Effective converting ratio when switching
between Ona-botulinumtoxin-A and Abo-botulinumtoxin-A in cervical dystonia.
A patient assessment cross over study
Ninel Nazarian*, and Erik Hvid Danielsen
Department of Neurology, Consultant Neurologist, Aarhus University Hospital, Nörrebrogade 44 DK-8000 Aarhus C, Denmark
Submission: May 01, 2019; Published: November 25, 2019
*Corresponding author: Ninel Nazarian, Department of Neurology, Consultant Neurologist, Aarhus University Hospital, Nörrebrogade 44 DK-8000 Aarhus C, Denmark
How to cite this article: Ninel Nazarian, Erik Hvid Danielsen. Effective Converting Ratio when Switching between on a-Botulinum toxin-a and Abo-
Botulinumtoxin-a in Cervical Dystonia a Patient Assessment Cross over Study. Open Access J Neurol Neurosurg. 2019; 12(2): 555832.
Keywords: Abo-botulinumtoxin-A Ona-botulinumtoxin-A Cervical dystonia Effective conversion ratio VAS-score Follow-up Retrospective study
In the 1950s it was hypothesized that Botulinum Neurotoxins (BoNT-A’s) could be used to reduce activity in muscle disorders . Botulinum neurotoxin is made of a gram-positive anaerobic bacterial exotoxin-
clostridium botulinum . When injected in the skeletal muscle, the botulinum toxin inhibits vesicular neurotransmitter (acetylcholine) release at the neuromuscular junction at the presynaptic membrane and a local chemo-denervation appears . Thereby the toxin can reduce muscular contraction, which is the desire to reduce overactive muscle activity [3-5]. The medical therapies for dystonia are effective, and studies have shown that botulinum toxin is the most effective treatment for cervical dystonia . The evidence from several Class I and Class II studies has led to a level A recommendation for use of BoNT-A for treating focal dystonia such as cervical dystonia, hemifacial spasm and blepharospasm . Three main BoNT-A products are available on the market today: Ona-botulinumtoxin-A (Botox®), Abo-botulinumtoxin-A (Dysport®) and Inco-botulinumtoxin (Xeomin®). Due to different production methods, the biological nature of the three BoNT-A’s are different (e.g. the protein load, formulation, pH, dose and immunogenicity). Moreover, the BoNT-A’s are not interchangeable on an equivalent-dose basis [1, 7].
The goal of this study was to find the optimal conversion ratio for patients with cervical dystonia when switching treatment between Abo-botulinumtoxin-A and Ona-botulinumtoxin-Awhile obtaining a stable satisfying symptom improvement based on a subjective patient assessment. There is heterogeneity in treatment strategies and on how doses and the effect of BoNT-As are reported until now. This study represents a retrospective (follow-up), cross-over study (each patient acts as his/her own control). Effect of treatment was based on individual patient assessment. Individual based conversion rates were calculated using the optimal treatment dose for Abo-botulinumtoxin-A and Ona-botulinumtoxin-A. Due to the length of the present study with a follow-up time from 1991 to end 2014, it was possible to find stable toxin doses where each patient felt the best effect (min. 90%, VAS-score).
The clinical data was sampled from the patients’ medical records. Dystonic muscles and injection sites were identified by using electromyography (EMG). The neurologist determined the toxin doses based on each patient´s disease condition and the dystonic muscles activity (EMG). Each treatment (dosing) pr. clinical visit was individualized. At each consultation the neurologist reported the data (doses of toxin and the patient assessed effect and side effects) in the internal IT-system (Danish electronical patient journal) and also used standard sketches of the face/neck-regions to note which muscles have been injected
Ona-botulinumtoxin-A was diluted with saline to a concentration of 40U/ml. Abo-botulinumtoxin-A was dilutedwith saline to a concentration of 200 U/ml. For cervical dystonia
the injection sites were between 2-8 sites. The injection doses
in the specific muscles pr. patient and the total botulinum toxin
doses pr. consultation were registered.
The patients received treatment with BoNT-A´s every 3rd
month at the neurological movement disorder clinic by an
experienced neurologist. The subjective assessment of maximal
treatment effect on dystonia symptoms between each treatment
visits, were evaluated at each visit by the patient on a horizontal
100-mm Visual Analogue Scale (VAS) ; where the left end point
indicated 0% treatment effect (no change in dystonia symptoms
and no effect of the botulinum toxin) and the right end point
indicated a total 100% treatment effect (indicate no dystonia
symptoms and a maximal effect of botulinum toxin) between
In this study, data was only obtained from patients with a
stable idiopathic cervical dystonia, and no change in relevant
medical treatment over the data recording period. (Patient
study entry, Table 1). The mean individual dose of Onabotulinumtoxin-
A was obtained from 4 continuous consultations
from each patient with a symptom relief of >90%. The treatment
was then changed to Abo-botulinumtoxin-A after filtration
to maximal effect and the mean individual dose of this toxin
was obtained in the same manner as Ona-botulinumtoxin-A.
The conversion ratio of Ona- & Abo-botulinumtoxin-A could
then be calculated for each individual by dividing the mean
individual Ona-botulinumtoxin-A dose with the mean Abobotulinumtoxin-
A dose. The final average conversion ratio (Ona-
BoNT-A: Abo-BoNT-A) in the study was found by using all the
individual conversion ratio data from the 48 patients (Figure 1).
625 out-patients in total were registered at the movement
disorder clinic and received treatments with botulinum toxins.
Of these, 48 patients with cervical dystonia patients met the
inclusion criteria (Figure 2).
Cervical treatment was determined by the level of dystonia
and ranged between 25- 200 units (Ona-botulinumtoxin-A)
and 125- 775 units (Abo-botulinumtoxin-A) pr. clinical visit.
More females had dystonia and most of the patients’ ages
were between middle 50s to middle 70s (Table 2). All data wascollected in a period of 25 years from the movement disorder
clinic. The VAS-outcome for each patient was minimum 90%.
This retrospective data formed a cross-over design as each
patient acted as his/her own control. Therefore, patients with
confounders such as smoking, obesity etc. and comorbidities
such as heart and lung diseases were not excluded, due to the
cross over design. The average treatment time for patients with
cervical dystonia receiving Ona-botulinumtoxin-A and Abobotulinumtoxin-
A was 15,8±4,6 years. This average treatment
time is the total period before and after switching botulinum
toxin-A. 2546 injection series (total) were analyzed. Doses were
126 ± 38,8 IE-U for Ona-botulinumtoxin-A and 381,6 ± 151,1
IE-U for Abo-botulinumtoxin-A (Table 3). The mean conversion
ratio for cervical dystonia was 1: 2.56. (Table 4).
We are reporting 55 patients who converted treatment
between Abo- and Ona-botulinumtoxin-A. All data wascollected in a period of 25 years from the movement disorder
clinic. Patients have been stabilized with the Ona- or Abobotulinumtoxin-
A treatment for at least a year before crossing
over to treatment with the other toxin. Due to the long followup
and moderate amount of data, we were able to find the
average conversion ratio based on each patient´s subjective
assessment. Former reports show no statistically significant
difference on duration of the effect or adverse effects between
Ona-botulinumtoxin-A and Abo-botulinumtoxin-A . Data in
these topics were excluded and not evaluated here. Treatment
effect of Ona-botulinumtoxin-A and Abo-botulinumtoxin-A was
in this study assessed by the treated patients. Due to the routine
feedback from each of the treated patients over several years
it was possible to achieve regular measurement of treatment
effect from a subjective patient perspective without extra time
for objective observations and evaluation in between toxin
treatment sessions. The conversion ratio between the toxins
(Ona-BoNT´s and Abo-BonT´s) using a patient-based assessment
has in the present study shown to be equal to the study where
they were using multicenter double-blind randomized trials .
Due to risk of different treatment techniques, toxin diffusion
and especially individual variation in differentiating on relevant
pain, a 90% margin was chosen as cut off for registration of
One unit of Ona-botulinumtoxin-A is not bioequivalent to one
unit of Abo-botulinumtoxin-A. The ratio- Ona-botulinumtoxin-A:
Abo-botulinumtoxin-A varies between 1:3 and 1:6 . An
earlier double-blinded study showed that the conversion ratio
of Ona-botulinumtoxin-A and Abo-botulinumtoxin-A was 1:3
. Abo-botulinumtoxin-A has been shown to have a doserelated
significant longer duration of the effect rather than Onabotulinumtoxin-
A, with a ratio 1:4 (Ona-botulinumtoxin-A: Abobotulinumtoxin-
A, p-value= 0,02) . Similar to former reports
12, this report have shown that the effect on dystonia, stabilizes
after a period of treatments when changing between different
toxin doses. In the present study the toxin doses were stabilized
when the patients felt an effect of at least 90% measured on a
VAS-score (0-100%) minimum at 4 continuous consultations.
Experimental results have shown that Abo-botulinumtoxin-A
diffuses faster than Ona-botulinumtoxin-A which was explained
by Abo-botulinumtoxin-A´s lighter molecular weight; Abobotulinumtoxin-
A 3-400 kDa vs. Ona-botulinumtoxin-A 900kDa
, and therefore the side effects in Abo-botulinumtoxin-A
compared to Ona-botulinumtoxin-A was assumed due to a higher
diffusion rate [17-19]. Other studies stated that botulinum
toxin products dissociate under physiological conditions, and
therefore the time of diffusion is not related to the toxin size .
In a study using Abo- and Ona-botulinumtoxin-A in the same
patient with palmar hyperhidrosis, the patient was treated with
Ona-botulinumtoxin-A in one palm, and Abo-botulinumtoxin-A
in the other palm at the same session for 8 months. The patientswere their own control- like in the present study. The conclusion
of that study was that the efficacy and safety of treating with
Ona-botulinumtoxin-A and Abo-botulinumtoxin-A was by using
the toxins in the conversion ratio of 1: 2.5  which is similar to
our conclusion. It has also been shown that conversion ratios of
1:3 or lower could be appropriate for the treatment of spasticity,
cervical dystonia, hemifacial spasm, and blepharospasm 22.
In the present study we found the conversion ratio of cervical
dystonia to be 1:2, 56 which is similar to the former findings [21,
The repeated administration and documentation of the
usage of toxin doses (every 3rd month) at the movement
disorder clinic reduced the information and selection bias.
Due to the long follow-up period with a positive outcome and
rare expected side effects, it was found to be effective to use
a conversion ratio of 1: 2,56 (Ona-BoNT-A : Abo-BoNT-A) for
botulinum toxin-A. The present study did not exclude any
patients if they had confounders or comorbidities in behalf of
that each patient was his/her own control in this cross-over
design. The study design intended to prevent informational bias
when evaluating the effect shortly after the toxin injections. To
prevent selection and treatment variation bias the use of data
was from patients who have been stabilized first with either
Ona- or Abo-botulinumtoxin-A treatment for at least a year
before crossing over to treatment with the other BoNT-A.
Considering the positive treatment effect, and the long followup
period, we concluded that it is safe and clinically useful to use
a conversion ratio at 1: 2,56 based on a patient assessment when
changing treatment in between Ona- and Abo-botulinumtoxin-A
for cervical dystonia. We consider the conversion ratios in our
study applicable in other settings as well thus the effect of the
botulinum toxin treatments was evaluated on a VAS-score (each
patient is his/her own control) in this long follow-up study on