Switch from onabotulinumtoxin A to abobotulinumtoxin A
with the first injected product. However, circumstances
such as administrative changes can restrict the choices
available to the clinician.
There is little information on the efficacy and safety
of continued treatment when children are switched
from one product to another. We report here the results
of a single-centre retrospective study of children who
switched from onabotulinumtoxin-A (OnaBoNT-A) to
abobotulinumtoxin-A (AboBoNT-A) due to changes in
administrative processes and reimbursement policies.
The main aims of this analysis were to explore whether
switching from OnaBoNT-A to AboBoNT-A is safe
and well-tolerated and whether therapeutic efficacy is
maintained from one product to another.
METHODS
This was a retrospective, single centre, observational study
conducted at the Kocaeli University (KOU) Department of
Physical Medicine and Rehabilitation (PMR), which is active
in clinical research and routinely collects detailed clinical as-
sessment data. The study was approved by the ethics committee
of KOU School of Medicine and Research-Education Hospital
(project number KU GOAEK 2017/90).
Patients and treatment setting
The only inclusion criteria for this retrospective analysis were
a diagnosis of CP and lower limb hypertonia treated in KOU
Department of PMR from 2007 to 2017. Children had to have
had at least 2 consecutive cycles of BoNT-A treatment; one
cycle with OnaBoNT-A and one with AboBoNT-A. Since the
units of the toxins are specific to their preparation and not in-
terchangeable, no conversion ratio or fixed dose was used; all
patients were individually evaluated.
All BoNT-A injections were routinely administered under
guidance (electrical stimulation with or without ultrasound);
the use of sedation/anaesthesia depended on the individual
patient. Injection parameters were individualized according to
the goals of treatment, motor severity, accompanying distur-
bances, age and weight of the patient, body region, the size of
the targeted muscle(s), neuro-muscular junction distribution for
the muscle(s) and previous experience with BoNT-A. Goals of
treatment varied widely in line with the heterogeneity of the
clinic population, and varied from improvement in running (e.g.
to play football in children with Gross Motor Function Clas-
sification System (GMFCS) level I) to ease of nappy change.
All children were managed by a multidisciplinary team
consisting of PMR physicians, physical therapists, occupa-
tional therapists and students, special education specialists,
recreational sports specialists, and orthotists. Following each
BoNT- A injection, the children entered a 3-week intensive
rehabilitation programme (half day or full day), which can
be extended for a further 3 weeks if robotic rehabilitation is
employed. The programme typically started 7–10 days after
BoNT-A injection, and was designed by the senior PMR phy-
sician according to individualized therapeutic goals. Available
adjunctive treatments included serial casting, orthotics, physical
therapy, occupational therapy, cognitive rehabilitation, special
educational programmes, non-invasive brain stimulation with
transcranial direct current, neurofeedback, biofeedback, whole-
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body vibration, Biodex balance training, electrical stimulation
and other physical therapy modalities, activity-based models,
including functional ambulation training, constraint-induced
therapy, bilateral intensive therapy, hippotherapy, music t herapy
by singing or playing percussive instruments or moving and
dancing to music, virtual reality and robotic rehabilitation.
Assessments
As per routine practice, comprehensive clinical assessments were
performed at the start of each treatment cycle (baseline) with
a follow-up at week 4–6 post-injection. Routine assessments
include the Modified Ashworth Scale (MAS) and Tardieu Scale
(TS). Although not all goals were related to gait, we routinely
assess gait function using the Observational Gait Scale (OGS) for
children with GMFCS levels I–IV. At each visit parents and care-
givers are questioned regarding the occurrence of adverse events
(AEs) and their temporal relationship to the BoNT-A injection.
The primary objective of the analysis was to document the
safety of switching from OnaBoNT-A to AboBoNT-A. Infor-
mation on AEs and their relation to BoNT-A treatment was
collected for the final OnaBoNT-A treatment cycle prior to the
switch, and for the first AboBoNT-A treatment cycle following
the switch. Data were collected until the following treatment
cycle or for a post-treatment period of 6 months after the switch.
It was also assessed whether therapeutic efficacy was maintained
with the product switch, where therapeutic effects on muscle
tone and spasticity were evaluated using the MAS and TS,
respectively, and gait function was assessed using the OGS.
Analysis
All statistical analyses were limited to the final OnaBoNT-A
treatment cycle prior to the switch, and the first AboBoNT-A
treatment cycle following the switch. The distribution of treat-
ment emergent adverse events (TEAEs) and treatment-related
AEs across the OnaBoNT-A and AboBoNT-A treatment cycles
were compared using McNemar’s test. Efficacy outcomes at
4–6 weeks post-injection were compared with the baseline of
each treatment cycle. The mean change from baseline to week
4–6 in derived MAS score; mean change in angle of arrest at
slow speed (XV1), angle of catch at fast speed (XV3), spasti-
city angle (X), and spasticity grade (Y) of TS from baseline to
post-treatment week 4–6 for ankle plantar flexor, hamstring, hip
adductor muscle groups; and mean change in OGS score for
OnaBoNT-A and AboBoNT-A treatment cycles were compared
using Students’ t-test for paired data.
RESULTS
Retrospective analysis of case records identified 118
children with CP who fulfilled the inclusion criteria
for this study. Baseline characteristics and type of
adjunctive therapy given are provided in Table I. Over
half (53.4%) were independent walkers and, of these,
30% used walking aids. Children had received a mean
of 3.7 (SD 3.2) treatment cycles with OnaBoNT-A
before switching to AboBoNT-A. Mean total doses
were 227.4 U (standard deviation (SD) 63.1) (13.7 U/
kg (SD 5.0)) for OnaBoNT-A and 708 U (SD 194.1)
(36.3 U/kg (SD 13.3)) for AboBoNT-A. Table II
J Rehabil Med 51, 2019