Budget impact analysis of botulinum toxin A therapy for upper limb spasticity in the United Kingdom.

BACKGROUND: Botulinum toxin A (BoNT-A) is an effective treatment for patients with upper limb spasticity (ULS), which is a debilitating feature of upper motor neuron lesions. BoNT-A preparations available in the UK are associated with different costs. METHODS: We developed a budget impact model to assess the effect of changing market shares of different BoNT-A formulations - abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA - and best supportive care, from the UK payer perspective, over a 5-year time horizon. Epidemiological and resource use data were derived from published literature and clinical expert opinion. One-way sensitivity analyses were performed to determine parameters most influential on budget impact. RESULTS: Base-case assumptions showed that an increased uptake of abobotulinumtoxinA resulted in a 5-year savings of £6,283,829. Treatment with BoNT-A costs less than best supportive care per patient per year, although treating a patient with onabotulinumtoxinA (£20,861) and incobotulinumtoxinA (£20,717) cost more per patient annually than with abobotulinumtoxinA (£19,800). Sensitivity analyses showed that the most influential parameters on budget were percentage of cerebral palsy and stroke patients developing ULS, and the prevalence of stroke. CONCLUSION: Study findings suggest that increased use of abobotulinumtoxinA for ULS in the UK could potentially reduce total ULS cost for the health system and society.

The pharmacological management of post-stroke muscle spasticity.

Muscle hypertonia following upper motor neurone lesions (referred to here as 'spasticity') is a common problem in patients with neurological disease, and its management is one of the major challenges in clinical practice. Understanding the pathogenesis and clinical course of spasticity is essential for the effective management of this condition. The hypertonia initially results from increased excitability of the alpha motor neurones due to an imbalance between the excitatory and inhibitory influences of the vestibulospinal and reticulospinal tracts. This is the 'neural component' of muscle hypertonia. However, usually within 3-4 weeks, changes in the structure and mechanical properties of the paralysed muscles and the effect of thixotropy also contribute to the hypertonia. The selection of the optimal treatment option is often influenced by whether the neural or the non-neural component is more pronounced. Muscle spasticity often interferes with motor function or causes distressing symptoms, such as painful muscle spasms. If untreated, spasticity may also lead to soft tissue shortening (fixed contractures). However, spasticity can also be beneficial to patients. For example, despite severe leg muscle weakness, most hemiplegic patients are able to walk because the spasticity of the extensor muscles braces the lower limb in a rigid pillar. Other reported benefits of spasticity include the maintenance of muscle bulk and bone mineral density and possibly a reduced risk of lower limb deep vein thrombosis. Several factors, such as skin pressure sores, faecal impaction, urinary tract infections and stones in the urinary bladder, can aggravate muscle spasticity. These factors should always be looked for as their adequate treatment is often sufficient to reduce muscle tone without the need for specific antispasticity medication. Therefore, a careful evaluation of the patient's symptoms and their impact on function, and the setting of clear and realistic therapy goals are important prerequisites to treatment. The best treatment outcomes are usually achieved when pharmacological and non-pharmacological treatment modalities are used in tandem. Different drugs are available for the management of spasticity, including oral muscle relaxants, anticonvulsant drugs, intrathecal baclofen, cannabis extract, phenol and alcohol (for peripheral nerve blocks) and botulinum toxin injections. Similarly, there is a range of non-pharmacological methods of treatment, e.g. regular muscle stretching, the use of splints and orthoses, electrical stimulation, etc. Although these are not discussed here, this should not detract from the importance of combining them with antispasticity drugs in order to maximize the clinical benefit of treatment.

The effect of total cumulative dose, number of treatment cycles, interval between injections, and length of treatment on the frequency of occurrence of antibodies to botulinum toxin type A in the treatment of muscle spasticity.

A large cumulative dose of botulinum toxin type A (BoNT-A), frequent injections, a short interval between treatment cycles, and a long duration of treatment have all been suggested, but not confirmed, to be associated with a high incidence of neutralizing antibodies to the neurotoxin. The aim of this study was to investigate whether these variables predispose to BoNT-A neutralizing antibody formation. A mouse protection (neutralization) bioassay was used for the detection of BoNT-A antibodies in 17 patients who received large doses of BoNT-A, over at least 10 consecutive treatment cycles or for 5 years or more. BoNT-A antibodies were not detected in any of the study patients. The study findings did not confirm an association between the above-mentioned variables and BoNT-A antibody formation.

Spasticity or reversible muscle hypertonia?

BACKGROUND AND OBJECTIVE: The increase in resistance to passive muscle stretch in a paretic limb due to an upper motor neurone lesion is often referred to as muscle spasticity. However, this terminology is inaccurate and does not take into account the complex pathogenesis of the condition or describe the factors that contribute to the clinically observed changes in muscle tone. In this report we propose an alternative terminology and explain the reasons for doing so.