Scottish Muscle NetworkAHP study day

20th April 2015Karen Naismith

North Star

What is the North Star Network?

History of steroid debate Consideration of clinical trial Formation of UK national NM network

North star project supported by MDC

North star project- UK national NM database

Standardised information and data collection

Clinical assessments Outcomes Research and publications

Recommendations for best practice and management guidelines

North star assessment

Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy NORTH STAR CLINICAL NETWORK J Neurol Neurosurg Psychiatry. 2013 Jun;84(6):698-705. doi: 10.1136/jnnp-2012-303902. Epub 2012

Ricotti V1, Ridout DA, Scott E, Quinlivan R, Robb SA, Manzur AY, Muntoni F;

Daily vs intermittent regimes 360 boys age 3-15 Loss of mobility 12 vs 14.5 Incidence and defined SE

British Paediatric Neurology AssociationPrevalence of vitamin D deficiency in 157 boys with duchenne muscular dystrophyMunot1, D Krishnakumar1, S Robb1, T Davies1, F Muntoni1,2, A Manzur1 NorthStar Clinical Network

Defined vit D deficiency 157 boys 78% deficient 15% symptomatic

Journal of Neurology, Neurosurgery and Neuropsychiatry 2015

The North Star Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design

of clinical trials

Valeria Ricotti,1,3 Deborah A Ridout,2,3 Marika Pane,4 Marion Main,1,3 Anna Mayhew,5 Eugenio Mercuri,1,4 Adnan Y Manzur,1,3 Francesco Muntoni,1,3

on behalf of

UK North Star Clinical Network

North star network

Challenging clinical questions Facilitate Research and Clinical

trials Collective responses Access to audit

Scottish Muscle Network background

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Yorkhill NHS TrustUniversity of GlasgowOrchid Ball FoundationMyotonic Dystrophy Support GroupYorkhill Muscle FundYorkhill Foundation

Muscular Dystrophy Campaign

National Services Division, Scottish Government

Scottish Muscle Network MCN Paediatric subgroup Physiotherapy Transition group Adult DM1(neurology) Respiratory care Service users Training and education

Links with Arrythmia and Inherited cardiac conditions MCN

SMN 2008- paediatric medical Management of DMD Lead paediatrician Investigation & information Referrals to genetics/PT/OT Steroids Cardiac surveillance Spinal referral Immunisation Respiratory referral Transition

2011 DMD audit 102 boys 0-16 yrs

100% had lead paediatrician 91% referred to genetics 100% receiving PT 57% referred to OT 93% referred to spinal service 92% under cardiology review 92% under respiratory review 57% documented immunisation

DMD MD Care pathway 2009

Early/pre-symptomatic Early ambulant Late ambulant Early non-ambulant Late non-ambulant Palliative/end of life care

Young men > age 18 years living in Scotland

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TREAT NMD DMD care standards

SMN paediatric subgroup CMD FSH Bone health SMA endorsed

Information leaflets & after diagnosis packs

Database DMD & SMA

Clinical trials & research eg exon skipping and point mutation

FOR DMD Consensus views

eg Translerma

Spinal Audit- Retrospective case note review young adults with DMD > 16 years

Age referred to SS Age of surgery Age of discharge Evidence of

progression

Cardiac Rx NIV/IV Steroid therapy Education/

employment/ independent living

Thank you for listening!

Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy

J Neurol Neurosurg Psychiatry. 2013 Jun;84(6):698-705. doi: 10.1136/jnnp-2012-303902. Epub 2012

Ricotti V1, Ridout DA, Scott E, Quinlivan R, Robb SA, Manzur AY, Muntoni F; NorthStar Clinical Network

OBJECTIVE: To assess the current use of glucocorticoids (GCs) in Duchenne muscular dystrophy in the UK, and

compare the benefits and the adverse events of daily versus intermittent prednisolone regimens.

DESIGN: A prospective longitudinal observational study across 17 neuromuscular centres in the UK of 360

boys aged 3-15 years with confirmed Duchenne muscular dystrophy who were treated with daily or intermittent (10 days on/10 days off) prednisolone for a mean duration of treatment of 4 years.

RESULTS: The median loss of ambulation was 12 years in intermittent and 14.5 years in daily treatment; the

HR for intermittent treatment was 1.57 (95% CI 0.87 to 2.82). A fitted multilevel model comparing the intermittent and daily regiments for the NorthStar Ambulatory Assessment demonstrated a divergence after 7 years of age, with boys on an intermittent regimen declining faster (p<0.001). Moderate to severe side effects were more commonly reported and observed in the daily regimen, including Cushingoid features, adverse behavioural events and hypertension. Body mass index mean z score was higher in the daily regimen (1.99, 95% CI 1.79 to 2.19) than in the intermittent regimen (1.51, 95% CI 1.27 to 1.75). Height restriction was more severe in the daily regimen (mean z score -1.77, 95% CI -1.79 to -2.19) than in the intermittent regimen (mean z score -0.70, 95% CI -0.90 to -0.49).

CONCLUSIONS: Our study provides a framework for providing information to patients with Duchenne

muscular dystrophy and their families when introducing GC therapy. The study also highlights the importance of collecting longitudinal natural history data on patients treated according to standardised protocols, and clearly identifies the benefits and the side-effect profile of two treatment regimens, which will help with informed choices and implementation of targeted surveillance.

British Paediatric Neurology AssociationPrevalence of vitamin D deficiency in 157 boys with duchenne muscular dystrophy Munot1, D Krishnakumar1, S Robb1, T Davies1, F Muntoni1,2, A Manzur1

  NorthStar Clinical Network

Introduction: Boys with Duchenne muscular dystrophy (DMD) have low bone density. Although corticosteroids improve muscle strength and function in boys with DMD, potential adverse effects include osteoporosis and vertebral fractures. Bianchi et al1reported low Vitamin D levels in a small cohort of boys with DMD. The optimal 25-OH vitamin D levels in children have been redefined by Misra et al2 with the recommendation that serum 25-OH vitamin D level <37.5 nmol/litre constitutes vitamin D deficiency and a level greater than 50 nmol/l is indicative of sufficiency. In the UK no large studies to establish vitamin D levels in children with DMD.

Objectives: To establish the prevalence of vitamin D deficiency in boys with DMD.

Methodology: The North Star neuromuscular network consensus is to check vitamin D levels prior to starting corticosteroid therapy. Data on vitamin D levels was retrospectively collected from the case records through the north star neuromuscular database.

Results: 25-OH vitamin D levels were available in 157 boys with DMD. The mean age at checking vitamin D level was 6.9 years (1.5–15.5). Vitamin D levels ranged from 4–155 mol/litre.

Alkaline phosphatase was low or normal in all. Clinical rickets was not diagnosed in any of these boys. Among those with levels > 50 nmol/L, at least 2/28 were on supplements.

Conclusion: 78% of boys who were tested had inadequate vitamin D levels according to current standards and 15% had severe deficiency. These data have important implications for optimising bone health and for corticosteroid treatment in DMD.