Way Ahead 2012;16(3):2-3
MS research showcased at AAN meeting
- Menopause and MS
- Pregnancy and DMTs
- Combining glatiramer acetate and beta interferon
- Beta interferon for early stage MS
- Oral or iv steroids for relapse
- BG-12 phase III results
MS Trust research news
- Fingolimod safety review
- NICE recommends fingolimod
- Licensing applications for teriflunomide and BG-12
- NICE considers teriflunomide
MS research showcased at AAN meeting
The 64th annual meeting of the American Academy of Neurology (AAN) took place in April in New Orleans. The results presented below should be regarded as preliminary until published in a peer-reviewed journal. Abstracts are available online at www.abstracts2view.com/aan/
Menopause and MS
The clinical course of MS does not appear to be significantly affected by the menopause. In this study, 128 pre-menopausal women (aged 38 to 46) were compared with 78 menopausal women (aged 54 to 62). Clinical measures, such as change in EDSS score and T2 lesion volume, were monitored over two years but were not significantly different for the two groups.
They were also compared to two groups of men of similar ages to control for any effect of age on MS disease course. Menopausal women reported deteriorating symptoms although men of the same age did not. Overall, this suggests that these symptoms, such as increased fatigue, are directly related to the menopause rather than to a change in MS.
Pregnancy and DMTs
Women with MS are usually advised to stop disease modifying treatment (DMT) before conceiving but accidental pregnancies still occur. A study in Germany of seven women, who received natalizumab during the third trimester, showed that mean birth length, mean birth weight and mean gestational age were not affected. Two babies were born with profound anaemia but recovered fully.
In a second study, a literature review identified 761 beta interferon, 97 glatiramer acetate, and 35 natalizumab exposed pregnancies. It was reported that beta interferon exposure was associated with lower mean birth weight, shorter mean birth length, and preterm birth, but not caesarean delivery, congenital anomaly or spontaneous abortion.
There were fewer studies for glatiramer acetate and natalizumab but neither drug was associated with lower mean birth weight, congenital anomaly, preterm birth or spontaneous abortion.
Although encouraging, the researchers cautioned that these studies are small and do not follow the children's development in the longer term.
Combining glatiramer acetate and beta interferon
For people with relapsing remitting MS, little clinical benefit was seen after taking both glatiramer acetate (Copaxone) and interferon beta 1a (Avonex) compared with taking either drug alone.
In a large randomised placebo-controlled trial (CombiRx), 1,008 people were followed over three years. The average age of participants was 38, average disease duration was 4.3 years and time since diagnosis was just over a year at the time that they enrolled in the study.
Annualised relapse rates, time to first relapse, rate of disability progression, brain lesion counts and volumes were not significantly different between the groups. Serious adverse events were similar in all groups.
Beta interferon for early stage MS
In the REFLEX (REbif FLEXible dosing in early MS) trial, people who received interferon beta 1a (Rebif) soon after their first clinical demyelinating event, were less likely to progress to clinically definite MS after three years compared with those who received placebo.
The trial involved 517 people who had experienced a first clinical episode suggestive of a demyelinating event, such as tingling or muscle weakness, along with at least two clinically silent brain lesions detected by MRI. Participants were randomly assigned to receive beta interferon, either three times a week or once a week, or placebo for 24 months or until a second clinical episode.
At the end of 24 months, all participants were eligible for the extension study (REFLEXION). Those originally receiving placebo, who did not have clinically definite MS, were switched to the three times weekly dose. Those on once weekly and three times weekly beta interferon, who had not reached clinically definite MS, continued their initial regime.
At 36 months, the level of clinically definite MS was 41% for the delayed-treatment group (those who had switched from placebo to three times weekly treatment), 28% for the group receiving once weekly treatment for three years and 27% for those receiving three times weekly treatment for three years.
These results suggest that treatment should be started immediately rather than waiting for a second event to confirm a diagnosis of MS.
Following publication of these results, the European Union approved Rebif for the treatment of clinically isolated syndrome (CIS) which brings it into line with the other beta interferon drugs.
Oral or iv steroids for relapse
People with MS experiencing a relapse were given either oral or intravenous methylprednisolone. After 28 weeks, 73% given oral medication showed at least a one point improvement in the EDSS scale compared with 70% of those who were treated with the drug intravenously (iv). Overall, the outcomes and adverse events were equivalent in the two groups. However, oral therapy was found to be more convenient.
BG-12 phase III results
The results of the phase III, double-blind CONFIRM trial of oral dimethyl fumarate (BG-12) for people with relapsing remitting MS were announced.
The 1,430 participants had average disease duration of eight years and a mean EDSS score of 2.6. Fewer than 30% had previously been treated with another disease modifying therapy.
Over the two year study, 41% of people in the placebo group experienced relapses, compared with 32% of those on glatiramer acetate, 29% of those in the twice-daily BG-12 group and 24% of those taking the drug three times a day. Overall, both doses of BG-12 gave similar results and both were more effective than placebo in a variety of endpoints.
MS Trust research news
Fingolimod safety review
In April, the European Medicines Agency (EMA) reviewed treatment with the oral disease modifying drug fingolimod (Gilenya) after there were reports of people experiencing heart problems and cases of sudden or unexplained deaths.
When beginning treatment with fingolimod, the EMA now recommends:
- heart activity should be monitored by an electrocardiogram (ECG) before the first dose is given and continuously for the first six hours
- monitoring should continue throughout the night if heart problems, such as bradycardia or atrioventricular (AV) block, do not resolve.
In addition, fingolimod should not be prescribed to people with a history of cardiac problems, certain conditions affecting blood supply to the brain or to those who take medication to lower heart rate. If treatment is considered necessary in people with these conditions, heart activity should be monitored as above.
NICE recommends fingolimod
NICE (the National Institute for Health and Clinical Excellence) has issued its final guidance for the prescribing of fingolimod by the NHS in England and Wales. Fingolimod has been approved as a treatment for highly active relapsing remitting MS in adults who have an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year despite treatment with beta interferon.
Licensing applications for teriflunomide and BG-12
The European Medicines Agency (EMA) has accepted marketing authorisation applications (MAAs) for the oral disease modifying treatments, teriflunomide (Aubagio) and BG-12 (dimethyl fumarate), from their manufacturers, Genzyme and Biogen respectively. This is the first step in the licensing process.The EMA will now review each drug and, if satisfied that the new medicine is effective, safe and meets manufacturing quality standards, a licence will be issued. There has been no indication when a decision will be given.
NICE considers teriflunomide
NICE have begun drafting the scope for the health technology appraisal of teriflunomide ahead of possible licensing. The appraisal is at a very early stage and the MS Trust is actively involved.