With advances in available therapy failure to act when RRMS patients have active disease could be considered negligent

For: Robert Brenner

Against: Gavin Giovannoni

Gavin Giovannoni has provided consultation to Bayer-Schering Healthcare, Biogen-Idec, Genzyme, GlaxoSmithKline, Merck-Serono, Novartis, Protein Discovery Laboratories, Teva-Aventis, UCB Pharma, Ironwood, Eisai, Vertex, Roche, Synthon and Canbex. He has received grant support from Bayer-Schering Healthcare, Biogen-Idec, Merck-Serono, Merz, Novartis, Teva-Aventis, GW Pharma.

Disclosures

With advances in available therapy failure to act when RRMS patients have active disease could be considered negligent.

The Middlesex Hospital before it was sold.

The Middlesex Hospital now; vacant and derelict.

Our mentor; Dr Gerald Stern.

Medicolegal work; in particular malpractice work.

38yr old teacher with RRMS under the care of Dr B at a London Hospital

• Glatiramer acetate 3 years (good adherence)

• Relapse with a mild left sensory loss

• Referred to me for a second opinion

• Switched to interferon-beta (IM IFNbeta-1a; www.msdecisions.org.uk)

• Mild persistent flu-like side effects and lymphopenia

• 12/12 NAb screen negative

• Volunteers for new research programme, which included an MRI protocol

Teacher

DISCLAIMER: This is a fictitious case to illustrate a

medico-legal point

Teacher

38yr old teacher with RRMS

• Forced to retire due to cognitive impairment and severe fatigue

• Developed depression and anxiety

• In her spare time she becomes and expert patient

– Widely read

– Net savvy; regular follower of www.ms-res.org

DISCLAIMER: This is a fictitious case to illustrate a

medico-legal point

Unemployment

Pfleger et al. Multiple Sclerosis 2010; 16(1) 121–126. 13

Costs and quality of life of patients with MS in Europe

Kobelt et al. J Neurol Neurosurg Psychiatry 2006;77:918–926.

Bermel et al. Ann Neuol 2012.

Predictors of long-term outcome in MSers treated with interferon beta-a

Bermel et al. Ann Neuol 2012.

Predictors of long-term outcome in MSers treated with interferon beta-1a

MRI to monitor treatment response to IFNβ: a meta-analysis

Dobson et al. Submitted 2013.

Study or Subgroup Odds Ratio

IV, Random, 95% CI

Kinkel 2008

Prosperini 2009

Total (95% CI) 9.86 (2.33, 41.70)

Study or Subgroup Odds Ratio

IV, Random, 95% CI

Kinkel 2008

Pozzilli 2005

Prosperini 2009

Sormani 2011

Total (95% CI) 2.69 (0.72, 10.04)

0.01 0.1 1 10 100 Disease Less Likely Disease More Likely

One New T2 Lesion

Favors Experimental Favors Control

100 10 1 0.1 0.01

Two or More New T2 Lesions

Study or Subgroup Odds Ratio

IV, Random, 95% CI

Kinkel 2008

Rio 2008

Total (95% CI) 5.46 (2.48, 12.04)

MRI to monitor treatment response to IFNβ: a meta-analysis

Dobson et al. Submitted 2013.

Study or Subgroup Odds Ratio

IV, Random, 95% CI

Kinkel 2008

Pozzilli 2005

Tomassini 2006

Total (95% CI) 3.34 (1.36, 8.22)

0.01 0.1 1 10 100 Disease Less Likely Disease More Likely

One New Gd+ Lesion

0.01 0.1 1 10 100

Disease Less Likely Disease More Likely

Two or More New Gd+ Lesions

DISCLAIMER: This is a fictitious case to illustrate a medico-legal point

Guidelines for the prescribing of IFN-beta and GA

Fulfil the following 4 criteria:

1. Able to walk independently

2. At least two clinically significant relapses in the last two years

Where possible, the patient’s history of relapses should have been confirmed by neurological examination or from another source e.g. hospital or general practitioner’s records, or by discussion with the patient’s main carer.

3. Adult age group (18 years or older)

no recommendations are possible in the paediatric age group, since trials have not been performed in this cohort.

4. There are no contraindications

Association of British Neurologists Guidelines for the use of Beta Interferons and Glatiramer Acetate in MS, January 2001.

Guidelines for the prescribing of Natalizumab

Natalizumab is recommended as an option for the treatment only of rapidly evolving severe relapsing–remitting multiple sclerosis (RES). RES is defined by two or more disabling relapses in 1 year,

and one or more gadolinium-enhancing lesions on brain magnetic

resonance imaging (MRI) or a significant increase in T2 lesion load

compared with a previous MRI.

1st-line or naïve MSers or 2nd-line (IFN-beta or GA failures)

NICE - Natalizumab for the treatment of adults with highly active relapsing–remitting multiple sclerosis; August 2007.

Guidelines for the prescribing of Fingolimod

Fingolimod is recommended as an option for the treatment of highly active relapsing–remitting multiple sclerosis in adults, only if:

1. they have an unchanged or increased relapse rate or on-going severe relapses compared with the previous year despite treatment with beta interferon, and

2. the manufacturer provides fingolimod with the discount agreed as part of the patient access scheme.

NICE Fingolimod: final appraisal determination document; 16 March 2012 .

The relapsing MS DMT doughnut

Inactive RRMS

CIS

RIS or asymptomatic MS

Suboptimal responders ?

Active RRMS

IFNbeta or GA

IFNbeta

Highly active RRMS Fingolimod Natalizumab

Verdict: not negligent

Teacher

Dr B

DISCLAIMER: This is a fictitious case to illustrate a

medico-legal point

Teacher

Dr B

Choice of natalizumab or fingolimod on a private prescription

DISCLAIMER: This is a fictitious case to illustrate a

medico-legal point

With advances in available therapy failure to act when RRMS patients have active disease could be considered negligent.

Neurologist

Wife

What would you do if this was your wife

or husband?

Would you risk the wrath of the NICE

inspectors?

DISCLAIMER: This is a fictitious case to illustrate a

medico-legal point