAN is more effective in female overactive bladder than oral drugs, and one [40][17] showed that LAN with a dose of 200 MU including the trigonum and LAN with a dose of 300 MU excluding the trigonum produce identical efficacy and safety.
LAN publications on bladder dysfunctions.
Comparing LAN with a dose of 100 MU and oral drugs. Only females. Target muscle: detrusor excluding trigonum |
Comparing LAN with a dose of 200 MU including trigone and LAN with a dose of 300 MU excluding trigonum. Follow-up at 4 weeks |
No difference in efficacy and AE |
Comparing a LAN dose of 200 MU with electro-acupuncture and LAN alone. Transperineal application into external urethral sphincter |
Combined therapy is more effective. |
I, indication; D, design; n, number of patients/controls; RCT, randomised controlled trial; AE, adverse effects; LAN, Lantox ; OB, overactive bladder; NI, neurogenic Incontinence; NB, neurogenic bladder.
2.1.8. Gastroenterological Indications
2.2. Glandular Indications
2.2.1. Hyperhidrosis
LAN publications on glandular indications.
Comparing LAN with a dose of 200 MU and LAN with a dose of 50 MU |
A higher LAN dose has a longer efficacy. |
Comparing LAN and surgical gland excision |
LAN is more effective for mild and moderate BH and less effective for severe BH. |
Comparing LAN with electrical stimulation and electrical stimulation alone |
Combination therapy is more effective than electrical stimulation. |
LAN with a dose of 200 MU was injected into five points at the lateral and middle lobes of the prostate under the guidance of ultrasound with a balloon dilatational device. |
All symptoms and indicators are improved and maintained for a period of at least 1 year. |
Luo et al. [ |
17 |
] |
Luo et al. |
[ |
12 |
] |
CD |
RCT |
27 |
Comparing LAN with a dose of 50 MU/mL and LAN with a dose of 12.5 MU/mL |
No difference in efficacy and AE |
Spasticity |
N |
40 |
0 |
40 |
18 |
7 |
14 |
1 |
|
Hu et al. [18] | Hu et al. [ |
Cerebral Palsy |
P |
38 |
0 |
38 |
16 |
7 |
15 |
|
|
Strabismus |
O |
17 |
1 |
18 |
1 |
2 |
15 |
|
|
Bladder dysfunction |
U |
8 |
0 |
8 |
3 |
1 |
4 |
|
|
Gastroparesis |
G |
1 |
0 |
1 |
|
|
|
1 |
|
Achalasia |
G |
2 |
0 |
2 |
|
|
|
2 |
|
Oesophageal strictures |
G |
1 |
0 |
1 |
1 |
|
|
|
|
Dysphagia |
G |
1 |
0 |
1 |
|
|
|
1 |
|
Anismus |
S |
1 |
0 |
1 |
|
|
1 |
|
|
Raynaud syndrome |
N |
1 |
0 |
1 |
|
|
|
1 |
|
Tinnitus |
E |
1 |
0 |
1 |
|
|
|
1 |
|
Glandular indications |
Hyperhidrosis |
N |
11 |
0 |
11 |
2 |
2 |
7 |
|
|
Sialorhea |
N |
4 |
0 |
4 |
1 |
|
3 |
|
|
Prostate hyperplasia |
U |
1 |
0 |
1 |
|
|
|
1 |
|
Pain indications |
Migraine |
N |
20 |
0 |
20 |
7 |
2 |
11 |
|
|
Trigeminal neuralgia |
N |
9 |
0 |
9 |
3 |
2 |
3 |
1 |
|
Postherpetic neuralgia |
N |
3 |
0 |
3 |
1 |
|
1 |
1 |
|
Aesthetic indications |
Wrinkles |
A |
36 |
1 |
37 |
5 |
2 |
30 |
|
|
Calf reduction |
A |
6 |
0 |
6 |
|
1 |
5 |
|
|
Masseter reduction |
A |
2 |
0 |
2 |
|
|
2 |
|
|
Scars |
A |
2 |
0 |
2 |
|
|
1 |
1 |
|
Acne |
A |
1 |
0 |
1 |
|
|
|
1 |
|
Methods |
Drug comparison |
3 |
0 |
3 |
|
2 |
1 |
|
|
Remote effects |
1 |
0 |
1 |
|
1 |
|
|
|
Allergic reactions |
2 |
0 |
2 |
|
|
|
2 |
|
Reviews and guidelines |
Reviews |
|
18 |
I, indication; D, design; n, number of patients/subjects; RCT, randomised controlled trials; AE, adverse effects; LAN, Lantox
; AH, axillar hyperhidrosis; S, sialorhea; BH, bromhidrosis; BPH, benign prostatic hyperplasia.
2.2.2. Sialorrhea
2.3.3. Prostate Hyperplasia
As shown in Table 4, one observational study [22] suggested the effect of LAN on benign prostate hyperplasia. The mechanism involved remains unclear.
2.4. Pain Indications
2.5. Aesthetic Indications