ACTION DUCHENNE
INTERNATIONAL
CONFERENCE
2015
Steroids in Duchenne muscular dystrophy
1. The use of steroids in DMD.
2. FOR-DMD steroid trial, does it still matter?
3. Research update on steroids
Dr Henriette van Ruiten
Clinical Research Associate
The John Walton Muscular Dystrophy
Research Centre
Newcastle upon Tyne
Duchenne Muscular Dystrophy (DMD)
• Affects 1 in 3500 newborns
• In UK,
• 100 boys are born with DMD each year
• There are 2500 patients with DMD
• Caused by mutation in the dystrophin gene,
• Absence of dystrophin in muscle fibres
• Clinically characterised by progressive muscle wasting
Current treatments
Pharmacological treatments
Treatment of complications
Respiratory care
Cardiac management
Orthotic and orthopaedic approach
Pharmacological treatments
Steroids
• Also called corticosteroids or
glucocorticoids.
• Man made version of hormones normally
produced by the adrenal glands
• Steroids are mainly used to reduce
inflammation and suppress immune system
• Used in conditions such as asthma, arthritis,
eczema etc)
Why are steroids used in DMD?
• Only medication currently available for all which
slows the decline in muscle strength in DMD
Steroids – history of use
First report on steroids in DMD
• In 1974 Drachman et all. (Lancet) first prescribed
steroids to 14 boys with DMD in USA.
• Recorded an improvement in motor power
and muscular activities in 8 out of 14 boys.
Steroids in the UK:
•
Part of routine care in the last 15 years
•
“Gold Standard” for treatment of DMD as per
Standard of care guidelines (Bushby et al, 2009)
Steroids – which?
Steroids used in DMD are prednisolone and
deflazacort.
Prednisolone
• Available in both tablet and liquid form
• Daily prednisolone more effective than
intermittent in improving muscle strength (North
Star data)
• Intermittent prednisolone has less side effects.
Steroids – which?
Deflazacort:
• Only available in tablets
• Not available in all countries, more expensive
• Daily deflazacort is ? fewer side effects (weight gain)
Steroids – which is best?
 No consensus which steroid regime is best
Deflazocort daily
Prednisone daily
Prednisone 10 days on/10 days off
Prednisone weekend doses
Prednisone 10mg/kg (we)
Steroid – prescription chaos
 Worldwide 105 clinics which prescribe 29 different
steroid regimes
 In the UK prednisolone is most commonly prescribed
with 50:50 split between daily and intermittent
regimes. Minority prescribe deflazacort.
 Current trial FOR DMD – to end the prescription
chaos
FOR DMD STUDY (www.for-dmd.org)
 International study (US, Canada, UK,
Germany, Italy)
 This study compares three ways of giving steroids
to young boys (age 4-7) with DMD
 Steroids studied:
 Prednisolone daily 0.75mg/kg
 Prednisolone (0.75mg/kg) 10 days on/10 days off
 Deflazacort daily 0.9mg/kg
 Aim: to determine which increases muscle strength
the most and which has the fewest side effects
 End date is September 2016
Steroids – balance between
benefits and risk
Benefits of Steroids
Early increase in motor skills and energy,
Delay loss of milestones
Boys on steroid are 5x more like to walk at age 12-17 than
boys not on steroids (Treat NMD data)
Improve upper arm function
Important for feeding, driving wheelchair, self care and
using phones/computers
Benefits of steroids
Strengthen muscles in the back
Reduces likelihood of spinal surgery from 90% to 10%
Strengthen breathing muscles
Steroids improve vital capacity (FVC)
Low FVC linked to need for breathing support
Protect the heart
However, response to steroids is variable
 Approx 1-2% of boys do not respond to steroids
Side effects of steroids
Considerable but predictable
Side effects:
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Behaviour problems
Weight gain
Cushingoid appearance
Vertebral fractures
Immunosuppression
Short stature
Delayed puberty
Cataracts
Hypertension
GI upset
 Are significant
 Require proactive
management
• Behavioural guidance
• Prophylaxis/treatment of
osteoporosis
• Regular follow up (BP, glycosuria,
eye check, physical exam)
• Flue jabs
• Avoid live vaccines
Starting steroids
 Around the plateau phase of motor function. This
usually happens around the age of 4-5yrs old.
 With time steroid dose is adjusted according to
benefits and side effects
 Try and prevent/treat side effects before reducing
dose
 In older less ambulant boys steroids may still be of
benefit; eg in improving upper body strength,
reducing the risk of scoliosis and stabilizing
respiratory function.
General advice on taking steroids
 Before taking steroids: check chickenpox immunity,
bone scan and an eye check.
 Once the steroids have been started: regular review
for monitoring of side effects, and a regular bone
scan
 Do not stop steroids suddenly, must be reduced
gradually.
Emergencies in boys with DMD on steroids
 If vomiting or unable to take steroids – contact GP
or the muscle team. Your son may need to be given
steroids by injection.
 Always carry your steroid warning card
 Information about emergency management for boys
with DMD is available from AD (Action Emergency
pack) and Parent Project (Emergency information
card)
When to stop steroids
 The age to stop steroids needs to be decided
individually. It may be necessary to change or stop
the steroids because of side effects. In other
situations, they can be used for many years, beyond
the age at loss of ambulation.
 Never stop steroids suddenly!
Research update
FOR DMD trial - update
 Recruitment target = 225 boys
 End of recruitment is august 2016
 Current no of boys enrolled = 156
 Boys can be in exon skipping trial AND FOR DMD
 Results expected 2018
 Results will provide evidence based guidance on best
steroid treatment in DMD
 Standardise steroid treatment
 Important for current and future clinical trials
Research update
 Starting steroids early (< age 4):
 Merlini et al 2012
 Prolongs ambulation compared to starting steroids
later.
 Next generation steroids:
 VBP15 – Dr Eric Hoffman USA
 Replacement drug for steroids. New drug with a
similar mode of action but without side effects
 In addition it has been shown to stabilise the
structure of muscle cells
Research update
 Initial results:
 Preclinical: beneficial in mice (better than prednisolone)
 Phase I: results awaited
 Phase 2 (boys with DMD)
 Phase 2a: In USA, steroid naïve boys
 Phase 2b: In Europe
Summary
 At the moment steroids are the only “treatment”
available for all boys with DMD.
 The benefits are indisputable however they come
at a cost.
 FOR DMD study: to provide an “evidence based”
guidance on steroid treatment.
 Next generation steroids – very promising
Thank you
Any questions?