Axonics sacral neuromodulation system for treating refractory overactive bladder

A new rechargeable sacral neuromodulation (SNM) system, InterStim Micro (Medtronic), was launched in the UK when Axonics SNM system was being assessed. The clinical experts explained that InterStim Micro was not yet widely used in the NHS so had not been accepted as standard NHS practice. The external assessment centre (EAC) reported that there was currently no published evidence on InterStim Micro for treating symptoms of overactive bladder. The committee concluded that the appropriate comparator for the Axonics SNM system in this evaluation remained the non-rechargeable SNM system.

The committee noted the non-comparative evidence from 2 studies (ARTISAN‑SNM and RELAX‑OAB) and testimony from a patient survey. Some patients described the technology as 'completely life changing', others felt in control of their condition. The clinical experts said that Axonics SNM system improves symptoms and quality of life. They noted that the test phase programming for both devices was different and that Axonics SNM system had 2 programs available during the test period. The Axonics SNM system permanent implant has 1 program, whereas the standard non-rechargeable SNM system has 4 default programs that a patient can switch across remotely. All programs for both Axonics SNM system and the standard non-rechargeable SNM system can be optimised for individual patients. The permanent implantation procedure is similar for both devices. The committee concluded that Axonics improves symptoms of overactive bladder and quality of life.

The committee noted that there was a lack of long-term follow-up data from the existing studies that validated the company's claim of extended battery life in real-world use. The technical expert explained that battery longevity depends on the recharge interval, charging regime and discharge profile. Newcastle EAC did an assessment of accelerated battery bench testing data submitted by the company. Based on this and expert advice, the committee concluded that it was plausible that the Axonics SNM battery would last 15 years for a person who needs typical stimulus (2.1 milliampere) to manage their symptoms. No data on battery failure were submitted and the committee was also advised that the recharge interval depended on stimulation parameters. Also, some devices may fail within the 15‑year life span if stimulus current of up to 4 milliampere is needed to manage symptoms. Mild cases of lead migration were noted as a possible cause of changes in stimulus current. The committee further considered that evidence from RELAX‑OAB showed that stimulation amplitude increased up to 3 months after the device was implanted. But, in the longer term, once the lead settles in the body, amplitude may stabilise or decrease. The committee concluded that even though evidence on battery life was limited, it was plausible that the battery would last at least 6 years and possibly beyond 15 years.

The clinical experts explained that it was difficult to predict what proportion of people had symptoms that would stop responding over the 15‑year life span of the Axonics SNM system. They stated that all treatments for overactive bladder are associated with some level of decline in response. This could be because of the person's lifestyle, loss of efficacy, break in circuit or anticipated changes in the stimulation delivered. Clinical experts advised that a therapy break may be recommended to assess if people should continue to use SNM therapy (rechargeable or non-rechargeable). The committee noted that long-term therapy breaks (for desensitisation or pregnancy) may reduce the rechargeable battery life, but evidence of this was not available. The committee concluded that although desensitisation may occur, this is unlikely to be different with Axonics SNM system than with the non-rechargeable system.

There was no evidence on adverse events beyond 2 years. The most common minor device-related adverse events related to discomfort associated with stimulation. Clinical experts agreed that discomfort with stimulation can usually be corrected with reprogramming. The committee concluded that no serious adverse events had been reported with Axonics SNM system.

The clinical experts explained that Axonics SNM system is usually used in their practice as a third-line therapy after conservative treatment and treatment with medicine have not worked, which is in line with NICE's guidelines on urinary incontinence and pelvic organ prolapse and lower urinary tract symptoms. They explained that SNM is normally expected to be the only therapy needed to improve symptoms of overactive bladder, but occasionally it may become less effective because of desensitisation. If so, medicine may be needed to control symptoms before making a decision to remove the SNM system. The committee concluded that no other treatments (including medicine) for overactive bladder should be needed with Axonics SNM system, unless symptoms are no longer adequately controlled.

Overactive bladder is common in women who have been pregnant or who are postmenopausal. It is more common in older people, people with obesity and may be common in disabled people. The instructions state that Axonics SNM system is contraindicated for patients who are unable to operate it. So, the technology may not be suitable for all patients, which could include some disabled people or people with cognitive impairment. The clinical experts explained that the device can be recharged by a carer. The committee noted that when a carer is not available to help with recharging Axonics SNM system, the option of a non-rechargeable SNM system would still be available.

The clinical experts said that the smaller size of the Axonics SNM system compared with the non-rechargeable device makes it more suitable for people with low body mass index. Axonics SNM system is conditionally safe to be used with 1.5T and 3T full-body and head coil MRI. The MRI compatibility of the device means that most people with overactive bladder who may need future MRI scanning do not need to have their device removed, avoiding replacement surgery. This consideration was also relevant to people with chronic conditions such as multiple sclerosis, who are likely to need regular MRI scans.

The clinical experts explained that people are told about the advantages and disadvantages of the rechargeable and non-rechargeable systems before a device is implanted. These include uncertainty about device longevity and possible causes for device failure. The longer battery life of Axonics SNM system may appeal to a person using the device. The committee concluded that this is ultimately the person's decision.

Clinical experts stated that Axonics SNM system is easy to use, for the person and the healthcare professional, and needs little in the way of additional training. They also explained that the implant procedure for the Axonics SNM system is minimally invasive and no more complex than for the non-rechargeable device. A clinical expert explained that people with memory problems may prefer the non-rechargeable device but that people with mild cognitive impairment may be able to have an Axonics SNM system if support is available. The committee concluded that Axonics SNM system could be used by most people, particularly if a carer can help.

The committee accepted the EAC's preferred cost model, which showed that Axonics SNM system becomes cost saving at 6 years after implant. The committee acknowledged the uncertainties in extrapolating data collected over 2 years to a 15‑year time horizon but considered this approach to be suitable for decision making. The committee acknowledged that the failure to include the cost of battery disposal in the cost modelling was a limitation.

The company explained that the device warranty lasts for 12 months. The clinical experts explained that people are advised to include their device in insurance policies to cover loss of, or damage to, the remote or charger. The committee considered that, based on the company's confidence in the longevity of the device and the results of the cost modelling, the warranty should be extended by the company to at least 6 years.

After consultation, the EAC investigated if other parameters and scenarios affected the cost modelling. The rate of surgical site infection used in the model, which had been different for the Axonics SNM system than the non-rechargeable SNM system, was changed to 1% for both groups. The clinical experts explained that in practice, rates of surgical site infection are low, and they had not seen an obvious difference in surgical site infection rates between Axonics SNM system and the non-rechargeable SNM system. The committee concluded that the rates of surgical site infection used in the model should be the same for both the intervention and comparator technologies. It agreed that 1% was appropriate given the low rate of surgical site infection in clinical practice.

After consultation, the committee considered the suggested changes to the model. The clinical experts explained that Axonics SNM system was smaller than the non-rechargeable system, so it was reasonable to assume that people would have fewer pain-related events. Also, the company explained that the clinician programmer is provided free of charge, so it was correct that no cost for this was included in the model. The committee concluded that fewer pain-related events and no cost for the clinician programmer were appropriate assumptions in the cost modelling.

The committee considered the possible effect of a longer lifespan for the non-rechargeable comparator SNM system on the cost-effectiveness modelling. But the clinical experts explained that 4.4 years accurately reflected their own clinical experiences. The committee concluded that an estimated lifespan of 4.4 years for the non-rechargeable SNM system was appropriate for the cost-effectiveness modelling.

The EAC's sensitivity analyses identified time to device replacement as a key driver of cost savings. The committee concluded that Axonics SNM system is cost saving only if it lasts longer than the non-rechargeable device.

The EAC's revised cost modelling estimated that over 15 years, using Axonics SNM system for managing refractory overactive bladder is associated with an estimated cost saving of £6,025 per person in the base case. It showed that cost savings depended on the battery life of Axonics SNM system lasting longer than around 6 years after implant. A battery life of more than 6 years increased the amount of cost savings progressively from 6 years after implant. The committee noted that there was some uncertainty about the battery life beyond 6 years, because there was little published evidence about this. Taking into account Newcastle EAC's technical assessment and expert advice, the committee agreed that the battery is likely to last for at least 6 years. It concluded that Axonics SNM system is cost saving compared with standard care. However, the maximum level of cost savings is uncertain without more evidence about the battery life beyond 6 years.

Further evidence on the long-term clinical effectiveness, quality-of-life benefits and the device longevity of Axonics SNM system in people with refractory overactive bladder would be welcomed. It is recommended that clinicians routinely collect clinical and procedural outcome data on SNM systems, including Axonics. Ideally this should be a national registry set up with a professional society.