Is there any comparative data suggesting superiority for Botox over Xeomin for Xeomin's FDA-approved indications? Is there data on switching patients from Botox to Xeomin?

Comment by InpharmD Researcher

Based on comparative data, Botox may not be clinically superior to Xeomin for their shared FDA-approved indications, as studies consistently demonstrate non-inferiority or equivalent efficacy and safety between the two. Some analyses, such as a 2022 network meta-analysis, show Botox typically ranking above Xeomin for glabellar lines, but these incremental differences are not statistically significant. Regarding immunogenicity, a 2025 review suggests Xeomin (incobotulinumtoxinA) may have a lower risk of secondary treatment failure, particularly in neurological conditions requiring long-term, high-dose treatment. Data on switching patients from Botox to Xeomin indicates it is generally well-tolerated and effective, allowing for successful transition without exacerbating adverse effects.

botox xeomin

Background

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. [1]

A 2025 systematic review and meta-analysis assessed secondary treatment failure (STF) and immunogenicity associated with Botulinum Neurotoxin A (BoNT-A) across multiple neurological conditions. The investigation focused on three commercially available formulations: abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA, analyzing their use in conditions such as cervical dystonia (CD), spasticity, and blepharospasm. The findings were derived from a comprehensive analysis of 29 unique studies obtained through a detailed search in PubMed, Embase, and Google Scholar. This detailed meta-analysis revealed that patients treated with abobotulinumtoxinA or onabotulinumtoxinA exhibited a notably higher incidence of STF and neutralizing antibody (NAb) positivity compared to those treated with incobotulinumtoxinA, particularly among individuals with CD or spasticity. Intriguingly, no cases of STF or persistent NAbs were identified in patients treated exclusively with incobotulinumtoxinA. The investigation further highlighted that the risk of developing STF and NAbs appeared to increase with higher mean doses of abobotulinumtoxinA or onabotulinumtoxinA. This comprehensive review suggests that among BoNT-A formulations, incobotulinumtoxinA may be recommended to avoid immunogenic STF, especially for patients requiring high doses and repeated treatments, thus highlighting its favorable profile in minimizing the risk of immunogenicity in long-term treatment scenarios. [2]

A 2025 retrospective analysis assessed botulinum toxin switching in the management of spasticity across a cohort of 206 patients. Carried out following reimbursement adjustments in France, the investigation aimed to assess tolerance and efficacy associated with brand switches of botulinum toxin, a procedure not frequently explored given the typical consistency of toxin brands in treatment. The study observed that the majority of patients transitioned from Botox to Xeomin (73.66%), while smaller proportions shifted from Botox to Dysport (14.63%), or from Xeomin to Dysport (11.71%). Dose adjustments varied with these switches, particularly from Botox to Xeomin, which displayed the greatest diversity in dosage changes. Despite these modifications, the study reported good tolerance overall, with minimal adverse effects, mainly fatigue. The perceived efficacy varied among patients, with some noting improvements and others experiencing a decline, although the median efficacy remained stable. The analysis highlighted the importance of personalized treatment and indicated that switching between botulinum toxin brands could be accomplished without exacerbating adverse effects. A significant portion of the study participants (57.06%) chose to continue with the new toxin treatment post-switch, demonstrating relative satisfaction, although 42.93% preferred to revert to their original treatment. The data suggested that while differences were observed between the groups, these variations were not statistically significant. Furthermore, the study pointed to potential placebo and nocebo effects influencing perceived efficacy and side effects during treatment transitions. Overall, the findings underscore the benefits of individualized therapeutic approaches and careful monitoring when implementing botulinum toxin changes for spasticity management.

References: [1] 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
[2] Walter U, Albrecht P, Carr W, Hefter H. Systematic Review and Meta-Analysis of Secondary Treatment Failure and Immunogenicity With Botulinum Neurotoxin A in Multiple Indications. Eur J Neurol. 2025;32(8):e70289. doi:10.1111/ene.70289
[3] Leblong E, Piette P, Anne C, et al. Switox: Retrospective Analysis of Botulinum Toxin Switching in Management of Spasticity. Toxins (Basel). 2025;17(3):103. Published 2025 Feb 24. doi:10.3390/toxins17030103
Literature Review

A search of the published medical literature revealed 11 studies investigating the researchable question:

Is there any comparative data suggesting superiority for Botox over Xeomin for Xeomin's FDA-approved indications? Is there data on switching patients from Botox to Xeomin?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-11 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:
[1] 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:
[1] 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:
[1] 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:
[1] 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:
[1] 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

Switchover study of onabotulinumtoxinA to incobotulinumtoxinA for facial dystonia
Design

Retrospective study of a prospective, single-masked switchover audit

N= 38
Objective To evaluate switching from OnabotulinumtoxinA to incobotulinumtoxinA in the treatment of essential blepharospasm (EB), hemifacial spasm (HFS) and aberrant facial nerve regeneration (AFR)
Study Groups

Essential EB (n= 20)

HFS (n= 12)

AFR (n= 6)
Inclusion Criteria Patients who had achieved stable dosing on OnabotulinumtoxinA prior to the switchover with a diagnosis of EB, HFS and AFR
Exclusion Criteria Patients not on a stable dosing regimen of OnabotulinumtoxinA prior to switchover; patients who enquired about the brand of botulinum A; those unresponsive/intolerant of OnabotulinumtoxinA and on another brand
Methods A switchover from stable OnabotulinumtoxinA to IncobotulinumtoxinA was conducted using a 1:1 unit ratio. Two nurse injectors performed the injections over a period of 6 years. Each masked patient received 3 OnabotulinumtoxinA and 3 IncobotulinumtoxinA over a minimum of 2 years. 
Duration Minimum of 2 years
Outcome Measures

Primary: Blepharospasm disability score (BDS), Jankovic score (JS)

Secondary: Subjective improvement, duration of maximum effect (DME), complications
Baseline Characteristics   Essential EB (n= 20) HFS (n= 12) AFR (n= 6)
Mean age, years Not specified Not specified Not specified
Results   OnabotulinumtoxinA IncobotulinumtoxinA p-value
Subjective improvement in HFS 72% 84% <0.01

Duration of maximum effect, weeks

EB

HFS

 

14

11

 

12

12

 

NS

<0.05

Complications

Bruising

Ptosis

13%

2

3

3%

1

0

-

-

-

Most results were presented as graphs. No significant differences were noted for BDS or JS between groups. 
Adverse Events See above
Study Author Conclusions Switching from OnabotulinumtoxinA to IncobotulinumtoxinA did not result in an inferior outcome for the treatment of facial dystonia and led to a cost-saving for the department.
Critique The study provided valuable insights into cost-saving without compromising efficacy. However, the retrospective design and small sample size, particularly in the HFS group, may limit the generalizability of the findings. The lack of randomization and potential bias due to the single-masked design are also limitations. Additionally, the BDS and Jankovic score may not be the best tools for monitoring AFR and HFS.
References:
[1] [1] Bladen JC, Favor M, Litwin A, Malhotra R. Switchover study of onabotulinumtoxinA to incobotulinumtoxinA for facial dystonia. Clin Exp Ophthalmol. 2020;48(9):1146-1151. doi:10.1111/ceo.13829
Efficacy and safety of a new Botulinum Toxin Type A free of complexing proteins in the treatment of blepharospasm
Design

Double-blind Phase III trial

N= 300
Objective To compare the efficacy and safety of NT 201 and BOTOX+ in patients suffering from blepharospasm
Study Groups

NT 201 (n= 148)

BOTOX+ (n= 152)
Inclusion Criteria Confirmed clinical diagnosis of blepharospasm requiring treatment by injection; exposure to at least two previous BOTOX+ injections resulting in a stable therapeutic response
Exclusion Criteria Atypical variant of blepharospasm, myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, significant neuromuscular disease, known alcoholism or drug abuse, severe or uncontrolled systemic diseases
Methods

Randomized, multicentre, double-blind study. Patients received a single injection of NT 201 or BOTOX+ (35 units per eye). Efficacy measured by change in Jankovic Rating Scale (JRS) sum score. Safety assessments included adverse event monitoring, laboratory tests, vital signs, ECGs.
Duration 16 weeks
Outcome Measures

Primary: Change in Jankovic Rating Scale (JRS) sum score

Secondary: Change in Blepharospasm Disability Index (BSDI), patient evaluation of global response
Baseline Characteristics Characteristic NT 201 (n= 148) BOTOX+ (n= 152)
Mean age, years 63 7.3 63 7.3
Female 72.7% 72.7%
Results Variable NT 201 (n= 148) BOTOX+ (n= 152) p-value
Change in JRS sum score at control visit -2.90 -2.67 <0.0001
Change in BSDI score at control visit -0.83 -0.82 0.91
Patient evaluation of global response at control visit 2.2 1.9 0.21
Adverse Events Ptosis (NT 201: 6.1%; BOTOX+: 4.5%), abnormal vision (NT 201: 1.4%; BOTOX+: 3.2%), back pain (NT 201: 1.4%; BOTOX+: 2.6%)
Study Author Conclusions NT 201 is non-inferior to BOTOX+ in treating blepharospasm, providing effective and long-lasting relief of symptoms with comparable safety profiles.
Critique The study's strengths include its double-blind design and large sample size, which enhance the reliability of the findings. However, the study's limitation is the potential variability in symptom assessment across different countries, which may affect the consistency of the results. Additionally, the study did not address long-term immunogenicity, which is a concern for chronic conditions requiring repeated treatments.

 

References:
[1] Roggenkämper P, Jost WH, Bihari K, Comes G, Grafe S; NT 201 Blepharospasm Study Team. Efficacy and safety of a new Botulinum Toxin Type A free of complexing proteins in the treatment of blepharospasm. J Neural Transm (Vienna). 2006;113(3):303-312. doi:10.1007/s00702-005-0323-3
A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia
Design

Double-blind, noninferiority trial

N= 463
Objective To demonstrate the noninferiority of NT 201 vs BOTOX in patients with cervical dystonia
Study Groups

NT 201 (n= 231)

BOTOX (n= 232)
Inclusion Criteria Patients diagnosed with cervical dystonia of the predominantly rotational form with a stable previous therapeutic response to BOTOX, TWSTRS Severity score ≥10, rotation score ≥2, and a rotation score higher than the score for laterocollis and retrocollis
Exclusion Criteria Patients with concomitant diseases that made an injection impossible
Methods

Randomized, double-blind, active-controlled, parallel-group trial. Patients received IM injections of 70 to 300 U of NT 201 or BOTOX. Primary efficacy variable was the change from baseline in TWSTRS Severity score at 28 ± 7 days post-injection. Secondary efficacy variables included TWSTRS Pain subscore, VAS Pain score, Global Response Scale score, responder rates, and investigator’s global assessment of efficacy. Safety evaluated based on adverse events, physical and neurologic examination, EKGs, and vital signs.
Duration 16 weeks
Outcome Measures

Primary: Change from baseline in TWSTRS Severity score at 28 ± 7 days post-injection

Secondary: TWSTRS Severity score at final visit, TWSTRS Pain subscore, VAS Pain score
Baseline Characteristics   NT 201 (n= 231) BOTOX (n= 232)
Total amount of study medication, U (mean ± SD) 140.4 ± 51.4 138.9 ± 46.8
Median TWSTRS Severity score at baseline 18 18
Results   NT 201 (n= 231) BOTOX (n= 232) p-Value
Change in TWSTRS Severity score at control visit -6.6 -6.4 <0.0001
TWSTRS Severity score at final visit (mean ± SD) -1.8 ± 3.4 -1.8 ± 3.8 0.7378
TWSTRS Pain subscore at control visit (mean ± SD) -0.4 ± 0.8 -0.6 ± 1.0 0.4082
VAS Pain at control visit (mean ± SD) -8.8 ± 18.5 -11.8 ± 19.4 0.2892
Adverse Events 28.1% of patients treated with NT 201 reported adverse events vs 24.1% with BOTOX. Dysphagia was the most frequently reported adverse event. Serious adverse events were observed in four patients of the NT 201 group and in five patients of the BOTOX group, none related to treatment
Study Author Conclusions

The study demonstrated noninferiority of NT 201 vs BOTOX in treating cervical dystonia. Complexing proteins in current BTX-A preparations are dispensable for clinical efficacy. Safety and tolerability profiles were similar for both treatments. NT 201 may lead to a reduced incidence of nonresponders after long-term treatment.
Critique

The study's strengths include its large sample size and rigorous double-blind design. However, the study's noninferiority design may not fully capture potential differences in efficacy or safety between NT 201 and BOTOX. Long-term effects and antibody development were not assessed, which are important considerations for chronic treatment.

 

References:
[1] Benecke R, Jost WH, Kanovsky P, Ruzicka E, Comes G, Grafe S. A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005;64(11):1949-1951. doi:10.1212/01.WNL.0000163767.99354.C3
A Prospective, Split-Face, Randomized, Double-Blind Study Comparing OnabotulinumtoxinA to IncobotulinumtoxinA for Upper Face Wrinkles
Design

Prospective, single-center, randomized, double-blind study

N= 45
Objective To evaluate the efficacy of onabotulinumtoxinA compared to incobotulinumtoxinA in reducing dynamic wrinkles in the upper face using a 1:1 dose ratio
Study Groups

OnabotulinumtoxinA (n= 45)

IncobotulinumtoxinA (n= 45)
Inclusion Criteria Men and women aged 18 years or older
Exclusion Criteria Previous treatment with a neuromodulator in the past 6 months, previous brow lift, currently pregnant or breastfeeding, history of neurologic disease or deficit, active facial skin infection, allergy to neuromodulators
Methods

Subjects were randomized to receive 22.5 units of onabotulinumtoxinA on one side of the face and 22.5 units of incobotulinumtoxinA on the other side. The study used a split-face design with a photographic upper face validated assessment scale for glabellar lines, crow’s feet, and forehead lines. Follow-up visits were at 3 days, 2 weeks, 3 months, and 4 months after treatment.
Duration 4 months
Outcome Measures Reduction in dynamic wrinkle score, reduction in static wrinkle score
Baseline Characteristics   All patients (n= 45)
Age, mean years 52.9
Female 41
Male 4
Results   OnabotulinumtoxinA IncobotulinumtoxinA p-Value
Combined dynamic wrinkle reduction at 3 days 1.11 1.02 0.010
Combined dynamic wrinkle reduction at 2 weeks 1.14 1.04 0.008
Combined dynamic wrinkle reduction at 3 months 0.60 0.52 0.013
Combined dynamic wrinkle reduction at 4 months 0.24 0.18 0.045
Adverse Events No adverse events were reported by any of the patients during the follow-up period
Study Author Conclusions

For identical dosage, both onabotulinumtoxinA and incobotulinumtoxinA are safe and effective in reducing dynamic wrinkles in the upper face; however, onabotulinumtoxinA had statistically greater efficacy at 3 days, 2 weeks, 3 months, and 4 months.
Critique

The study's strengths include its prospective, randomized, double-blind design and the use of a validated assessment scale. However, the split-face design may have limitations in terms of potential crossover effects, and the study's relatively small sample size may limit the generalizability of the findings.
References:
[1] 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
A Prospective Rater- and Subject-Blinded Study Comparing the Efficacy of IncobotulinumtoxinA and OnabotulinumtoxinA to Treat Crow's Feet: A Clinical Crossover Evaluation
Design Single-center, randomized, prospective, split-face, subject- and rater-blinded study with a clinical crossover evaluation N= 14
Objective To compare incobotulinumtoxinA with onabotulinumtoxinA in the treatment of crow’s feet
Study Groups

IncobotulinumtoxinA (n= 14)

OnabotulinumtoxinA (n= 14)
Inclusion Criteria Female subjects aged 40 to 65 years with symmetrical crow’s feet scoring 1 to 4 on the Merz 5-point scale at maximum contraction
Exclusion Criteria Marked facial asymmetry, intolerance to BoNT/A, previous treatment with biodegradable fillers in the face within the last 12 months, previous treatment with botulinum toxins, previous insertion of permanent materials in the face, surgery or scars on the face, history of facial nerve palsy
Methods Two consecutive treatment cycles, each of 3 months’ duration separated by 6 months. IncobotulinumtoxinA and onabotulinumtoxinA were administered to the lateral periorbital region of each eye using a 1:1 dose conversion ratio. The treatment applied to each side of the face was reversed in Cycle 2.
Duration Each treatment cycle lasted 3 months, with a 6-month washout period between cycles
Outcome Measures Primary: Severity of crow’s feet at rest and maximum contraction using the Merz 5-point scale
Baseline Characteristics  

IncobotulinumtoxinA (n= 14)

OnabotulinumtoxinA (n= 14)
Mean baseline score at rest 1.50 1.50
Mean baseline score at maximum contraction 2.21 2.21
Results  

IncobotulinumtoxinA (n= 14)

OnabotulinumtoxinA (n= 14)
1 month at rest 0.86 0.93
3 months at rest 1.50 1.71
1 month at maximum contraction 0.86 0.93
3 months at maximum contraction 1.50 1.71
Adverse Events A single adverse event (ecchymosis) was reported in Cycle 2 with incobotulinumtoxinA, which resolved quickly
Study Author Conclusions

IncobotulinumtoxinA and onabotulinumtoxinA (1:1 dose conversion ratio) were well tolerated, showing comparable efficacy and duration of treatment effect for crow’s feet.
Critique

The study's strengths include its split-face, crossover design which minimizes interindividual variation and bias. However, the small sample size limits the generalizability of the findings. Additionally, the study did not include a comparison with other BoNT/A products such as abobotulinumtoxinA, which could provide further insights into relative efficacy..

 

References:
[1] Muti G, Harrington L. A prospective rater- and subject-blinded study comparing the efficacy of incobotulinumtoxinA and onabotulinumtoxinA to treat crow's feet: a clinical crossover evaluation. Dermatol Surg. 2015;41 Suppl 1:S39-S46. doi:10.1097/DSS.0000000000000262
A randomised, double-blind comparison of 20 units of onabotulinumtoxinA with 30 units of incobotulinumtoxinA for glabellar lines
Design

Multicenter, randomised, double-blind study

N= 224
Objective To compare 20 units of onabotulinumtoxinA with 30 units of incobotulinumtoxinA in the treatment of glabellar lines
Study Groups

OnabotulinumtoxinA (n= 112)

IncobotulinumtoxinA (n= 112)
Inclusion Criteria Adults aged 18–65 years with moderate to severe glabellar lines at full contraction as assessed by the Facial Wrinkle Scale (FWS)
Exclusion Criteria Subjects unable to lessen glabellar line severity, had received botulinum toxin treatment within the last six months, previous surgery in the glabellar region, allergy to medication ingredients, disorders affecting muscular function, infection at injection site, facial asymmetry, ptosis, facial nerve palsy, bleeding disorders, use of aminoglycoside antibiotics, psychiatric problems
Methods Subjects received a single treatment with 20 units of onabotulinumtoxinA or 30 units of incobotulinumtoxinA. Vials were reconstituted with sterile 0.9% sodium chloride to achieve concentrations of 4 units/0.1 mL for onabotulinumtoxinA and 6 units/0.1 mL for incobotulinumtoxinA. Injectors administered 0.5 mL over 5 injection sites. Follow-up visits were conducted on days 28, 84, 98, and 112. Data was primarily presented as a graph.
Duration November 2010 to April 2011
Outcome Measures

Primary: Improvement of 1 point or more on the Facial Wrinkle Scale (FWS) at maximum contraction on day 28

Secondary: Injector and subject assessments of glabellar lines severity on days 84, 98, and 112
Baseline Characteristics   OnabotulinumtoxinA (n= 112) IncobotulinumtoxinA (n= 112)
Gender - Male 14 (12.5%) 10 (8.9%)
Gender - Female 98 (87.5%) 102 (91.1%)
Race - White 110 (98.2%) 109 (97.3%)
Race - Other 2 (1.8%) 3 (2.7%)
Age, years - Mean (SD) 45.0 (10.8) 45.4 (9.8)
Age, years - Median/range 46/20 – 65 45/20 – 65
Baseline FWS - Moderate 47.3% 45.5%
Baseline FWS - Severe 52.7% 54.5%
Results   OnabotulinumtoxinA (n= 112) IncobotulinumtoxinA (n= 112) p-value
Improvement of 1 point in FWS scores - Day 28 96% 95% 0.02
Improvement of 1 point in FWS scores - Day 84 Numerically greater Numerically smaller  
Improvement of 1 point in FWS scores - Day 98 Numerically greater Numerically smaller   
Improvement of 1 point in FWS scores - Day 112 Numerically greater Numerically smaller   
Adverse Events Most frequent adverse events: nasopharyngitis, oral herpes, back pain, influenza, spider vein. Mild pressure at injection site reported by 1 subject with onabotulinumtoxinA and 2 with incobotulinumtoxinA. No serious adverse events reported
Study Author Conclusions 20 units of onabotulinumtoxinA was as effective as 30 units of incobotulinumtoxinA at 28 days post injection, supporting the non-interchangeability of units and the absence of a fixed dose ratio in clinical practice.
Critique The study demonstrated equivalence at the primary endpoint but not at later time points, suggesting a trend favoring onabotulinumtoxinA. Limitations include the use of a 1-point change on the FWS as the primary endpoint and the potential impact of different product concentrations on outcomes. The study's findings are consistent with the non-interchangeability of biological products.
References:
[1] Moers-Carpi M, Dirschka T, Feller-Heppt G, et al. A randomised, double-blind comparison of 20 units of onabotulinumtoxinA with 30 units of incobotulinumtoxinA for glabellar lines. J Cosmet Laser Ther. 2012;14(6):296-303. doi:10.3109/14764172.2012.738913