Parent Project July 2006v5

8/8/2019 Parent Project July 2006v5

1/68

Muscular DystrophyMuscular Dystrophy

Parent Project Muscular Dystrophy2006 Annual Conference

Cincinnati, 2006.

Doug Biggar, MD, FRCP(C)

Bloorview Kids Rehab, Toronto.

Treatment with Corticosteroids


2/68

Why Corticosteroids in DMD?Why Corticosteroids in DMD?

Prednisone shown to change the course of DMD

reduced weakness

preserved motor function

but ..taken daily is best and

side effects common


3/68


4/68

Corticosteroids in DMDCorticosteroids in DMD

Summary:

Corticosteroids help muscle strength

They slow the progression

Start when boys are walking

Best to give every day, once a day

Balanced discussion of benefits and risks More studies are needed


5/68

Derivative of prednisone

Similar effects on:

What is Deflazacort?What is Deflazacort?

immunity

inflammation


6/68

Less:

weight gain

diabetes

osteoporosis?behavior problems

Why Deflazacort?Why Deflazacort?

Same benefits as prednisone but fewer

side effects


7/68

Deflazacort in DMDDeflazacort in DMD

Treatment protocol

Results: Mobility

Pulmonary Function

Scoliosis

Heart


8/68

Arbitrary, 4 6 years of age

When parents tell us:

stairs are more difficult

falling more

difficulty getting up from floor

they are ready

Time to StartTime to Start


9/68

0.9 mgm / kgm / day

Starting DoseStarting Dose

then adjust with: age

weight

side effects


10/68

Deflazacort DoseDeflazacort Dose

Average dose at:

10 years.0.8s 0.18 mg/kg/day




11/68

Deflazacort Group - 48 boysv.s.

No Deflazacort Group - 33 boys

Deflazacort Treatment ofDuchenne Muscular Dystrophy

Deflazacort Treatment ofDuchenne Muscular Dystrophy


12/68

33 boys

age 9 19 years

NoNo Deflazacort GroupDeflazacort Group

concerns about side effects: weight gain

behavior

not walking

other

parental choice


13/68

48 boys

start age 4-6 years

Deflazacort GroupDeflazacort Group

starting dose:

0.9 mgm/kg/day- one dose

1000 units Vitamin D and

750 mg Calcium


14/68

normal weight gain

preserved muscle strength

preserved cardiac function

preserved pulmonary function

delayed or prevented scoliosis

Our Findings Since 90Our Findings Since 90


15/68

Osteoporosis even without steroids

30-70% cataracts, not treated

some behaviour issues- muddy waters

puberty delayed

short stature- good and bad

Our Findings Since 90Our Findings Since 90

:


16/68


17/68


18/68


19/68


20/68


21/68


22/68


23/68


24/68


25/68


26/68


27/68


28/68


29/68


30/68


31/68


32/68


33/68


34/68


35/68


36/68

PreservedPreserved

Muscle FunctionMuscle Function


37/68

WalkingWalking

stop at 9.8 1.8 years

No deflazacort - 33 boys


38/68

treated with deflazacort 48 boys

15 stopped walking at 12.7 s 2.9 years

on average, walk 3-5 years longer

WalkingWalking


39/68

Two Different Protocols forTwo Different Protocols for

DeflazacortDeflazacort

Two Different Protocols forTwo Different Protocols for

DeflazacortDeflazacort

Protocol-N Protocol-T

4-8 Start (years) 6-8

0.6 mg/kg Dose 0.9 mg/kg

20 days on

10 days off

Schedule Daily

As needed for

osteoporosis

Vitamin D

Calcium

1000 units

750 mg

Naples Toronto


40/68

MobilityMobility Walk 10 metresWalk 10 metresMobilityMobility Walk 10 metresWalk 10 metres

9 36/37 (97) 32/32 (100) 15/31 (48)

12 9/26 (35) 19/23 (83) 0/31 (0)

15 3/12 (25) 10/13 (77) 0/31 (0)

Age TorontoNaples Control


41/68

PreservedPreserved

Pulmonary FunctionPulmonary Function


42/68

PULMONARY FUNCTION

0

20

40

60

80

100

10 15 18

FVC

PercentPredicte

Untreated

Treated

Age in years


43/68

Pulmonary FunctionPulmonary Function

At 18 years, boys on deflazacort have:

a better cough

fewer admissions to hospital forpneumonia

no increased infection

and none need nocturnal ventilation


44/68

Delayed ScoliosisDelayed Scoliosis


45/68

Criteria For Spine SurgeryCriteria For Spine Surgery

progressive curve (20 degrees +)

pulmonary function (greater than 40%)


46/68

No deflazacort

27/33 boys done at 13.75 years s 3.6

6/33 not done

3 spines straight at 20 years

3 refused

Scoliosis Surgery in DMDScoliosis Surgery in DMD


47/68

Deflazacort treated:

36 boys older than

13years

4/36 have had surgery

2- compliance issues

2- age 14 and 17 years

Scoliosis Surgery in DMDScoliosis Surgery in DMD


48/68

ScoliosisScoliosis -- Boys after13yrs.Boys after13yrs.ScoliosisScoliosis -- Boys after13yrs.Boys after13yrs.

0%

30%

60%

90%

Naples Toronto Control

30%*

16%*

*p


49/68

Arm FunctionArm Function

Feeding and self care preserved for 5-6 years


50/68

DilemmaDilemma

how long will my sons spine stay

straight?

who will operate on his spine if he

needs surgery?


51/68

Preserved

Cardiac Function

Preserved

Cardiac Function


52/68

C tr l Defl z c ort P

A + + NS

LVEF(< %) % %

% f ti n l

h t nin + +

Cardiac FunctionCardiac Function


53/68

What about his bones?What about his bones?


54/68

What makes bones healthy?What makes bones healthy?

Genetics

Physical activity

Other things: calcium, vitamin D etc


55/68

What about my sonsWhat about my sons

bones?bones?Even young have reduced bone density

Worse with reduced walking

~25% have long bone fractures

Vertebral (back bone) fractures dont occur


56/68

OsteoporosisOsteoporosis

Bisphosphonates (fosamax)

not approved for children

side-effects?

effective?

growing bone?


57/68

Osteoporosis StudyOsteoporosis Study

Summary

Alendronate (fosamax)

well tolerated

minimal side effects

improved lumbar spine bone density

not approved for children


58/68

Bottom LineBottom Line

More questions than answers

Most boys have osteoporosis

Why measure bone mineral density?

Does it help you manage boys better?

Does it predict the risk of fractures?


59/68

Bottom LineBottom Line

Probably worse with deflazacort

Risk of fractures, controversial

long bones vertebrae

Can be treated, if indicated

More research needed


60/68

Incidence of FracturesIncidence of FracturesIncidence of FracturesIncidence of Fractures

5%

10%

15%

20%

25%

Naples Toronto Control


61/68

Benefits of deflazacort appear to

outweigh side effects

ConclusionsConclusions

Majorbenefits of preserved: walking

pulmonary function

cardiac function straight spine

arm and hand function


62/68

CataractsCataracts

70% of boys after10 years

Small Eye sight normal

No treatment needed


63/68

Psychosocial IssuesPsychosocial Issues

difficult to know

we need more research

very, very important


64/68


Side effects:

weight height

cataracts

osteoporosis delayed puberty


65/68

No hypertension

No diabetes

No renal stones

No liver problems

No increased fractures



66/68

What dont we know?What dont we know?

Lots.

What age to start?

What is the best dose to start with? Does he have to take it every day?

What is the dose over the next years?

When, if ever, do you stop? What will happen if I stop steroids?


67/68

For more information:For more information:

Articles:Deflazacort Treatment of Duchenne Muscular Dystrophy:

Doug Biggar, et al.

Journal ofPaediatrics, 45 - 50, 2001.

Effects of Deflazacort on Left Ventricular Function in Patients With

Duchenne Muscular Dystrophy: Silversides C. et al.

American Journal of Cardiology, Vol. 91, 769, 2003.

Steroid Treatment and the Development ofScoliosis in Males with

Duchenne Muscular Dystrophy: Alman, B.A. et al.

Journal of Bone and Joint Surgery, Vol. 86, 519- 524, 2004

Long-term benefits of deflazacort treatment for boys with DMD in

their second decade: Doug Biggar, et al.

Neuromuscular Disorders, 16, 249-255, 2006.


68/68

Deflazacort Treatment in

Duchenne MuscularDystrophy

Parent Project MuscularDystrophyCincinnati, Ohio

July 2003

Doug Biggar, MD, FRCP(C)

Thank You!Thank You!

Parent Project July 2006v5

Documents

Transcript of Parent Project July 2006v5