‘Real life’ experience with rivastigmine

The Swedish Alzheimer Treatment Study is a non‐blinded investigation of the long‐term use of cholinesterase inhibitors for Alzheimer's disease in routine clinical practice (Acta Neurol Scand 2009;119:180‐5). In a subgroup of 217 patients with mild to moderate disease (mean baseline Mini‐Mental State Examination (MMSE) score 22.9, Alzheimer's Disease Assessment Scale ‐ cognitive sub‐scale (ADAS‐cog) 18.5), treatment with rivastigmine was associated with an initial increase in MMSE score at two months, followed by a steady decline with a final difference of 1.84 points below baseline overall at 24 months. There was a corresponding worsening of ADAS‐cog scores. However, MMSE and ADAS‐cog scores were stable or improved in approximately 40 per cent of patients and rates of decline were lower than predicted from historical data in the absence of treatment.

Rivastigmine treatment was continued for two years in 62 per cent of patients; the commonest reasons for stopping treatment were admission to a nursing home and adverse reactions. Cognitive outcomes were worse for patients admitted to nursing homes.

By contrast with UK guidance, the authors conclude that the cognitive and functional benefits of rivastigmine in patients with mild to moderate dementia may be substantial.

Monitoring the response to interferon

Monthly MRI monitoring suggests that perhaps half of patients with relapsing‐remitting multiple sclerosis have a long‐term response to treatment with interferon beta‐1b (Arch Neurol 2009;66:39‐43).

In this retrospective study, MRI scans were carried out monthly on 15 patients for six months before and for 36 months during treatment with interferon beta‐1b 250μg on alternate days. Eight had a reduction of at least 60 per cent in the number of contrast‐enhancing lesions; of these, two relapsed with sustained progression of disability score. The remaining patients were classed as non‐responders; each had at least one exacerbation and four had relapses. However, two patients with no initial response eventually reached and maintained a 60 per cent reduction in lesions after six months. An initial response was not sustained in a further three patients. No factors predicting outcome were identified, including neutralising antibodies.

Follow‐up after natalizumab

There is no evidence of rebound deterioration in multiple sclerosis after stopping treatment with natalizumab, say US neurologists (Neurology 2009;72:396‐401).

They followed up 23 participants in Phase III trials for 14 months after discontinuing natalizumab. During this period, most were prescribed other medication (usually interferon beta‐1a but also glatiramer acetate). Two patients relapsed, one of whom was taking no treatment, but overall the reduction in relapse rate observed during natalizumab therapy continued. There was no change in the number or volume of contrast‐enhancing lesions on MRI or in immunological status; there were no cases of progressive multifocal leucoencephalopathy.

Combination therapy

There is no advantage in adding immunosuppressants when interferon beta‐1a alone fails to control disease activity in patients with multiple sclerosis, the Avonex Combination Trial has shown (Neurology 2009;72:535‐41).

A total of 313 patients with evidence of continuing disease activity after at least six months of interferon therapy continued their treatment and were randomised to receive placebo or additional treatment with oral methotrexate 20mg weekly and/or bimonthly intravenous methylprednisolone 1g daily for three days. After 12 months, there were no significant differences between the treatment arms in the number or volume of lesions on MRI or clinical relapses. Combination therapy was largely well tolerated though there were signs of declining respiratory function in patients taking methylprednisolone. Methylprednisolone also significantly reduced the development of neutralising antibodies.

MS care and risk sharing schemes

Beta interferons and glatiramer acetate are available to NHS patients with multiple sclerosis under risk sharing schemes in which funding is conditional on monitoring outcomes for 10 years and price adjustments are made according to the results. A review of the first three years of these schemes is optimistic about the prospects for success (BMC Neurology 2009;9:1 doi: 10.1186/1471‐2377‐9‐1).

Seventy‐one centres participate in the schemes, admitting 5560 patients between 2002 and 2005; data are available for 4871 patients with follow‐up of 9 to 44 months. Eighty‐six per cent had relapsing‐remitting disease and the remainder had a relapsing form of secondary progression. Patient characteristics and disease profile was similar to that in clinical trial populations.

The cumulative proportions of patients stopping all treatment were 7.5 per cent after one year, 12.5per cent after two and 14 per cent after three. Switching between treatments increased from 3.9 to 13.6 per cent over the same period.

Over three years, the proportion of patients with secondary progressive MS increased from 14 to 25 per cent. Mean disability score increased slightly but there was no change in most patients and an equal numbers of patients experienced progression and regression. The mean annual number of relapses decreased from 1.43 at baseline to 0.66 at the first annual review.

The authors say their review shows that risk sharing schemes are feasible in the NHS. However, they warn that the most important threat to the NHS's ability to determine the cost effectiveness of these treatments are tensions due to the conflicting interests of stakeholders.

SMC accepts lacosamide as add‐on for adults with partial seizures

The Scottish Medicines Consortium (SMC) has accepted lacosamide (Vimpat) for use within NHS Scotland as adjunctive therapy in the treatment of partial‐onset seizures with or without secondary generalisation in patients with epilepsy aged 16 years and older.

SMC says in a Press release that the number of eligible patients was estimated to be 10 256 in year one rising to 10 318 in year three.

The efficacy of lacosamide as adjunctive therapy at recommended doses (200mg daily, 400mg daily) was established in three multicentre, randomised, placebo‐controlled clinical trials with a 12‐week maintenance period. Overall the proportion of patients with a 50 per cent reduction in seizure frequency was 23 per cent, 34 per cent and 40 per cent for placebo, lacosamide 200mg daily and 400mg daily, respectively. In addition, results from an open‐label extension study demonstrate long‐term retention; of the 370 patients enrolled, 77 per cent were still taking lacosamide after one year.

RCP vs NICE on use of antipsychotics in dementia

Both NICE and the Royal College of Psychiatrists have published guidelines on the use of antipsychotics for the management of behaviour disorders and psychiatric symptoms in patients with dementia, prompting investigators from Northampton to survey old age psychiatrists for their views (Psychiatric Bull 2009;33:57‐60).

About one‐third of 648 questionnaires were returned, mostly from NHS community and in‐patient settings. Of these, two‐thirds believed NICE guidance placed clinically inappropriate restrictions on the use of antipsychotics whereas the College's guidance supported their use for selected patients. Again, two‐thirds of comments on NICE guidance were negative (too restrictive for secondary care, overemphasises risk, unrealistic) whereas 78 per cent were positive about the College's guidance, praising it as balanced, practical and useful to justify treatment decisions. Almost all (96 per cent) respondents disagreed that antipsychotics should never be prescribed for this indication. The most widely prescribed antipsychotics were quetiapine, haloperidol, risperidone, amisulpride and olanzapine.

The authors note that, the views of respondents notwithstanding, the recommendations of NICE and the College are similar. They speculate that antipathy to NICE may be due to its dogmatic tone, its origins as an organisation founded by the Government and the inclusion of non‐pharmacological interventions that lack an evidence base.

Why stop clozapine?

Analysis of patient records in a London NHS Trust has demonstrated the serious risks of treatment with clozapine (Br J Psychiatry 2009;194:165‐7).

Investigators compared reasons for discontinuing treatment with clozapine in 161 patients matched to patients who discontinued long‐acting risperidone injection. The mean duration of treatment was 12 months for clozapine (mean final dosage 360mg daily) and six months for risperidone (35mg daily).

Discontinuation of clozapine was due to adverse effects in 35 per cent of cases compared with 20 per cent for risperidone but lack of efficacy accounted for 2 and 37per cent of dis‐continuations respectively. However, the risk of discontinuation due to death was seven times greater with clozapine (13 vs 2 per cent).

About half of deaths among patients treated with clozapine were due to cardiovascular causes or pneumonia, possibly associated with smoking. This highlights the importance of preventing and treating physical illness and smoking in patients with schizophrenia, the authors conclude.

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