How does Botox directly compare to Xeomin?

Comment by InpharmD Researcher

While both onabotulinumtoxinA and incobotulinumtoxinA are effective botulinum toxin type A (BoNTA) preparations, they possess distinct pharmacological profiles due to differences in their molecular structures and production methods. OnabotulinumtoxinA has been shown to have a greater effect and longer duration than incobotulinumtoxinA, but it also carries a higher risk of adverse events. However, the two formulations have demonstrated comparable efficacy and safety profiles within clinical trials for treating various conditions, including glabellar lines, cervical dystonia, and neurogenic incontinence, suggesting either can serve as a viable option in clinical practice.

Background

A 2018 review provided a critical appraisal of the pharmacological distinctions and clinical implications of the three commercially available botulinum toxin serotype A (BoNTA) preparations: onabotulinumtoxinA (Botox), abobotulinumtoxinA, and incobotulinumtoxinA (Xeomin). Botox and abobotulinumtoxinA include botulinum neurotoxin protein complexes of varying molecular weights, with the former consisting of a 900 kDa complex and the latter a 400 kDa complex. In contrast, Xeomin is a purified 150 kDa neurotoxin devoid of accessory proteins. These structural differences, combined with distinct production and stabilization methods, result in non-interchangeable products with specific pharmacokinetics, dosing requirements, and clinical applications. Notably, potency evaluations revealed variations in neurotoxin load per 100 units, with specific neurotoxin potency values calculated as 137 units/ng for Botox and 227 units/ng for Xeomin. Pharmacological studies suggest that Botox has a greater effect and longer duration compared to Xeomin but also predisposes Botox to a greater risk of adverse events. Ultimately, the choice of BoNTA should be individualized per patient, reinforced by the pharmacotherapeutic profiles of each product. [1]

A 2022 network meta-analysis of 18 randomized controlled trials (RCTs) involving 4,706 participants investigated the efficacy and safety of various BoNTA formulations for treating moderate-to-severe glabellar lines. The analysis involved six BoNT/A formulations, including Botox and Xeomin. Outcomes Assessed the proportion of participants achieving a glabellar line severity score of none or mild at maximal frown by one month, at least 1-point or 2-point improvement on standardized scales, and related adverse events (AEs). The analysis demonstrated that all BoNT/A formulations significantly outperformed placebo in achieving aesthetic improvement, with daxibotulinumtoxinA showing the highest efficacy. While incremental differences in 2-point improvement efficacy were noted, statistical significance was not achieved for this metric. Safety outcomes indicated a low incidence of adverse events across all formulations, and no significant differences were observed between BoNT/A products, although all formulations carried higher risk than placebo. Ranking probabilities using SUCRA identified daxibotulinumtoxinA as the most effective, while Botox typically ranked above Xeomin. [2]

A 2016 analysis systematically evaluated the efficacy and safety of botulinum toxin formulations for the treatment of cervical dystonia (CD) using a Bayesian mixed treatment comparison (MTC) model. The analysis incorporated data from 11 RCTs involving 1,295 participants and focused on five botulinum toxin including Botox and Xeomin. According to the Bayesian analysis, Botox, Xeomin, and the other three BoTNs demonstrated significant efficacy compared to placebo, with median improvements in The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores ranging between -5.78 and -8.22 across the five BoNT. Xeomin appears to have demonstrated the greatest effect in TWSTRS total scores but was not statistically different from the other toxins. Overall, the comparable efficacy and safety profiles of Dysport and Xeomin in managing cervical dystonia were similar, affirming their utility as potential first-line options in clinical practice. [3]

References:

[1] Ferrari A, Manca M, Tugnoli V, Alberto L. Pharmacological differences and clinical implications of various botulinum toxin preparations: a critical appraisal. Funct Neurol. 2018;33(1):7-18. doi:10.11138/fneur/2018.33.1.007
[2] Li X, Sui C, Xia X, Chen X. Efficacy and Safety of Botulinum Toxin Type A for Treatment of Glabellar Lines: A Network Meta-Analysis of Randomized Controlled Trials. Aesthetic Plast Surg. 2023;47(1):365-377. doi:10.1007/s00266-022-03018-y
[3] Han Y, Stevens AL, Dashtipour K, Hauser RA, Mari Z. A mixed treatment comparison to compare the efficacy and safety of botulinum toxin treatments for cervical dystonia. J Neurol. 2016;263(4):772-780. doi:10.1007/s00415-016-8050-2

Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

How does Botox directly compare to Xeomin?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→



Please see Tables 1-5 for your response.


 

IncobotulinumtoxinA versus onabotulinumtoxinA intradetrusor injections in patients with neurogenic detrusor overactivity incontinence: a double-blind, randomized, non-inferiority trial

Design

Double-blind, randomized, non-inferiority trial

N= 64

Objective

To compare the efficacy, safety and related costs of IncobotulinumtoxinA (ncobot/A) versus Onabot/A for the treatment of refractory neurogenic detrusor overactivity incontinence (NDOI) in patients affected by spinal cord injury (SCI) and multiple sclerosis (MS) performing intermittent catheterization (C)

Study Groups

IncobotulinumtoxinA (n= 28)

OnabotulinumtoxinA (n= 29)

Inclusion Criteria

Patients aged 18-80 with SCI or MS, experiencing at least 2 UI episodes per day, refractory to at least one pharmacological agent, under a chronic regimen of daily IC, and naïve to Onabot/A and Incobot/A treatments.

Exclusion Criteria

SCI above T1 level, EDSS Score ≥6 (MS only), pregnancy or breastfeeding, previous/current hematuria, bladder diseases, previous bladder-altering surgeries, and use of certain pharmacological agents.

Methods

Participants received 30 intradetrusor injections of either Incobot/A or Onabot/A 200 U. Procedures were performed under local anesthesia with a single dose of antibiotic administered before injection.

Duration

12 weeks follow-up.

Outcome Measures

Primary: Change in daily UI episodes at week 12

Secondary: Visual analog scale (VAS) scores (bother of urinary symptoms on quality of life), urodynamic parameters, occurrence of adverse effects

Baseline Characteristics

 

IncobotulinumtoxinA (n= 28)

OnabotulinumtoxinA (n= 29)

   

Age, years

51 53    

Female

15 18    

SCI

MS

16

12

17

12

   

Disease duration, years

9.5 9    

Expanded Disability Status Scale

4.2 4.5    

Daytime urinary frequency

Nighttime urinary frequency

9.1

3.4

9.4

3.8

   

Urinary incontinence, episodes/day

7.1 6.7    

Bladder emptying

IC

Only IC

IC + spontaneous voiding

 

28

24

4

 

29

25

4

   

Acetycholine use, No. of patients

67.8%

68.9%

   

Results

Endpoint

IncobotulinumtoxinA (n= 28) OnabotulinumtoxinA (n= 29)

Difference (95% confidence interval [CI])

p-Value

Daily UI

Baseline

Week 12

 

7.1 ± 2.2

2.0 ± 1.6

 

6.7 ± 2.4

2.2 ± 1.7

 

0.4 (-0.8 to 1.6)

-0.2 (-1.0 to 0.7)

 

0.35

0.73

VAS score

Baseline

Week 12

 

8.0 ± 1.3

3.3 ± 1.9

 

7.9 ± 1.4

3.8 ± 2.3

 

0.1 (-0.6 to 0.8)

-0.4 (-1.6 to 0.7)

 

0.82

0.61

Urodynamic results

Baseline

Week 12

 

257 (146 to 294)

420 (334 to 500)

 

244 (191 to 304)

390 (314 to 500)

 

-7 (-47 to 33)

20 (-27 to 66)

 

0.71

0.46

Adverse Events

Urinary tract infections, asymptomatic bacteriuria, hematuria, bladder/urethral pain, constipation, diarrhea, asthenia, flu-like syndrome/nasopharyngitis, and fever were reported. No significant difference between the two toxins.

Study Author Conclusions

IncobotulinumtoxinA was not inferior to OnabotulinumtoxinA in improving clinical and urodynamic findings in patients with refractory neurogenic incontinence due to SCI or MS, with comparable adverse effects but minor costs.

InpharmD Researcher Critique

The study was well-designed with a clear objective and robust methodology. However, the sample size was relatively small, and the follow-up duration was short. The study was also impacted by the Sars-Cov-2 pandemic, which may have influenced the results. Further larger-scale studies with longer follow-up are needed to confirm these findings.



References:

Giannantoni A, Gubbiotti M, Rubilotta E, Balzarro M, Antonelli A, Bini V. IncobotulinumtoxinA versus onabotulinumtoxinA intradetrusor injections in patients with neurogenic detrusor overactivity incontinence: a double-blind, randomized, non-inferiority trial. Minerva Urol Nephrol. 2022;74(5):625-635. doi:10.23736/S2724-6051.21.04227-2

 

A Direct Comparison of OnabotulinumtoxinA (Botox) and IncobotulinumtoxinA (Xeomin) in the Treatment of Benign Essential Blepharospasm: A Split-face Technique

Design

Prospective, randomized, double-blinded split-face study

N= 48

Objective

To evaluate and compare the efficacy of onabotulinumtoxinA (Botox) and incobotulinumtoxinA (Xeomin) in the treatment of benign essential blepharospasm (BEB)

Study Groups

Study patients (N= 48)

Inclusion Criteria

Patients with bilateral, symmetrical BEB previously treated and controlled with Botox.

Exclusion Criteria

N/A

Methods

Patients received 4 injections of either Xeomin or Botox on each side of the face. The side of the face in which they received treatment was randomized and masked from the investigator and patients. Each visit, patients would answer the Blepharospasm Disability Index (BSDI) and choose a preferred treatment side. Orbicularis strength and spasm, as well as evaluation using Jankovic Rating Scale (JRS) was performed.

Duration

4 treatment visits with follow-up after the last injection.

Outcome Measures

Patient preference, BSDI scores, JRS scores, residual orbicularis strength and spasm

Baseline Characteristics

 

Study patients (N= 48)

     

Age, years

70.2      

Female

24      

Age at symptom onset, years

56.8      

Duration of treatment before study, years

17.0      

Units used per side

19.9      

Results

Endpoint

Mean BSDI

Mean JRS

Residual strength

Residual spasm

Xeomin

Visit 1

Visit 5

 

4.70 ± 1.40

3.79 ± 1.42

 

2.81 ± 0.34

2.64 ± 0.39

 

-1.04 ± 0.21

-1.19 ± 0.20

 

1.41 ± 0.20

1.44 ± 0.20

Botox

Visit 1

Visit 5

 

5.19 ± 1.43

4.19 ± 1.56

 

2.83 ± 0.35

2.64 ± 0.39

 

-1.03 ± 0.21

-1.20 ± 0.18

 

1.42 ± 0.20

1.47 ± 0.22

Adverse Events

No adverse events were reported in the study.

Study Author Conclusions

No difference between Xeomin and Botox was detected in either subjective or objective measures for the treatment of BEB.

InpharmD Researcher Critique

The study's strengths include its randomized, double-blind design and the use of a split-face technique, which controls for individual variability. Limitations include the potential insensitivity of the BSDI and JRS scales to detect subtle differences between the two treatments, and the lack of detailed exclusion criteria.



References:

Saad J, Gourdeau A. A direct comparison of onabotulinumtoxina (Botox) and IncobotulinumtoxinA (Xeomin®) in the treatment of benign essential blepharospasm: a split-face technique. J Neuroophthalmol. 2014;34(3):233-236. doi:10.1097/WNO.0000000000000110

 

A Randomized, Double-Blind Trial to Investigate the Equivalence of IncobotulinumtoxinA and OnabotulinumtoxinA for Glabellar Frown Lines

Design

Prospective, multicenter, randomized, double-blind, parallel-group study

N= 250

Objective

To investigate the dose equivalence of incobotulinumtoxinA (20 U) and onabotulinumtoxinA (20 U) for the treatment of moderate-to-severe glabellar frown lines (GFL)

Study Groups

IncobotulinumtoxinA (n= 122)

OnabotulinumtoxinA (n= 128)

Inclusion Criteria

Female subjects aged 18 to 50 years with moderate-to-severe GFL at maximum frown (severity score of 2 or 3 on the 4-point Facial Wrinkle Scale).

Exclusion Criteria

Severe FWS score at rest, previous BoNT treatment in the upper face within 6 months, previous filler treatment in the glabellar area, facial surgery or scars, facial nerve palsy, severe or uncontrolled systemic disease, hypersensitivity to study drugs, pregnancy, or nursing.

Methods

Patients received a single treatment with 20 U of either incobotulinumtoxinA or onabotulinumtoxinA, administered in equal aliquots to 5 injection points in the procerus and corrugator muscles. Followed by a 4-month observational period.

Duration

4-month follow-up period with assessments at 1, 2, 3, and 4 months after injection.

Outcome Measures

Primary: 1-point improvement on the Facial Wrinkle Scale (FWS) at maximum frown at 1 month (a prespecified equivalence margin of ±15% was used to determine clinical equivalency)

Secondary: FWS clinical response at 2, 3, and 4 months; patient satisfaction

Baseline Characteristics

  IncobotulinumtoxinA (n= 122)

OnabotulinumtoxinA (n= 128)

 

Age, years

39.3 39.4  

Female

122 128  

Ethnicity

Hispanic/Latino

Not Hispanic/Latino

 

18.9%

81.1%

 

27.3%

72.7%

 

Race

White

Black/African American

Asian

American Indian or Alaska Native

Other

 

85.2%

11.5%

3.3%

0

0

 

83.6%

10.2%

3.1%

0.8%

2.3%

 

Baseline FWS score at max frown

Rated by masked panel

Rated by physician

 

2.5

2.5

 

2.5

2.6

 

Results

Endpoint

IncobotulinumtoxinA (n= 122)

OnabotulinumtoxinA (n= 128) Treatment difference (95% confidence interval [CI])

1-point improvement on the Facial Wrinkle Scale (FWS) at maximum frown at 1 month

95.7% 99.2% -3.5% (-7.5% to 0.6%)

FWS response rate

2 month

3 month

4 month

 

89.7

80.2

62.1

 

95.0

80.7

67.2

 

-5.3 (-12.1 to 1.5)

-0.5 (-10.6 to 9.6)

-5.2 (-17.4 to 7.1)

Patient satisfaction at 4 months

93.0

90.4

 

Adverse Events

Similar percentage of subjects experienced at least one treatment-emergent adverse event (TEAE) in both groups. Most TEAEs were mild or moderate. Two serious TEAEs were reported, both unrelated to the study drug. No AESI in the incobotulinumtoxinA group and two in the onabotulinumtoxinA group.

Study Author Conclusions

Equivalence was demonstrated between incobotulinumtoxinA and onabotulinumtoxinA for the treatment of GFL at the 20 U dose at 1 month. Similar efficacy and tolerability profiles were observed through 4 months after treatment.

InpharmD Researcher Critique

The study's strengths include its randomized, double-blind design and the use of FDA-recommended doses. Limitations include the focus on a female-only population and the lack of power to demonstrate equivalence at 4 months. The study confirms previous findings of equivalence but does not address potential differences in long-term outcomes or in diverse populations.



References:

Kane MA, Gold MH, Coleman WP 3rd, et al. A Randomized, Double-Blind Trial to Investigate the Equivalence of IncobotulinumtoxinA and OnabotulinumtoxinA for Glabellar Frown Lines. Dermatol Surg. 2015;41(11):1310-1319. doi:10.1097/DSS.0000000000000531

 

Noninferiority of IncobotulinumtoxinA, Free from Complexing Proteins, Compared with Another Botulinum Toxin Type A in the Treatment of Glabellar Frown Lines

Design

Prospective, multicenter, nonrandomized, rater- and patient-blind, international Phase III trial

N= 381

Objective

To investigate the noninferiority of incobotulinumtoxinA to another botulinum toxin type A, onabotulinumtoxinA, in the treatment of glabellar frown lines

Study Groups

IncobotulinumtoxinA (n= 284)

OnabotulinumtoxinA (n= 97)

Inclusion Criteria

Women aged 18 to 50 with moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on the Facial Wrinkle Scale).

Exclusion Criteria

Severe glabellar frown lines at rest, previous botulinum toxin treatment in the upper third of the face within 6 months, biodegradable fillers in the glabellar area within 12 months, permanent material in the glabellar area, surgery or scars in the glabellar area, marked facial asymmetry or ptosis, and any medical condition that may pose a risk with botulinum toxin exposure.

Methods

Patients were randomized (3:1) to receive 24 U of incobotulinumtoxinA or onabotulinumtoxinA. Five intramuscular injections were administered: 0.15 mL (6 U) in the procerus muscle, 0.125 mL (5 U) in the medial part of each corrugator muscle, and 0.1 mL (4 U) in the middle part of each corrugator muscle. Efficacy assessed by independent raters and investigators using standardized digital photographs.

Duration

12 weeks, with a 1-week additional screening period.

Outcome Measures

Primary: Percentage of responders at maximum frown at week 4 (improvement of 1 point on a 4-point facial wrinkle scale [FWS])

Secondary: Percentage of responders at maximum frown at week 12, patient's global assessment (PGA) of change in appearance

Baseline Characteristics

 

IncobotulinumtoxinA (n= 284)

OnabotulinumtoxinA (n= 97)

Age, years

41.7 42

White

99.3% 98.9%

Received at least one previous botulinum toxin treatment the past 6 months for facial lines

30.3% 30.1%

Facial wrinkle scale score at rest

Mild

Moderate

 

33.3%

62.8%

 

34.4%

60.2%

Facial wrinkle scale score at max frown

Mild

Moderate

 

32.5%

67.5%

 

29.0%

71.0%

Results

Endpoint

IncobotulinumtoxinA (n= 284)

OnabotulinumtoxinA (n= 97)

Percentage of responders at maximum frown at week 4

Independent

Investigator

 

41.5%

75.8%

 

39.8%

71.0%

Percentage of responders at maximum frown at week 12

Independent

Investigator

 

36.1%

59.9%

 

35.5%

54.8%

PGA week 4

93.5%

92.5%

Adverse Events

Low incidence of adverse events. Treatment-emergent adverse events (TEAEs) occurred in 19.4% of incobotulinumtoxinA group and 26.8% of onabotulinumtoxinA group. Headache was the most frequent TEAE related to treatment. Eyelid ptosis occurred in one patient in the onabotulinumtoxinA group and resolved.

Study Author Conclusions

IncobotulinumtoxinA is as effective as onabotulinumtoxinA in treating glabellar frown lines over at least 12 weeks. Both preparations were well tolerated, with high patient satisfaction rates.

InpharmD Researcher Critique

Strengths include a large sample size and a well-structured head-to-head comparison. Limitations include the age restriction to 50 years and limited ethnic diversity, which may affect the generalizability of the results. Statistical investigations were not performed.



References:

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. doi:10.1111/j.1524-4725.2010.01706.x

 

Efficacy and safety of incobotulinum toxin A in periocular rhytides and masseteric hypertrophy: side-by-side comparison with onabotulinum toxin A

Design

Randomized, double-blind, split-face study

N= 112

Objective

To compare the efficacy and safety of incobotulinum toxin A with onabotulinum toxin A in treating periocular rhytides and masseteric hypertrophy

Study Groups

Periocular rhytides (n= 56)

Masseteric hypertrophy (n= 56)

Inclusion Criteria

Patients with periocular wrinkles and masseteric hypertrophy, approval of institutional review board, informed consent.

Exclusion Criteria

Previous treatment with filler, BT injection, or photorejuvenation within 6 months, use of topical tretinoin or retinol-containing cosmetics, pregnancy, active nursing, preexisting neuromuscular conditions, drug allergy, serious medical disorders, medications affected by BT injection.

Methods

Incobotulinum and onabotulinum were injected on opposite sides of the face. For periocular rhytides, 7.5 U injected into orbicularis oculi muscles. For masseteric hypertrophy, 25 U injected into the masseter muscle. Digital photographic documentation and assessments using Fitzpatrick Wrinkle Classification System (FWCS) and 10-point visual analogue scale (VAS).

Duration

16 weeks follow-up for both periocular rhytides and masseteric hypertrophy groups.

Outcome Measures

Primary: Fitzpatrick Wrinkle Classification System (FWCS), Visual Analogue Scale (VAS)

Secondary: Onset time of effect, adverse events

Baseline Characteristics

 

Periocular rhytides (n= 56)

Masseteric hypertrophy (n= 56)  

Age, years

43.4 31.8  

Female

94.6% 89.3%  

Results

Endpoint

IncobotulinumtoxinA OnabotulinumtoxinA p-Value

Investigator-ranked FWCS on periocular rhytides

Week 1

Week 16

 

3.25 ± 1.93

1.82 ± 1.99

 

3.64 ± 1.74

1.91 ± 1.98

 

0.12

0.29

Patient-ranked VAS on periocular rhytides

Week 1

Week 16

 

3.45 ± 2.00

2.05 ± 1.85

 

3.41 ± 2.05

2.05 ± 2.01

 

0.78

0.98

Investigator-ranked FWCS on masseteric hypertrophy

Week 1

Week 16

 

2.71 ± 1.45

2.46 ± 2.16

 

2.89 ± 1.64

2.78 ± 2.04

 

0.21

0.06

Patient-ranked VAS on masseteric hypertrophy

Week 1

Week 16

 

2.64 ± 1.54

2.41 ± 1.69

 

2.59 ± 1.65

2.43 ± 1.91

 

0.74

0.91

Adverse Events

No adverse events reported during and after treatment up to 16 weeks.

Study Author Conclusions

Incobotulinum toxin A provided non-inferior efficacy and safety compared to onabotulinum toxin A for the treatment of periocular rhytides and masseteric hypertrophy.

InpharmD Researcher Critique

The study's strengths include its randomized, double-blind design and the use of objective and subjective measures. Limitations include the short follow-up period and the lack of long-term data on the development of neutralizing antibodies.



References:

Lee JH, Park JH, Lee SK, et al. Efficacy and safety of incobotulinum toxin A in periocular rhytides and masseteric hypertrophy: side-by-side comparison with onabotulinum toxin A. J Dermatolog Treat. 2014;25(4):326-330. doi:10.3109/09546634.2013.769041