1. Scottish Muscle Network AHP study day 20 th April 2015 Karen Naismith

2. North Star

3. 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

4. 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

5. North star assessment

8. 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; J Neurol Neurosurg Psychiatry. Ricotti VRidout DAScott EQuinlivan RRobb SAManzur AYMuntoni F Daily vs intermittent regimes 360 boys age 3-15 Loss of mobility 12 vs 14.5 Incidence and defined SE

9. British Paediatric Neurology Association Prevalence 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 NetworkNorthStar Clinical Network Defined vit D deficiency 157 boys 78% deficient 15% symptomatic

11. 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

12. North star network Challenging clinical questions Facilitate Research and Clinical trials Collective responses Access to audit

13. Scottish Muscle Network background 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Yorkhill NHS Trust University of Glasgow Orchid Ball Foundation Myotonic Dystrophy Support Group Yorkhill Muscle Fund Yorkhill Foundation Muscular Dystrophy Campaign National Services Division, Scottish Government

14. 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

15. 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

16. 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

17. DMD MD Care pathway 2009 Early/pre-symptomatic Early ambulant Late ambulant Early non-ambulant Late non-ambulant Palliative/end of life care

18. Young men > age 18 years living in Scotland

19. TREAT NMD DMD care standards

20. 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

21. 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

22. Thank you for listening!

23. 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 J Neurol Neurosurg Psychiatry. Ricotti VRidout DAScott EQuinlivan RRobb SAManzur AYMuntoni 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.

24. British Paediatric Neurology Association Prevalence 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 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.