1. DoH IVIG Workshop Update, neurology usage and outcomes measurement
Dr Michael Lunn
National Hospital for Neurology and Neurosurgery
Queen Square, London WC1N 3BG

2. Outline Neurology IVIG usage update
Neurology in 2011 Guidelines Update
Measuring outcomes
Update guidelines
Measuring outcomes in clinical practice
What’s wrong with what we are using
How can we make it better?

3. IVIG in Neurology Usage update

6. Neurology Infusions by Diagnosis 01/04/2010 - 31/03/2011
Grams Used
% Of Total
Chronic inflammatory demyelinating polyradiculoneuropathy 
48.33%
Multifocal motor neuropathy 
22.89%
Guillain–Barré syndrome
9.98%
Myasthenia gravis 
7.06%
Other (Neurology) 
45410
4.63%
Other (Other) 
1.19%
Paraprotein-associated demyelinating neuropathy (IgM) 
Stiff person syndrome 
10255
1.05%
Paraprotein-associated demyelinating neuropathy (IgG or IgA) 
7969
0.81%
Paraneoplastic disorders 
5196.5
0.53%
Acute disseminated encephalomyelitis 
3902.5
0.40%
Polymyositis 
3580
0.37%
Lambert Eaton myasthenic syndrome 
3215
0.33%
Vasculitic neuropathy 
2735
0.28%
Rasmussen syndrome 
2215
0.23%
Neuromyotonia 
1380
0.14%
Multiple sclerosis 
1330
Critical illness neuropathy 
1145
0.12%
CNS vasculitis 
730
0.07%
Inclusion body myositis 
600
0.06%
Bickerstaff's brain stem encephalitis 
510
0.05%
Chronic fatigue syndrome 
442.5
Dermatomyositis 
370
0.04%
Autism 
360
Acute idiopathic dysautonomia 
175
0.02%
Autoimmune diabetic proximal neuropathy 
110
0.01%
94.89%

7. Neurology Patients by Diagnosis 01/04/2010 - 31/03/2011
% Of Total
Chronic inflammatory demyelinating polyradiculoneuropathy 
854
34.24%
Guillain–Barré syndrome
633
25.38%
Multifocal motor neuropathy 
353
14.15%
Myasthenia gravis 
296
11.87%
Other (Neurology)  93
3.73%
Other (Other)  62
2.49%
Paraneoplastic disorders  27
1.08%
Paraprotein-associated demyelinating neuropathy (IgM) 
Stiff person syndrome 
Acute disseminated encephalomyelitis  21
0.84%
Paraprotein-associated demyelinating neuropathy (IgG or IgA)  16
0.64%
Polymyositis  15
0.60%
Rasmussen syndrome  10
0.40%
Vasculitic neuropathy 
Lambert Eaton myasthenic syndrome  9
0.36%
Multiple sclerosis  8
0.32%
Neuromyotonia  6
0.24%
CNS vasculitis 
Critical illness neuropathy  5
0.20%
Bickerstaff's brain stem encephalitis 
Chronic fatigue syndrome  3
0.12%
Inclusion body myositis 
Intractable childhood epilepsy  1
0.04%
Dermatomyositis 
Acute idiopathic dysautonomia 
Autism 
Autoimmune diabetic proximal neuropathy 

8. How inclusive is the database data now?
In 2009 PASA estimated only 60% data capture
GBS cases
per
cases
60% require Rx
In GBS pts in database
Thus ?48 – 60% capture
In 2010 – 633 cases ?almost complete – 90%?
90.7% capture

9. Guidelines update

10. This update did not review all of the Second Edition Guidelines content, but limited its focus to three key areas
defining selection criteria for appropriate use;
efficacy outcomes to assess treatment success;
reassignment of existing indications /inclusion of new indications.

11. Reassignment of existing indications /inclusion of new indications.

12. ‘Grey’ diagnosis usage 2009
Red
Blue: long term
Blue: short term
Grey: long term
Grey: short term
Exceptionality
Not approved (rejected)
Awaiting panel decision
Panel decision not recorded
Acute disseminated encephalomyelitis  2 8 1
Acute idiopathic dysautonomia 
Bickerstaff's brain stem encephalitis  3
Intractable childhood epilepsy 
Paraneoplastic disorders  4
Polymyositis  10 5
Vasculitic neuropathy 
Other (Neurology)  7 20 14 23 6 13

13. 2009 24 patients with polymyositis Some life threatening
>50% approved
Polymyositis likely to be immune mediated
IBM (previously black)
2 cases only approved as exceptionality
Not infrequently ‘inflammatory’

14. Myositis criteria
Diagnosis of myositis by a neurologist, rheumatologist, immunologist of:
Patients with PM or DM who have significant muscle weakness;
OR Dysphagia and have not responded to corticosteroids and other immunosuppressive agents;
OR Patients with IBM who have dysphagia affecting nutrition (NOT patients with rapidly progressive IBM)
Outcomes and test dosage schedule suggested

15. Grey indications - changes
Immune-mediated disorders with limited evidence of immunoglobulin efficacy
Presumed immune-mediated disorders with little or no evidence of efficacy

16. Immune-mediated disorders with limited evidence of immunoglobulin efficacy
Acute disseminated encephalomyelitis
Autoimmune encephalitis (including NMDA and VGKC antibodies, among others)
Cerebral infarction with antiphospholipid antibodies
Chronic regional pain syndrome
CNS vasculitis
Intractable childhood epilepsy
Neuromyotonia
Opsoclonus Myoclonus

17. Immune-mediated disorders with limited evidence of immunoglobulin efficacy
Acute disseminated encephalomyelitis
Autoimmune encephalitis (including NMDA and VGKC antibodies, among others)
Cerebral infarction with antiphospholipid antibodies
Chronic regional pain syndrome
CNS vasculitis
Intractable childhood epilepsy
Neuromyotonia
Opsoclonus Myoclonus

18. Autoimmune encephalitis (including NMDA and VGKC antibodies, among others) and neuromyotonia
Granerod J et al 2009 – Lancet Infectious Disease
203 patients with encephalitis in UK in
42% infectious, 21% autoimmune, 37% unknown
16 case reports and small series of IVIG responsive Ab-mediated encephalitis since 2009

19. Complex Regional Pain Syndrome
Goebel A, Baranowski A, Maurer K, Ghiai A, McCabe C, Ambler G.
Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial.
Ann Intern Med Feb 2;152(3):152-8.

20. Presumed immune-mediated disorders with little or no evidence of efficacy
Acute idiopathic dysautonomia
Diabetic proximal neuropathy
PANDAS
Paraneoplastic disorders that are known not to be B- or T-cell mediated
POEMS

21. There remain rare disorders….

22. Efficacy outcomes to assess treatment success

23. Measuring outcomes: Current practice, potential and future possibilities
‘This update provides efficacy outcomes to be measured in all indications…. Efficacy outcomes are expected to play an important role in the IAP decision-making process for patients……This change reflects the wider change of focus in the NHS to patient outcomes, as presented in The NHS Outcomes Framework.’