such an effective treatment in controlled clinical trials …
why did these patients discontinue [therapy]?”
Dr. Comella and Kailash Bhatia, MD, DM, Profes-
sor of Clinical Neurology at University College London,
conducted an international survey of self-identified pa-
tients with cervical dystonia to assess patients’ percep-
tions of their illness and its management. Of the more
than 900 patients who were receiving botulinum toxin,
56% were fairly or very satisfied with the treatment,
whereas 25% were fairly or very dissatisfied.
A survey by Sethi et al of 136 patients with cervical
dystonia found that 51% were very satisfied and 43%
were somewhat satisfied with botulinum toxin treat-
ment, but 45% would prefer a treatment cycle of 10
weeks or fewer. “The benefits of the injection wore out
before the next injection was permitted,” Dr. Comella
said. “That gave them two to three weeks of not doing
very well, which caused some dissatisfaction.”
Evidente et al studied the effect of flexible injection
intervals in the two pivotal trials of incobotulinum-
toxinA for blepharospasm and cervical dystonia. Af-
ter an initial double-blind, placebo-controlled period,
dosing intervals became flexible during a 68-week
open-label extension. During that time, patients could
request treatment after a six-week interval, and physi-
cians would administer the treatment at that time if
a patient’s dystonia was at a certain level of severity.
Among patients with blepharospasm, 26.5% of treat-
ments were administered at less than 10 weeks during
the flexible dosing period. Among patients with cervi-
cal dystonia, 29.5% of treatments were administered at
less than 10 weeks. Flexible dosing was well tolerated,
and no additional safety concerns were observed when
treatment was given sooner than 12 weeks after the
last injection, compared with treatment given after 12
or more weeks.
In limb dystonia, mostly occupational dystonias have
been studied, including writer’s cramp and musician’s
dystonia. The most frequent adverse event with botu-
linum toxin is weakness, which may lead to discon-
tinuation. In a 2007 study of abobotulinumtoxinA for
writer’s cramp that used continuation of treatment as
the primary outcome, 70% of patients who received
active treatment continued treatment, compared with
32% of patients in the placebo group. Hand weak-
ness occurred in about 90% of patients in the active
treatment group, however, compared with 25% of
patients in the placebo group, and 25% of patients in
the active treatment group discontinued because of
Neurologists adjust a patient’s injections based on the
patient’s response to the previous treatment, so treatment may become more beneficial as neurologists optimize the injection pattern and dosing.
Why Might Treatment Fail?
Injection of botulinum toxin into the wrong muscle
may be a common reason for lack of efficacy. Stress-induced exacerbation or inadequate dose may be other
reasons for treatment failure. Uncommon reasons for
lack of efficacy include change in dystonia and immunoresistance. In addition, patients may discontinue
treatment because of the expense or inconvenience,
Dr. Comella said.
Neurologists should help set realistic expectations for treatment. “We must manage patient expectations. It is not a cure. This may not restore you to
perfect movement,” Dr. Comella said. “Too often we
tell them how well they are going to do without giving
them a more realistic view.”
Neurologists need better long-term outcome data to
understand the effects of botulinum toxin in dystonia, and telemedicine may be an ideal way to assess
the treatment’s long-term efficacy, Dr. Comella said.
Remote evaluations could supplement in-person
evaluations and avoid reliance on patients’ retrospective reports.
An investigational formulation of botulinum toxin, daxibotulinumtoxinA, is being developed by Re-vance Pharmaceuticals. It contains a peptide excipient that is designed to produce a longer treatment
effect. A phase II open-label study is evaluating the
formulation in patients with cervical dystonia, said
Dr. Comella, who is one of the study investigators.
The reduced survival due to C9orf72
expansion primarily occurs in males
with spinal-onset disease. Median
survival among these patients may
be 2. 29 years.