Effectiveness of first generation disease-modifying therapy to prevent conversion to secondary progressive multiple sclerosis

•Incidence of conversion to SPMS decreased markedly in Sweden after 1995.•First generation disease modifying drugs were introduced in Sweden by 1995.•We observed consecutive untreated and treated cohorts, and a calendar year function.•Using population cohorts reduced indication bias, and inclusion bias was considered.•Introduction of disease-modifying drugs probably reduced conversion to SPMS. The use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) has been associated with reduced relapse rates and accumulation of disability. However, studies examining impact of DMT on risk of transition to secondary progressive MS (SPMS) leveraging population-based nationwide data are still rare. Here, we determine the population incidence of conversion to SPMS using two consecutive nation-wide cohorts, one immediately before and one after the introduction of DMT in Sweden. We included two consecutive population cohorts of relapsing-remitting MS (RRMS) from the Swedish national MS register for the periods 1975–1994 (n = 2161), before DMT availability, and 1995–2011 (n = 3510), in which DMTs, mainly first generation DMT (injectables), became available and eventually were used by 70% of patients. We explored the risk of transition to SPMS as a calendar year function encompassing the two cohorts. In addition, we determined the incidence of transition to SPMS through age strata below and above 50 years in untreated and treated patient subgroups. The risk of conversion to SPMS (adjusted for current age, current time since onset, calendar year and sex) was significantly lower in the second compared with the first population cohort (hazard ratio 0.58; CI 0.48, 0.70). The risk of SPMS conversion per calendar year decreased by 2.6% annually (p < 0.001) after 1995. The risk of SPMS conversion increased with age until age 50. Thereafter, it was unchanged or decreased among those with early MS onset age (