OBJECTIVES: This was a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in MSers with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS).
METHODS: The MSBASIS Study, conducted by MSBase Study Group members, enrols MSers seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. A multivariable survival analysis was performed to determine factors within this dataset that predict first treatment discontinuation.
RESULTS: A total of 2314 MSers with CIS from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status.
- Over 40% of these MSers stopped their first IMD during the observation period.
- Females were more likely to cease medication than males (HR 1.36, p = 0.003). MSers treated in Australia were twice as likely to cease their first IMD than MSers treated in Spain (HR 1.98, p = 0.001).
- Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries.
- Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation.
CONCLUSION: In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation.
“This study looks at features that appear to determine adherence to your exisiting medication; a 40% discontinuation rate is very worrying. The aim of DMTs is to prevent relapses and focal areas of inflammation and by doing this prevent the accumulation of disability in the longterm. If MSers stop taking their drugs this strategy falls down at stage one. People think the emergence of oral therapies will sort this problem out. I am not so sure. I think this is an education issue. In our first audit, at the National Hospital for Neurology and Neursurgery, we had adherence rates of over 95% at 2 years and even in the 5% who had stopped taking their DMT we had a reason for it. I suspect MSers in this study were not receiving the necessary information and assistance when starting DMTs to persist with the treatment.”
“What is the point showing that IFNbeta has a positive impact on clinical course at 16 years and survival at 21 years when 40% of MSers are off the drugs at 2.7 years? We have a problem!”
“Are you all adherent with your medication? If not, please let us know why?”