Abstract
Response:
We thank Professor J.M. Zakrzewska (1) for the thoughtful comments on our study. Recent published studies support an effect of onabotulinumtoxinA on pain (2–4). Until recently, a large number of open-label trials and case reports have evaluated the therapeutic effect of onabotulinumtoxinA on the management of trigeminal neuralgia (TN), and all authors reported positive findings (5). To further advance these findings, we conducted this randomized, double-blind, placebo-controlled trial (6).
It is worth noting that the onabotulinumtoxinA used in this trial was obtained from Lanzhou Biologic Products Institute (China), not Botox® (Allergan, Inc). Because doses of different formulations of onabotulinumtoxinA are not interchangeable, it is not clear whether the same dose of other formulates of onabotulinumtoxinA can exert the same effects.
TN is defined as severe, stabbing recurrent episodes of pain. Patients often reported that both pain intensity and attack frequency are unbearable and have a negative impact on their well-being. We also found that pain intensity and attack frequency were synchronous changes in a previous study (7), so we defined pain intensity and attack frequency as the primary endpoints. The mean score in this study was generated from the daily diaries over a week; this is a universal method in pain research. “Patient global impression of change” was taken at the endpoint, which evaluated the patient’s overall change since baseline. Scientific research should be subject to the principle of a single variable. For the purpose of minimizing the influence of the experimental results, the analgesic medicines used to control pain were kept unchanged during the course of the study. Carbamazepine is established as effective and oxcarbazepine is probably effective for controlling pain in patients with TN. WP Cheshire Jr. also suggested that gabapentin can be effective as a first- or second-line treatment of TN (8).
Twenty-three screened patients were excluded for failing to meet study criteria, and two were excluded for withdrawing consent. We have treated 15 patients with botulinum toxin type A (BTX-A) in a previous study (5). According to this data, we expected that the mean decrease of visual analogue scale scores would be 30% in the placebo group. Then, this sample size would provide a >75% power at a two-sided significance level of 0.05. The randomization sequence of this study was generated using SAS programming language. We designed the study in such a way that the person who did the randomization and prepared the syringes did not take part in the injection and measurement procedures. Physicians performing the injections and the investigators were both blinded during the entire study. In order to reduce the risk of unblinding, the physicians and investigators were specifically instructed not to make any comments to patients regarding their impression of any treatment outcome. BTX-A was applied at 15 points in each patient regardless of whether one or more branches of the trigeminal nerve were involved, and the injections were administered using two syringes. All the patients attended all the follow-up visits in this trial.
TN is indeed a long-term condition, but the results of this trial did not mean that the efficacy of BTX-A lasted only 12 weeks. In the previous study, we found that pain remained absent for at least 15 months after BTX-A treatment in one patient (5). In addition, a trial is going on to evaluate the long-term efficacy of BTX-A for the treatment of TN in our hospital. In conclusion, based on the scientific data, we do not quite agree with the comments of J.M. Zakrzewska (1). We still conclude that BTX-A may be an efficient strategy for TN treatment.