American Academy of Neurology update 2009
Round-up of research results from the 61st annual meeting of the American Academy of Neurology
The 61st annual meeting of the American Academy of Neurology took place in Seattle April 25 to May 2.
This annual meeting, a showcase for the latest developments in scientific research, was attended by more than 10,000 of the world's leading researchers and neurologists.
Professor David Miller of the Institute of Neurology in London was awarded the John Dystel Prize for Multiple Sclerosis Research for his pioneering work using MRI and imaging techniques.
Professor Miller has worked in this area and published widely on MS since the early 1980s. In awarding the prize at the recent American Academy of Neurology (AAN) meeting in Seattle, Dr Henry McFarland Chief of the Neuroimmunology Branch at the National Institute of Neurological Disorders and Stroke, said "Much of our understanding of MS through the use of MRI has its roots in David's laboratory."
The Dystel Prize is given jointly by the AAN and the American National MS Society.
More than 380 presentations concerned multiple sclerosis alone, covering all areas of MS research, from basic laboratory studies aimed at furthering our understanding of MS, through to early announcements of clinical trial results for experimental treatments and new data for existing therapies.
Abstracts from the meeting can be viewed on the AAN website.
Here is a summary of the highlights:
New oral treatments for relapsing remitting MS
The race is on to be the first tablet treatment for relapsing remitting MS, so clinical trial data for two experimental, oral treatments, cladribine and fingolimod, were eagerly anticipated. Both are currently in Phase III trials and manufacturers plan to submit these drugs for licensing in 2009. NICE (the National Institute for Health and Clinical Excellence) has already announced that it may include fingolimod and cladribine in its next round of appraisals.
Fingolimod (FTY720)
Cladribine
In an extension of a phase II study, people continued to take fingolimod, including those previously taking placebo. Relapse rates remained low with up to 70% remaining relapse-free after 4 years [P06.128].
TRANSFORMS is a one year phase III study comparing two doses of fingolimod with interferon beta-1a (Avonex). 80 to 83% of the fingolimod groups remained relapse-free compared with 69% of those on interferon beta-1a. These data echo results previously announced in a company press release in December 2008 showing that the relapse rate at one year was 52% lower in people taking fingolimod compared to those taking interferon beta-1a [S21.004].
Cladribine is currently licensed in an injectable form to treat certain types of leukaemia. The manufacturers have developed a tablet formulation for the treatment of MS.
Results were presented for the two year phase III study, CLARITY, which involved more than 1300 people with relapsing remitting MS. In this study, two different dosing routines were compared to placebo: cladribine was taken once daily for five consecutive days, either twice a year for the two years (low dose) or four times in the first year and twice in the second year (high dose).
Those in the low dose group experienced a 58% reduction in annual relapse rate compared to placebo, while those in the high dose group experienced a 55% reduction. Other clinical measures showed similar results [LBS.001].
These two oral drugs are showing promise in clinical trials, but there are safety issues associated with both treatments which will need further clarification.
Other new, experimental treatments
Alemtuzumab (Campath)
Stem cells
Alemtuzumab is currently licensed to treat a type of leukaemia. It is given by iv infusion and is in phase III clinical trials for relapsing remitting MS.
Researchers announced further analysis of data from the phase II CAMS223 study which compared interferon beta-1a (Rebif) with two dose levels of alemtuzumab in early, active relapsing remitting MS. Sustained reduction in disability (SRD), defined as a decrease in EDSS (a clinical measure of disability) of one point or more for more than six months, was twice as likely in those taking alemtuzumab as those taking interferon beta-1a. The researchers suggest that alemtuzumab may halt progression of disability and stably reverse pre-existing neurological impairment, but further study is needed to confirm this [P06.145].
A further presentation reported that the improvements seen after two annual cycles of alemtuzumab were still present 2 years after the last dose [P07.143].
Canadian researchers reported data from 1-8 years of follow-up for 16 people with an aggressive form of MS who had received autologous stem cells (recipients receive their own stem cells) following suppression of their immune system. 6/16 improved, 3/16 worsened and 7/16 remained unchanged. The degree of improvement varied widely between those treated, but was related to how long they had had MS, those who had had MS for longer also took longer to show any perceived benefit [P02.145].
New data for existing treatments
Natalizumab (Tysabri)
- Sophisticated MRI techniques provided evidence that natalizumab treatment may promote remyelination [P03.071].
- Further analysis of data from a clinical trial which compared natalizumab with placebo investigated reductions in EDSS scores (a scale used to measure disability), suggesting improved disability. Natalizumab significantly increased the probability of a one point EDSS improvement over 2 years by 69% compared to placebo [P06.131].
- Progressive multifocal leucoencephalopathy is a rare but potentially fatal side effect of natalizumab treatment. In a presentation of postmarketing surveillance data for natalizumab, Dr Bozic, a representative of the manufacturers Biogen, provided evidence that the risk of PML is lower than previously thought and the infection less severe. Following clinical trials, the risk of developing PML had been calculated as 1 in 1000 but data from general use suggest a risk closer to 1.2 in 10,000 [S11.005].
- Oral herpes virus eruptions were 3 times more likely in patients with multiple sclerosis who were taking natalizumab than in multiple sclerosis patients on no therapy [P03.163].
Mitoxantrone
Beta interferon 1a (Avonex)
Combination therapy
Economic impact of early mobility impairment
Natalizumab is licensed to treat highly active relapsing remitting MS. 46 presentations provided further data on natalizumab. These included:
Mitoxantrone is a chemotherapy drug, used to treat aggressive forms of relapsing remitting MS.
Previous studies have also shown that the people with MS treated with the drug have an increased risk of developing leukaemia. Those studies showed that acute leukemia occurred in 0.07 percent to 0.25 percent of MS patients taking mitoxantrone. This retrospective study of 2,854 Italian people with MS receiving the drug found that leukemia occurred in 0.74 percent, three times higher than previously thought [LB3.002].
Neurologists continue to debate whether to start disease modifying treatments immediately after the first symptoms MS or to delay treatment until confirmed diagnosis.
This ten-year follow up showed that people treated immediately after their first episode of MS symptoms had significantly less chance of experiencing a second attack compared those with delayed treatment [P06.137].
Methylprednisolone is a steroid, typically used to treat MS relapses.
In this study, methylprednisolone given in pulses every four weeks, was combined with interferon beta 1a. Those who received both drugs had 38 percent fewer relapses over the three year study, compared to those who received interferon beta 1a alone. There was a high drop out rate on the study - in the group receiving methyprednisolone because of side effects, and in the placebo group because of lack of effect. The researchers acknowledged that these results need to be confirmed in larger studies [LB3.002].
The same clinical trial has recently been published in the Lancet - see news item
Researchers used data from a registry of more than 8000 North Americans with MS to assess the impact of impaired mobility on employment and income. As might be expected, mobility correlated significantly with employment; furthermore even minor mobility impairment experienced at otherwise low disability level appeared to contribute to the loss of productivity and income and the greatest changes in income levels occurred when people with MS went from normal mobility to minimal mobility impairment [P02.127].
