The most recent analysis from the MSBase Study Group has examined how treatment decision-making affects the risk of conversion to secondary-progressive multiple sclerosis (SPMS) (Brown et al. JAMA 2019;321:175-187). The results indicate that starting with a higher-efficacy disease-modifying therapy (DMT) or switching earlier can substantially reduce the risk of SPMS.
The propensity score-matched cohort study included data from 1555 patients (mean age 35 years at baseline) treated at 68 neurology centres in the period 1988-2017. All patients had a minimum of four years of follow-up. Starting treatment with a front-line DMT (glatiramer acetate or beta-interferon) was associated with a 29% lower risk of conversion to SPMS compared to remaining untreated. The 5-year absolute risk of SPMS was 12% in treated versus 27% in untreated patients (median follow-up 7.6 years). There was also a benefit if a front-line therapy was initiated within five years of disease onset compared to later (hazard ratio 0.77); the absolute risk was 3% with treatment versus 6% without treatment over a median follow-up of 13.4 years.
The risk of SPMS was lower if treatment was initiated with fingolimod (HR 0.37), alemtuzumab (HR 0.52) or natalizumab (HR 0.61). The 5-year absolute risk of SPMS was 7% in the fingolimod cohort (vs. untreated 32%; median follow-up 4.5 years), 10% in the alemtuzumab cohort (vs. untreated 25%; median follow-up 7.4 years), and 19% in the natalizumab cohort (vs. untreated 38%; median follow-up 4.9 years).
In addition, starting treatment with a higher-efficacy DMT was associated with a significantly lower risk of SPMS compared to starting with a front-line therapy (HR 0.66). The 5-year absolute risk was 7% with a higher-efficacy therapy versus 12% with a front-line therapy (median follow-up 5.8 years).
Although the opportunities for starting treatment with a higher-efficacy therapy are limited in some countries due to product labelling, early escalation was shown to be an effective strategy. When patients on a front-line therapy were escalated to a higher-efficacy therapy within five years rather than after five years, there was a 24% reduction in the risk of conversion to SPMS. The 5-year absolute risk of SPMS was 8% with a higher-efficacy DMT versus 14% with a front-line therapy at a median follow-up of 5.3 years.