1. From Compliance to Adherence can todays situation improve ? EMSP Information Day Brussels, 13 November 2008 Magnhild Sandberg-Wollheim

2. M Sandberg 2008-11-13 Why are patients with MS not compliant?

3. M Sandberg 2008-11-13 Prognosis of MS yesterday 35 years ago two young men were diagnosed with optic neuritis – 35 years ago two young men were diagnosed with optic neuritis – –a common first symptom of MS At that time, At that time, –we had no prognostic markers –we had no Disease Modifying Treatments So what has happened? So what has happened?

4. M Sandberg 2008-11-13 Prognosis of MS yesterday One of them One of them –never had another attack and has remained healthy The other man The other man –had several attacks over the next few years –eventually needed a wheelchair to move around –and became tetraplegic

5. M Sandberg 2008-11-13 Prognosis of MS today We still have no prognostic markers We still have no prognostic markers We still have no cure, BUT We still have no cure, BUT We do have DMTs We do have DMTs So why are patients not compliant So why are patients not compliant –the disease is not an immediate threat –but we know from natural history studies that 50% will have progressive disease after ~15 yrs

6. M Sandberg 2008-11-13 Adherence to long-term therapy For chronic illnesses in developed countries adherence is only ~50% For chronic illnesses in developed countries adherence is only ~50% Non -adherence rates in Non -adherence rates in –diabetes 36-87% –hypertension 33-84% –cancer (oral drugs) 20-100%

7. M Sandberg 2008-11-13 Increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments Increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments Haynes RB et al. Haynes RB et al. Cochrane Database Syst Rev 2005;4:CD000011

8. M Sandberg 2008-11-13 Definition of Adherence WHO 2003 The extent to which a persons behaviour – taking medication, following a diet, and/or executing lifestyle changes – corresponds with agreed recommendations from a healthcare provider The extent to which a persons behaviour – taking medication, following a diet, and/or executing lifestyle changes – corresponds with agreed recommendations from a healthcare provider Adherence to Long-term Therapies: Evidence for Action, WHO 2003, ISBN 92 4 154599 2 www.emro.who.int/ncd/Publications/adherence_report.pdf

9. M Sandberg 2008-11-13 Adherence vs Compliance WHO 2003 Adherence Adherence –requires that patient has agreed with treatment recommendations –stresses that patient has a choice of whether or not to follow treatment recommendations –is preferred to compliance as this implies that the patient is passive in decision-making processes

10. M Sandberg 2008-11-13 Consequences of poor treatment adherence Treatment outcomes will be poor in the short term Treatment outcomes will be poor in the short term –may negatively affect adherence, resulting in a vicious circle Disease sequelae in the long term Disease sequelae in the long term High health-care costs High health-care costs –patients with severe disability are costly

11. M Sandberg 2008-11-13 What is the cost in money?

12. MS: Low Prevalence Compared to other disorders of the brain - 5 10 15 20 25 30 35 40 45 Number of cases (million) Anxiety disorders Migraine Affective disorders Addiction Dementia Psychotic disorders Epilepsy Parkinson's disease Stroke Trauma Multiple Sclerosis Brain tumour Source: Sobocki et al, Eur J Neurology 2005;12(S1)

13. MS: High Cost per Patient Compared to other disorders of the brain 0 5 000 10 000 15 000 20 000 25 000 30 000 35 000 40 000 Cost per patient ( 2004) tumour multiple sclerosis stroke dementia psychotic disorders parkinson epilepsy affective disoders trauma addiction anxiety disorders migraine Source: Sobocki et al, Eur J Neurology 2005;12(S1)

14. Cost of MS in Sweden in 2005 Results – Cost by severity (N=1339) Source: Berg J, Lindgren P, Fredrikson S, Kobelt G. Eur J Health Economics 2006;7(S2):77-87

15. M Sandberg 2008-11-13 Existing DMDs for MS Self-injectables Self-injectables –interferon beta (IFNβ), glatiramer acetate (GA) –intramuscular or subcutaneous –daily, every other day, thrice weekly, once weekly Hospital injections Hospital injections –natalizumab (and mitoxantrone off-label) –intravenous –every four weeks (or every three months)

16. M Sandberg 2008-11-13 Factors with a negative effect on adherence to treatment Needle phobia or anxiety Needle phobia or anxiety –is present in approx 10-20% of the population –is more common with self-injections –may need to involve family or friends or healthcare providers Difficulty with administration Difficulty with administration –reduced manual dexterity –cognitive impairment Time needed for administration Time needed for administration –from daily to weekly regimens Cohen & Rieckmann Int J Clin Pract 2007;61:1922–30

17. M Sandberg 2008-11-13 Factors with a negative effect on adherence to treatment Injection site reactions Injection site reactions –pain, bruising, infiltrates, abscesses Adverse effects Adverse effects –fever, influenza like symptoms, headache –liver and thyroid function tests abnormal –depression –fatigue Disruption of life-style Disruption of life-style Unrealistic expectations Unrealistic expectations Cohen & Rieckmann. Int J Clin Pract 2007;61:1922–30

18. M Sandberg 2008-11-13 What happens in clinical practice?

19. M Sandberg 2008-11-13 In clinical practice 9-20% discontinue treatment in the first 6 months 9-20% discontinue treatment in the first 6 months ~40% do not restart therapy ~40% do not restart therapy

20. Discontinuation of existing DMDs in clinical practice DMD, disease-modifying drug; GA, glatiramer acetate; IFN, interferon 1 Tremlett HL, Oger J. Neurology 2003;61:551–4 2 ORourke KET, Hutchinson M. Mult Scler 2005;11:46–50 3 Rio J et al. Mult Scler 2005;11:306–9 >3 years follow up 1 4 years follow up 3 4 years follow up 2 IFN beta 0 10 20 30 40 IFN betaIFN beta or GA Discontinuation rate (%) 39% (79/203) 17% (107/622) 28% (109/394) Courtesy Merck Serono

21. Reasons for discontinuation of IFN beta 30% 12% 10% 9% 8% 7% 6% 0 5 10 15 20 25 30 Perceived lack of efficacy Injection- site reactions Flu-like symptoms DepressionHeadacheLiver test abnormalities Fatigue Patients (%) giving that reason for interruption of >1 month IFN, interferon Tremlett HL, Oger J. Neurology 2003;61:551–4 Perceived lack of efficacy and occurrence of side-effects were the main reasons cited by patients who discontinued IFN beta therapy Courtesy Merck Serono

22. M Sandberg 2008-11-13 What is needed? Patient education Patient education –about the disease ongoing but subclinical disease ongoing but subclinical disease no marker for disease activity no marker for disease activity –about the treatments are partially effective are partially effective patients must have realistic expectation patients must have realistic expectation make patients feel worse, not better make patients feel worse, not better occurrence of a relapse is expected but undermines patients confidence in the treatment occurrence of a relapse is expected but undermines patients confidence in the treatment

23. M Sandberg 2008-11-13 What more is needed? Treatments with improved tolerability and safety Treatments with improved tolerability and safety –IFNβ and GA have good safety profile have good safety profile have not so good tolerability have not so good tolerability –natalizumab (and mitoxantrone off-label) have good tolerability have good tolerability have not so good safety profile have not so good safety profile –oral agents and other new agents safety is perhaps going to be a concern based on the mechanism of action of some safety is perhaps going to be a concern based on the mechanism of action of some

24. M Sandberg 2008-11-13 What is really needed? Treatments with improved efficacy Treatments with improved efficacy –agents that stop relapses and progression including agents for SPMS and PPMS including agents for SPMS and PPMS –agents that are neuroprotective and reverse the disease process –agents that are curative!

25. M Sandberg 2008-11-13 End