Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action,Efficacy and Safety

Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.     

Clean intermittent catheterization rates after initial and subsequent treatments with onabotulinumtoxinA for non-neurogenic overactive bladder in real-world clinical settings

Objective: Previous randomized controlled trials have reported a 6.1–6.9% incidence of clean intermittent catheterization (CIC) following treatment with onabotulinumtoxinA in non-neurogenic overactive bladder (OAB) patients who were inadequately managed by ≥1 anticholinergic. A multi-center retrospective chart review assessed the real-world rate of voiding dysfunction requiring catheterization.

Methods: Patients received onabotulinumtoxinA 100?U (approved dose) administered by experienced injectors between January 2013 and June 2015. Patients using CIC or an indwelling catheter for ≥24?hours for voiding dysfunction prior to onabotulinumtoxinA injections were excluded. The primary outcome was post-treatment CIC (lasting >24?hours; per individual physician’s clinical judgment considering patient’s voiding symptoms, post-void residual [PVR] urine volumes and patient bother). Potential baseline predictors of CIC (history of pelvic prolapse, cystocele, diabetes, PVR urine volume and age) were assessed using multivariable logistic regression.

Results: Overall, 299 patients received their first treatment with onabotulinumtoxinA 100?U. Mean age was 66.4 years; 98.3% were female. The incidence of CIC was 2.7% in the total study population after the first treatment with onabotulinumtoxinA. The de novo CIC rate in treatments 2 and 3 combined was similarly low (3.2%). None of the evaluated baseline characteristics were significant predictors of CIC initiation due to the low CIC incidence.

Conclusions: This real-world study of non-neurogenic OAB patients treated with onabotulinumtoxinA suggests that the CIC rate is lower than the rates reported in previous studies. There were no significant correlations between baseline predictors and CIC initiation, although statistical significance may not have been reached because of the low incidence of CIC.     

Effects of intravesical onabotulinumtoxinA on bladder dysfunction and autonomic dysreflexia after spinal cord injury: role of nerve growth factor

Study Type – Aetiology (case control) Level of Evidence 3c What's known on the subject? and What does the study add? Neurogenic detrusor overactivity (NDO) and autonomic dysreflexia (AD) are common outcomes following spinal cord injury (SCI). In this study, we showed that onabotulinumtoxinA controlled NDO and AD in rats with T4‐SCI, and also provided a mechanism for the control of AS.

OBJECTIVE

• ? To assess the significance of onabotulinumtoxinA (onabotA) intravesical administration in blocking autonomic dysreflexia (AD) response induced by cystometrogram (CMG) after T4 spinal cord transection (SCT).

MATERIALS AND METHODS

• ? Female rats were stratified into three groups: a sham group; a SCT‐only group; and a SCT with onabotA treatment group. Each group was further subdivided into two subgroups: AD assessment, or nerve growth factor (NGF) assessment via enzyme‐linked immunosorbent assay (ELISA).
• ? Three weeks after T4‐SCT, all groups were assessed. Arterial pressure and heart rate were measured during and after CMG.
• ? NGF was also extracted from the bladder and the dorsal root ganglia (DRG) of the T4 root and quantified by ELISA. In the onabotA‐treated group, 48 h before assessment, onabotA (1 mL, 20 U/mL in saline) was given using a urethral tube and was left indwelling for 30 min.
• ? Univariate anova was used to analyse the data and statistical significance was set at P < 0.05.

RESULTS

• ? The maximum voiding pressure and the number of uninhibited contractions were significantly lower in the group treated with intravesical onabotA than in the SCT‐only group.
• ? Intravesical onabotA significantly blocked the dysreflexia response (high arterial pressure with bradycardia) induced by CMG after SCT.
• ? Intravesical onabotA also significantly lowered NGF concentrations in the bladder and the T4 DRG segment.

CONCLUSIONS

• ? The results of the present study showed that intravesical onabotA controls neurogenic detrusor overactivity and AD after SCT.
• ? The findings shed light on the potential benefits of intravesical onabotA treatment in patients with spinal cord injury, and also provide a novel mechanism for the control of AD via a minimally invasive treatment modality.