124th ENMC International
2nd - 4th April 2004, Naarden, The Netherlands
Treatment of Duchenne muscular dystrophy - defining the gold
standards of management
35 participants representing parents, funding agencies and
clinicians involved in the care of children with DMD from
Belgium, Canada, Denmark, Finland, France, Germany, Italy,
the Netherlands, Spain, Sweden, the UK and the USA met in
Naarden from 2nd - 4th April 2004.
The meeting was held under the auspices of the ENMC Clinical
Trials Network, and with the additional support of the
United Parent Project. The aims of the workshop were to
define the need for clinical trials in Duchenne Muscular
Dystrophy (DMD) and develop a protocol for such trials,
relating primarily to the use of steroids (prednisolone,
prednisone and deflazacort) in DMD. The meeting heard that a
major worry for parents is the lack of availability of
steroids at all in some countries, the multiplicity of
steroid regimes used and the problems of getting firm
information about which type of steroid or which regime for
using steroids was best.
This was reflected in the variation in practise amongst the
participants at the Workshop, some of whom did not use
steroids at all, and between the rest there were at least
seven different regimes for giving steroids.
The meeting was divided into three parts. First, the
evidence for the use of steroids in DMD was considered.
Second, the meeting split into small groups for the
development of various aspects of a protocol that could be
used for a trial of steroids or for the monitoring of their
use in clinical practice, and third a strategy to develop
and fund a trial or trials in DMD were considered.
There can no longer be any doubt that use of steroids in
ambulant children with DMD alters the natural history of the
condition. Children treated with daily steroids are likely
to walk for longer, have improved respiratory function, may
avoid the need for spinal surgery and might have better
heart function than untreated children. Benefits of starting
steroids in children who have already lost ambulation are
not yet established. The two main types of steroid used
(prednisone/ prednisolone and deflazacort) appear to be
Side effects seen with the long term use of steroids in DMD
use include weight gain, (which may be less prominent using
deflazacort) loss of height, asymptomatic cataracts (with
deflazacort predominantly) and thinning and possibly
fractures of the bones. Nonetheless, many centres have used
daily steroids for many years, and ways to help to avoid or
treat many of these side effects are available.
There are alternative ways to use steroids to try and
minimise the side effects. These include giving a lower
dose, or using steroids in an intermittent way (on alternate
days, for periods such as 10 days on and 10 days off, or at
the weekends only). The rationale behind using these other
regimes is to give the body a rest from steroids at times,
and/or with some but not all of the regimes to give a lower
People using all of these different regimes report that they
have a positive effect in improving strength and function in
DMD. However none of them have been tested formally against
daily steroids to see if there is a difference in how
effective they are and what the actual level of reduction in
side effects is.
It was agreed steroids are the gold standard of treatment in
DMD against which other treatments should be judged. To
provide answers on the relative merits of the different
regimes a trial is needed to look at the efficacy and side
effects of a range of regimes compared to daily steroid over
a long period of time. Protocols were discussed that would
allow differences in strength and function to be picked up
and that would monitor for side effects while also trying to
prevent them as much as possible. It was felt to be very
important to monitor effects on quality of life as well as
muscle strength and function. Alongside testing different
steroid regimes, the ideal trial would also look at the best
way to prevent the development of heart problems and
protection of bone strength. As this trial will need to
recruit large numbers of patients, a multinational effort
will be required and different national funding agencies are
likely to be involved.
In advance of this trial, it was felt that it would be
useful to develop some basic advice about the monitoring and
management of possible side effects of steroids in DMD.
Problems with bone density and weight are two of the major
concerns as children with DMD can have problems in these
areas even without steroids. For example, even young
children with DMD may have bones which are less strong than
normal. This is believed to be because they are less active
than other children. Exercise helps bones to grow strong, so
boys with DMD should be encouraged to be active. It is also
important for growing bones to have proper levels of vitamin
D and calcium. The best way to achieve this is by diet and
sunshine- supplements are not as well absorbed. Because of
their weaker bones, boys with DMD may have a higher risk of
breaking their bones, but they heal normally. It is though
important that broken bones are treated with as short
periods of immobilisation as possible.
Using steroids in DMD has multiple effects on bones.
Increased strength leads to more exercise and can strengthen
the bones. However, steroids are known to have a bone
weakening effect and this may become more prominent with
long term use. Again, diet and sunshine are currently the
best way to try and prevent problems. Broken limbs in
steroid treated boys can be treated the same way as boys not
on steroids. In long term use of steroids some people have
seen weakening or compression of the back bones and this can
rarely cause pain, though it can be treated. The issue of
prophylaxis for these problems will be the topic of further
Weight is another worry for people using steroids. Boys with
DMD sometimes have a tendency to too much weight gain. This
may partly relate to their lower levels of activity. So the
tendency to gain weight can be most when activity is
declining. In itself, of course, increased weight can also
make walking more difficult. Sweets and fast foods are best
avoided where possible. Alternatives to these kinds of
treats are available, and low fat or low calorie
alternatives to many foods can be easily obtained. The need
to control weight is even more important in children with
DMD treated with steroids. Appetite increases immediately in
many people who take steroids, and the family needs to be
ready for that. The highest risk of weight gain on starting
steroids is in the first few months so if particular
attention can be paid to healthy eating at this stage and
continued with the steroid treatment, problems may be less.
Additional diet issues for children on steroids include
adequate calcium and vitamin D.
Further patient information material will be prepared and
This workshop was organised by Prof. Kate Bushby (UK), Prof.
Francesco Muntoni (United Kingdom), Prof. Andoni Urtizberea
(France), Prof. Richard Hughes (United Kingdom) and Prof.
Robert Griggs (U.S.A.).
Other participants were:
Dr. Anna Ambrosini (Italy), Dr. Anne d’Andon (France), Prof.
Corrado Angelini (Italy), Dr. Carole Bérard (France), Dr.
Enrico Bertini (Italy), Dr. Doug Biggar (Canada), Dr. John
Bourke (United Kingdom), Dr. Jaume Colomer (Spain), Prof.
Denis Duboc (France), Prof. Victor Dubowitz (United
Kingdom), Dr. Michelle Eagle (United Kingdom), Prof.
Brigitte Estournet (France), Dr. Kevin Flanigan (U.S.A.),
Dr. Patricia Furlong (U.S.A.), Dr. Nathalie Goemans
(Belgium), Dr. Imelda de Groot (The Netherlands), Dr. Sharon
Hesterlee (U.S.A), Dr. Anneke van der Kooi (The
Netherlands), Prof. Rudolf Korinthenberg (Germany), Dr.
Adnan Manzur (United Kingdom), Dr. Richard Moxley (U.S.A.),
Prof. Giovanni Nigro (Italy), Dr. Helena Pihko (Finland),
Dr. Michael Rose (United Kingdom), Dr. Thomas Sejersen
(Sweden), Ms. Birgit Steffensen (Denmark), Dr. Tony Swan
(United Kingdom), Dr. Marcello Villanova (Italy), Ms.
Elizabeth Vroom (The Netherlands) and Dr. Maggie Walter
An extended report of this meeting will be submitted for
publication in Neuromuscular Disorders.
Neuromuscular Centre (ENMC)
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3743 JN Baarn
tel. (31) 35
fax (31) 35 5480499