Botulinum toxin therapy of cervical dystonia: comparing onabotulinumtoxinA (Botox®) and incobotulinumtoxinA (Xeomin®)

Several botulinum toxin (BT) drugs are licensed for the treatment of cervical dystonia (CD). We wanted to compare the efficacy and the potency labelling of incobotulinumtoxinA (Xeomin^®) and onabotulinumtoxinA (Botox^®) by analysing the duration of their therapeutic effect in a cross-over study. For this we studied 40 CD patients (26 females, 14 males, age at therapy onset 52.6 ± 12.0 years, duration of dystonia at therapy onset 10.0 ± 9.2 years, Tsui score 9.1 ± 3.9) who first received Botox^® and then Xeomin^® for at least 4 injection series each. BT doses were exchanged based on a 1:1 conversion ratio. Altogether 1,101 treatment cycles were evaluated. For each patient 27.5 ± 13.1 treatment cycles were recorded. Patients received 18.4 ± 12.4 treatment cycles with Botox^® and 9.2 ± 4.5 with Xeomin^®. The treatment duration (TD) throughout the treatment course was 11.3 ± 1.0 weeks (Botox^® 11.2 ± 1.1 weeks, Xeomin^® 11.4 ± 1.3 weeks). The interinjection interval (II) throughout the treatment course was 14.8 ± 1.9 weeks (Botox^® 14.7 ± 1.6 weeks, Xeomin^® 15.0 ± 2.2 weeks). The mean difference between Botox^® and Xeomin^® was 0.3 weeks for TD (two-sided 95 % confidence interval [?0.3; 0.9]) and 0.5 weeks for II (two-sided 95 % confidence intervals [?0.4; 1.4]). The confidence intervals of both parameters were within the predefined therapeutic equivalence range set to ±1.5 weeks, thus indicating similar efficacy of both BT drugs. Having based the exchange of Botox^® and Xeomin^® on a conversion factor of 1:1 our data confirm previous findings of an identical potency labelling of both products, thus allowing comparisons of efficacy, adverse effects and costs.     

Neuropathologic findings in a Guillain-Barré patient with strokes after IVIg therapy

Strokes have been rarely associated with immunoglobulin G (IVIg) therapy. A 70-year-old woman with stable polycythemia vera developed Guillain-Barré syndrome and received IVIg, 8 days following which she became comatose due to bilaterally symmetric cerebral infarcts. Autopsy showed intravascular aggregates of fibrin-IgG but also platelets and a necrotizing microangiopathy in the infarcts.     

Effective long-term treatment with incobotulinumtoxin (Xeomin®) without neutralizing antibody induction: a monocentric,cross-sectional study

Journal of Neurology - Among the spectrum of licensed botulinum neurotoxin preparations incobotulinumtoxin (incoBoNT/A; Xeomin®) is the only one which does not contain complex proteins....     

Sustained efficacy and safety of repeated incobotulinumtoxinA (Xeomin®) injections in blepharospasm

IncobotulinumtoxinA (Xeomin^®, NT 201) is a purified botulinum toxin type A free from accessory (complexing) proteins. Previous studies evaluated single sets of incobotulinumtoxinA injections for the treatment of blepharospasm. Individualized injection intervals and other potential determinants of efficacy and safety need to be evaluated in a prospective, longitudinal study. Subjects with blepharospasm who completed a ≤20 weeks double-blind, placebo-controlled main period entered a ≤69 weeks open-label extension period (OLEX) and received ≤5 additional incobotulinumtoxinA treatments at flexible doses (≤50 U per eye) and flexible injection intervals (minimum of 6 weeks). Outcome measures included Jankovic Rating Scale (JRS) (sumscore, severity subscore and frequency subscore), Blepharospasm Disability Index, and adverse events. All 102 subjects who completed the main period entered the OLEX; 82 subjects completed the study, 56 received the maximum five injections. From each injection visit to a control visit 6 weeks later, investigator-rated JRS sumscores and subscores, and patient-rated Blepharospasm Disability Index were significantly improved (p ≤ 0.001 for all). All scores were still significantly improved at trial termination compared with the first injection visit (p < 0.05 for all). The most frequently reported adverse events were eyelid ptosis (31.4 %) and dry eye symptoms (17.6 %). The injection interval had no impact on the incidence of adverse events (post hoc analysis). No subject developed neutralizing antibodies during the study. Repeated incobotulinumtoxinA injections, administered at flexible doses and injection intervals from 6 to 20 weeks according to subjects’ needs, provide sustained efficacy in the treatment of blepharospasm with no new or unexpected safety risks.     

A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin®) in cervical dystonia

IncobotulinumtoxinA (Xeomin^®, NT 201), a preparation without accessory (complexing) proteins, has shown comparable efficacy and safety to onabotulinumtoxinA in treating cervical dystonia (CD). This study evaluated the efficacy and safety of repeated incobotulinumtoxinA injections in subjects with CD. Following a ≤20-week placebo-controlled, randomized, double-blind, single-dose main period, subjects could enter a ≤68-week prospective, randomized, double-blind, repeated-dose, flexible-interval (minimum 6 weeks) extension period with 240 U or 120 U of incobotulinumtoxinA (≤5 injections). Outcome measures included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and adverse events (AEs). Of 219 subjects completing the main period, 214 were randomized in the extension period to receive incobotulinumtoxinA 240 U (n = 111) or 120 U (n = 103); 169 subjects completed the extension period, with 90 receiving five injection sessions. Both doses of incobotulinumtoxinA provided statistically significant and clinically relevant improvements in mean TWSTRS-Total, -Severity, -Disability, and -Pain scores, from each injection session to respective 4-week follow-up visits. The most frequently reported AE was dysphagia (240 U: 23.4 %; 120 U: 12.6 %), which did not result in any study withdrawals. There was no impact of injection interval on the incidence of AEs (post hoc analysis). A major limitation of this study was the fixed dose design requested by regulatory authorities, which does not reflect clinical practice. However, repeated incobotulinumtoxinA injections (240 or 120 U; flexible intervals) provided sustained efficacy and were well tolerated, with no unexpected safety risks following repeated injections. The incidence of AEs was similar in subjects requiring repeated injections at shorter intervals (≤12 weeks) compared with those treated using longer intervals (>12 weeks).     

Respiratory failure in a patient with antecedent poliomyelitis: Amyotrophic lateral sclerosis or post-polio syndrome?

We report a 69-year-old man who developed paralytic poliomyelitis in childhood and then decades later suffered from fatal respiratory failure. Six months before this event, he had progressive weight loss and shortness of breath. He had severe muscular atrophy of the entire right leg as a sequela of the paralytic poliomyelitis. He showed mild weakness of the facial muscle and tongue, dysarthria, and severe muscle atrophy from the neck to proximal upper extremities and trunk, but no obvious pyramidal signs. Electromyogram revealed neurogenic changes in the right leg, and in the paraspinal, sternocleidomastoid, and lingual muscles. There was a slight increase in central motor conduction time from the motor cortex to the lumbar anterior horn. Pulmonary function showed restrictive ventilation dysfunction, which was the eventual cause of death. Some neuropathological features were suggestive of amyotrophic lateral sclerosis (ALS), namely Bunina bodies. In patients with a history of paralytic poliomyelitis who present after a long stable period with advanced fatal respiratory failure, one may consider not only respiratory impairment from post-polio syndrome but also the onset of ALS.     

Onabotulinumtoxin type A (Botox®) versus Incobotulinumtoxin type A (Xeomin®) in the treatment of focal idiopathic palmar hyperhidrosis: results of a comparative double-blind clinical trial

Focal hyperhidrosis often has a substantial psychological and social impact on quality of life, since it interferes with daily activities. To date, for the treatment of focal hyperhidrosis, the botulinum toxin type A is an effective second line tool. The purpose of this study was to compare Onabotulinumtoxin A (Botox^®) and Incobotulinumtoxin A (Xeomin^®) administration in the treatment of palmar hyperhidrosis. In a double-blind clinical trial, 25 patients with moderate or severe palmar hyperhidrosis received in the same session intradermal injections of Onabotulinumtoxin A on one hand and Incobotulinumtoxin A on the other. Several measures of efficacy and safety were evaluated: disease severity improvement, sweat reduction, hand-grip strength decrease, pain/discomfort during the treatment, and patient’s global satisfaction. All patients were responsive to the treatments (HDSS at T4 vs HDDs at T0; p < 0.0001), and no significant difference between Onabotulinumtoxin A and Incobotulinumtoxin A in terms of anhidrotic effect (Minor’s test at T4; p = 0.51), long-term efficacy (Minor’s test at T12; p = 0.76), (Minor’s test at T24; p = 0.58), subjective pain related to the injections (p = 0.88), muscle strength reduction after treatment (p = 0.56), and global satisfaction with the treatment (p = 0.26). Onabotulinum toxin A and Incobotulinumtoxin A seem to be comparable in terms of anhidrotic effect (short-term results), duration of benefits (long-term efficacy), muscle strength reduction (safety), pain related to injections (tolerability), and treatment satisfaction expressed by patients.     

Secondary failure after ten years of pallidal neurostimulation in a patient with advanced Parkinson’s disease

Deep-brain stimulation of the subthalamic nucleus and internal globus pallidus are both surgical options in advanced Parkinson’s disease. The best target is still debated with data suggesting better motor outcome in subthalamic stimulation but higher rates of psychiatric problems. Failure of pallidal stimulation within the first 2 years has been described. Here, we report a patient with good response to pallidal neurostimulation who developed a secondary failure after 10 years of treatment which was successfully reversed by reimplanting the electrodes into the subthalamic nucleus. This case suggests that a controlled comparison of treatment efficacy of pallidal and subthalamic neurostimulation may require a very long follow-up period to yield reliable results.     

Biological activity of two botulinum toxin type A complexes (Dysport® and Botox®) in volunteers

Journal of Neurology -     

Biological activity of two botulinum toxin type A complexes (Dysport® and Botox®) in volunteers

Despite extensive clinical experience and published data regarding botulinum toxin, questions remain about the clinical substitution of one botulinum toxin formulation for another. In the case of Dysport and Botox, dose-equivalence ratios ranging from 1:1 to 6:1 (Dysport:Botox) have been advocated. This dose-ranging, electroneurographic study investigated the dose equivalence, diffusion characteristics (spread) and safety of these two type-A toxins in 79 volunteers. Dysport and Botox caused significant and similar reductions in compound muscle action potential (CMAP) amplitude in the target muscle (extensor digitorum brevis, EDB) 2 weeks after injection, with effects persisting to the 12-week timepoint. For both products, the reduction in amplitude was increased with increasing doses and with increasing concentration. The effects of toxin on neighbouring muscles were much smaller and of a shorter duration than those on the target muscle, implying a modest spread of toxin. Unlike the target muscle, the effects were greater with the higher volume, suggesting this volume led to greater diffusion from the EDB. No adverse events were reported. Statistical modelling with CMAP amplitude data from the target muscle gave a bioequivalence of 1.57 units of Dysport:1 unit of Botox (95 % CI: 0.77-3.20 units). The data indicate that a dose-equivalence ratio of 3:1 was within the statistical error limits, but ratios over 3:1 are too high.     

Guillain-Barré syndrome in a patient with primary sicca syndrome

At the age of 23 the patient showed the first signs of dryness syndrome. Those symptoms developed progressively and during a few years primary Sj?gren syndrome was noted. In the 37th year of life suddenly the patient developed very severe Gullian-Barré syndrome with involvement of the peripheral and central nervous system and with a considerable autonomic component. After treatment the patient improved, however mild symptoms of central and peripheral nervous system destruction remained. Those symptoms are still present and the patient is under the care of the Neurology and Rheumatology Clinic.     

Hypoglycemia-induced hemichorea in a patient with Fahr’s syndrome

Non-ketotic hyperglycemia may be a cause of hemiballism-hemichorea. We present an elderly female type II diabetic patient with right-sided hemiballism-hemichorea of acute onset during hypoglycemia following insulin overtreatment of non-ketotic hyperglycemia. Brain computerized tomography and magnetic resonance imaging scans revealed characteristic hyperdensity and T1 hyperintensity, respectively, in the left basal ganglia, in addition to pallido-dentate calcifications, suggestive of Fahr’s syndrome. Although extremely rare, hypoglycemia may be a cause of hemiballism-hemichorea especially in the presence of predisposing factors such as previous hyperglycemic episodes and Fahr’s syndrome.