To those who insist the side effects of MS drugs are worse than the treatments themselves, science says otherwise. Being on a DMT, especially a newer one, makes a significant difference. -D

Estimating the long-term effect of drugs in multiple sclerosis

C. Cordioli1, S. Rasia1, F. Gallo2, R. Capra1, M.P. Sormani2 1Multiple Sclerosis Centre, Spedali Civili, Montichiari, 2Section of Biostatistics, Department of Health Sciences (DISSAL), University of Genoa, Genova, Italy

Background: In multiple sclerosis (MS) there is no certainty to what extent the short-term effects of drugs translate into long-term benefits for patients. Observational studies devoted to clarify this issue are affected by selection bias: treated and untreated patients are different and their difference is likely related to prognosis.

Goals: To evaluate whether the introduction of therapies changed the MS prognosis, assessing the age at which patients diagnosed in different periods (pre and post therapies approval) reached EDSS milestones, with no comparisons of treated and untreated patients.

Methods: We retrospectively analysed a large dataset of MS outpatients evaluated at the MS Centre of Montichiari (Brescia, Italy) between 1985 and 2013, with an initial RRMS course and age at diagnosis 18-60 years. Age at which patients reached EDSS 6 was compared according to year of diagnosis (grouping patients diagnosed in 1980-1990, 1991-1995, 1996-2000, 2001-2005, 2006-2010, 2011+), by a Cox model adjusted for mean age at diagnosis and EDSS visits frequency.

Results: 1324 RRMS patients were included. The average age at onset was 32.4 years (SD= 9.6, range =13-59 years) and the average age at diagnosis was 35.6 years (SD= 10.0, 18-60 years). The age at diagnosis increased from 32 to 37 years (p< 0.001) in more recent years. Patients diagnosed in more recent periods reached EDSS=6 at higher age: taking patients diagnosed before 1990 as a reference, the probability to reach EDSS=6 was similar in patients diagnosed in the period 1991-1995 (HR=1.09), it was reduced by 15% in patients diagnosed in 1996-2000 (HR=0.85, p=0.44), by 37% in patients diagnosed in 2001-2005 (HR=0.63, p=0.05), by 46% in patients diagnosed in 2006-2010 (HR=0.54, p< 0.02). The proportion of patients diagnosed before 2000 who reached EDSS=6 at the age of 50 years was 27% and 15% after 2000 (p< 0.001).

Conclusions: A clear modification of MS course is observed after 2000, with 4 years delay since 1996 (introduction of first DMTs in Italy), when the proportion of patients steadily treated was increasing. A second leap coincides with the introduction of second-line treatments (natalizumab, fingolimod).